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Aging Induced Proteinopathy in Neurodegenerative Disease: From Human to Worm (and back again?)

Brian C. Kraemer, PhD
Research Assistant Professor
UW Medicine Gerontology
University of Washington

Wednesday, May 29, 2013 - 4:30 PM
Health Sciences Center, Room T-739

Faculty Sponsor: Bill Mahoney, PhD

Why Attend?
Decreased turnover of proteins characterizes aging cells. Vulnerability to proteostatic impairment impacts neurons in particular and leads to misfolded and aggregated protein deposits. Lesions composed of protein aggregates such as the amyloid plaque and neurofibrillary tangle in Alzheimer’s disease as well as ubiquitinated inclusions in amyotrophic lateral sclerosis and frontotemporal lobar degeneration are the diagnostic neuropathological hallmarks of these diseases. The Kraemer lab uses simple C. elegans and cellular models of neurodegenerative protein aggregation disorders to identify candidate neuroprotective strategies for neurodegenerative. We are making progress towards our ultimate goal of finding small molecule inhibitors effective at reducing protein aggregate associated neuropathology and neuronal dysfunction in intact the mammalian brain.

Therapeutic Liver Repopulation: Can Cells Replace Organ Transplantation?

Markus Grompe, MD
Professor
Departments of Pediatrics and Molecular and Medical Genetics
Oregon Health & Science University

Wednesday, June 5, 2013 - 4:30 PM
Health Sciences Center, Room T-739

Faculty Sponsor: Ray Monnat, MD

Why Attend?
Dr. Grompe will present the first Nelson Fausto Lecture in recognition and honor of Dr. Fausto, Professor and Chair, UW Medicine Pathology, 1994-2011.

The Grompe Lab works on liver biology with a particular interest in therapeutic applications of liver cell transplantation. In this talk Dr. Grompe will provide an update on our current understanding of hepatic stem cell biology, and the unique properties of hepatocytes in terms of their replicative potential and adaptability. The prospect of replacing orthotopic liver transplantation with liver cell transplanatation will also be discussed.

Mutational Patterns of Mitochondrial DNA - Implications for Aging and Disease

Scott Kennedy, PhD
Post-Doc
Loeb Lab, UW Medicine Pathology
University of Washington

Wednesday, June 12, 2013 - 4:30 PM
Health Sciences Center, Room T-739

Faculty Sponsor: Larry Loeb, MD, PhD

Why Attend?
We all age, but the fundamental drivers of aging and its associated pathologies are poorly understood. The accumulation of mutations in mitochondrial DNA (mtDNA), thought to be primarily due to oxidative damage, has long been hypothesized to be to be a major driver of the aging process. However, these hypotheses have been difficult to test due to an absence of sensitive methods to detect rare mutations. Dr. Kennedy has pioneered the use of massively parallel sequencing technology to detect low frequency mutations. His seminar will focus on the use of these new methods to answer fundamental questions about mutagenesis in mtDNA, as well as his recent observations of mutation patterns that develop during human aging. His findings call into question a number of basic assumptions about the role of oxidative damage to mtDNA in aging and neurodegenerative diseases and has important implications in our understanding of the etiologies of these processes.

Genetic Studies of Erythropoiesis: From Erythrodysplasia to Leukemia

Keith Loeb, MD, PhD
Assistant Professor, UW Medicine Pathology
Assistant Member, Clinical Research Division
Fred Hutchinson Cancer Research Center

Wednesday, May 15, 2013 - 4:30 PM
Health Sciences Center, Room T-739

Faculty Sponsor: Marshall Horwitz, MD, PhD

Why Attend?
The decision to divide or differentiate is a fundamental question that underlies stem cell biology, developmental regulation, and tumorigenesis. Keith Loeb’s lab studies the impact of abnormal cell cycle regulation on stem cell maintenance and cellular differentiation focusing on hematopoiesis. This seminar will discuss studies of ineffective erythropoiesis as a consequence of cell cycle misregulation driven by mutant cyclin E. This model shares functional and morphologic similarities present in human myelodysplastic syndrome. He will also focus on results from a Sleeping Beauty transposon-mediated insertional mutagenesis study that further inhibited erythropoietic maturation resulting in erythroleukemia.

The Role of Dopamine Neurons in Mediating Cognitive Behaviors

Martin Darvas, PhD
Senior Fellow
Department of Biochemistry
University of Washington

Wednesday, May 8, 2013 - 4:30 PM
Health Sciences Center, Room T-739

Faculty Sponsor: Tom Montine, MD, PhD

Why Attend?
Parkinson's disease (PD) is a prevalent neurodegenerative disease and the number of cases is expected to double over the next 25 years in the U.S. Although best known for its characteristic movement disorder, PD is now appreciated to cause cognitive and psychiatric symptoms. PD is characterized classically by a loss of neurons in midbrain dopaminergic (DA) nuclei which leads to the hallmark motor symptoms of the disease and potentially contributes to cognitive impairment. Although traditional thinking attributed PD symptoms to loss of DA signaling resulting from DA neuronal cell loss, in reality a number of processes may contribute to the symptoms of PD. Dr. Darvas uses a combination of mouse genetics, viral gene transfer and neurotoxins together with tests designed to measure PD-relevant cognitive behaviors in mice to differentiate the contributions of DA vs. loss of DA neurons towards cognition.

Dissecting the Genetic Vascular Syndromes: From the Clinic to the Lab and Back Again

Mitzi Murray, MD, MA
Acting Assistant Professor
Department of Pathology
University of Washinton School of Medicine

Wednesday, May 1, 2013 - 4:30 PM
Health Sciences Center, Room T-739

Faculty Sponsor: Peter Byers, MD

Why Attend?
In the last decade, the molecular understanding of genetic syndromes conferring a high risk for arterial aneurysms, dissections and ruptures has greatly expanded. The journey of discovery begins with recognizing unique families to facilitate gene identification, then taking that knowledge back to the clinic to expand the phenotypic spectrum. Along the way, opportunities arise to better understand the pathophysiology of these types of vascular complications. Using cases, Dr. Murray will walk us through the characterization of these syndromes, what they teach us about vascular biology, ways to link pathology to genotype, how the testing works, and how this information can be used to provide better care for affected families.

Tumor Derived Lactate Dehydrogenase Drives Innate Immune Cell Crosstalk in Patients with Glioblastoma

Courtney Crane, PhD
Assistant Professor, UW Medicine Neurological Surgery
Principal Investigator, Ben Towne Center for Childhood Cancer Research
Seattle Children's Research Institute

Wednesday, April 24, 2013 - 4:30 PM
Health Sciences Center, Room T-739

Faculty Sponsor: Bill Mahoney, PhD

Why Attend?
The Crane Lab is a new lab at the Ben Towne Center for Childhood Cancer Research at Seattle Children's Research Institute. Our lab seeks to develop new immune therapies for patients with brain tumors. Our mission is to improve T cell based immune therapies using 'complete immune system' engineering. We plan to capitalize on the natural recruitment of tumor infiltrating myeloid cells (TIMC) to restructure the tumor microenvironment and improve the function of infiltrating innate and adaptive immune cells. Using an unbiased biochemical approach, we have identified a tumor derived enzyme which influences the crosstalk between TIMC and NK cells, and in doing so have identified new targets for immune therapy and biomarker development. Our recent data and long term goals will be discussed in this seminar.

Old Dog, New Trick: ERCC1 Expression as a Prognostic/Predictive Marker in Head and Neck Squamous Cell Carcinoma

Melissa C. Austin, MD
Resident
Department of Pathology
University of Washington

Wednesday, April 10, 2013 - 4:30 PM
Health Sciences Center, Room T-739

Faculty Sponsor: Rod Schmidt, MD, PhD

Why Attend?
Cisplatinum-radiotherapy is the backbone of treatment for non-resectable squamous cell carcinomas of the head and neck, but the addition of cisplatinum to radiotherapy adds significant toxicity for limited survival benefit; consequently, identification of surrogate markers of cisplatinum resistance has significant clinical importance. Determination of Excision Repair Cross-Complementation Protein 1 (ERCC1) expression by immunohistochemical techniques showed early promise as a surrogate for cisplatinum resistance, but its use has been plagued by inconsistent study associations using the original 8F1 antibody. Multiple new ERCC1 clones have become commercially available, so we sought to determine whether these new antibodies would perform more reliably and potentially generate a clinically useful cutpoint for patient stratification.

RB Collaborators in Cancer

David MacPherson, PhD
Assistant Member
Human Biology Division
Fred Hutchinson Cancer Research Center

Wednesday, April 3, 2013 - 4:30 PM
Health Sciences Center, Room T-739

Faculty Sponsor: Kelly Smith, MD, PhD

Why Attend?
The MacPherson lab uses genomic analyses and mouse modeling to understand two tumor types that harbor frequent RB mutations, retinoblastoma and small cell lung cancer (SCLC). Retinoblastoma is a genetically simple RB-deleted tumor type with few mutations beyond RB inactivation. Small cell lung cancer (SCLC) is the most aggressive type of lung cancer and is genetically complex. We apply genomic analyses of human samples as well as mouse models to identify genes that undergo recurrent mutation in SCLC. With the use of sensitized mouse models, candidate drivers are probed for tumor suppressor or oncogenic activity. This talk will describe our ongoing efforts to identify and understand the major drivers of retinoblastoma and SCLC.

Genetic Engineering of Human Pluripotent Stem Cells

David W. Russell, MD, PhD
Professor and Investigator of the Markey Molecular Medicine Center
Department of Medicine, Division of Hematology
University of Washington School of Medicine

Wednesday, March 27, 2013 - 4:30 PM
Health Sciences Center, Room T-739

Faculty Sponsor: Mike Laflame, MD, PhD

Why Attend?
Human pluripotent stem cells are being developed both as a source of cells to be used in regenerative medicine, and as cellular models of human diseases. For most of these applications, the cells will need to be genetically engineered. Dr. Russell will describe his research on precise gene targeting methods that can be used to genetically engineer these stem cells. He will present data showing the targeting of collagen gene mutations in iPSCs from patients with Osteogenesis Imperfecta, the removal of an extra copy of chromosome 21 from Down Syndrome iPSCs, and the creation of HLA-engineered universal donor stem cells.

Pathology in a Resource-limited Setting: A Resident's Experience in Kenya

Nadia V Giannakopoulos, MD
Surgical Pathology Fellow, AP Chief Resident
Department of Pathology
University of Washington School of Medicine

Wednesday, March 20, 2013 - 4:30 PM
Health Sciences Center, Room T-739

Faculty Sponsor: Rochelle Garcia, MD

Why Attend?
Learn about a resident's experience volunteering in a pathology department in a rural Kenyan hospital which serves as the pathology laboratory for 50 mission hospitals in Eastern Africa. Dr. Giannakopoulos spent a month at this hospital; she will discuss the differences in incidence and prevalence of disease between Kenya and the United Sates, the limitations of providing pathology services in resource-limited settings and show examples of some of the cases along with describing through words and pictures life in the hospital and surrounding area.

Mast Cell "goodness" in Innate Immunity

Adrian M. Piliponsky, Ph.D.
Assistant Professor
Center for Immunity and Immunotherapies
Seattle Children's Research Institute

Wednesday, March 13, 2013 - 4:30 PM
Health Sciences Center, Room T-739

Faculty Sponsor: Mark Majesky, PhD

Why Attend?
Mast cells are derived from hematopoietic progenitor cells and are widely distributed in tissues, especially at their interface with the external environment. Traditionally, mast cells and their mediators have been considered "pro-inflammatory" and therefore detrimental to the host during certain disorders, especially those associated with IgE-immune responses like asthma. Dr. Piliponsky's research departs from this dogma and instead aims to elucidate the beneficial mechanisms by which mast cells and mast cell-specific proteases contribute to homeostasis by regulating the host inflammatory response during bacterial infections. Dr. Piliponsky will discuss findings that reveal how mast cell proteases can protect against exogenous peptides contained in venoms as well as endogenous peptides and pro-inflammatory mediators generated during sepsis. Dr. Piliponsky will also provide an overview of the current and new genetic approaches used to examine the role of mast cells in health and disease.

Selection and Adaptation During Metastatic Cancer Progression

Christoph Klein, MD, PhD
Professor and Chair
Experimental Medicine and Therapy Research
University of Regensburg

Wednesday, March 6, 2013 - 4:30 PM
Health Sciences Center, Room T-739

Faculty Sponsor: Larry Loeb, MD, PhD

Why Attend?
A major cause of death from common cancers such as breast, prostate, and esophagus is metastases. Our speaker, Dr. Christoph Klein, has provided strong evidence that each of these human cancers metastasize early in their development, even before clinical detection. Dr. Klein and his group have pioneered methods to detect mutations and gene expression in single metastatic tumor cells. They determined that these disseminated cells differ markedly from the primary tumor with respect to point mutations, rearrangements and gene expression. These single cells can remain dormant for many years, but then proliferate and serve as founders for late cancer recurrence. His work on disseminated cancer cells and early metastatic progression is extremely important in guiding the development of therapies that target cancer metastases and dormant tumor cells.

Physiologic Control of Intestinal Stem Cells in Regeneration and Cancer

Omer Yilmaz, MD, PhD
Clinical and Research Fellow in GI Pathology
Massachusetts General Hospital
Harvard Medical School

Wednesday, February 27, 2013 - 4:30 PM
Health Sciences Center, Room T-739

Faculty Sponsor: Tom Montine, MD, PhD

Speaker is a faculty candidate in Pathology

Clonal Mosaicism for Large Chromosomal Anomalies from Birth to Old Age and its Relationship to Cancer

Cathy Laurie, PhD
Senior Principal Scientist
Department of Biostatistics
University of Washington School of Public Health

Wednesday, February 20, 2013 - 4:30 PM
Health Sciences Center, Room T-739

Faculty Sponsor: Christine Disteche, PhD

Why Attend?
Clonal mosaicism for large chromosomal anomalies (duplications, deletions and uniparental disomy) was detected using SNP microarray data from over 50,000 subjects recruited for genome-wide association studies. This detection method requires a relatively high frequency of cells (>5-10%) with the same abnormal karyotype (presumably of clonal origin) in the presence of normal cells. The frequency of detectable clonal mosaicism in peripheral blood is low (<0.5%) from birth until 50 years of age, after which it rises rapidly to 2-3% in the elderly. Many of the mosaic anomalies are characteristic of those found in hematological cancers and identify common deleted regions that pinpoint the locations of genes previously associated with hematological cancers. Although only 3% of subjects with mosaicism had any record of hematological cancer prior to DNA sampling, those without a prior diagnosis have an estimated 10-fold higher risk of a subsequent hematological cancer (95% confidence interval = 6-18).

Cellular Model-systems of Neurodegeneration

Subhojit Roy, MD, PhD
Assistant Professor
Departments of Pathology & Neurosciences
University of California San Diego, School of Medicine

Wednesday, February 13, 2013 - 4:30 PM
Health Sciences Center, Room T-739

Faculty Sponsor: Tom Montine, MD, PhD

Why Attend?
The Roy lab is generally interested in the cell biology of neurodegeneration. Though many key players involved in neurodegenerative diseases like Alzheimer's and Parkinson's disease are known, a major gap in our understanding relates to the precise pathways by which these proteins induce neuronal dysfunction - particularly initiating mechanisms - and how/where the various proteins operate in a given pathologic cascade. The Roy lab employs cellular models that capture key pathologic features of these diseases - for example synaptic dysfunction - to unravel mechanistic aspects of neurodegeneration. It is hoped that an accurate understanding of the pathobiology would lead to refined therapeutic targets.

Modeling Hematologic Disease with Induced Pluripotent Stem Cells

Eirini P Papapetrou, MD, PhD
Assistant Professor
Division of Hematology
University of Washington

Wednesday, February 6, 2013 - 4:30 PM
Health Sciences Center, Rm. T-739

Faculty Sponsor: Chuck Murry, MD, PhD

Why Attend?
The conversion of somatic cells into induced pluripotent stem cells (iPSCs) opened a new frontier for disease modeling and regenerative medicine. Eirini Papapetrou's research focuses on studying the cellular, molecular and genetic basis of hematologic diseases and on developing new approaches for cell and gene therapy using iPSC-based models. This talk will highlight how iPSCs can provide a novel platform for the safer genetic modification of human cells for gene therapy applications - with genetic correction of beta-thalassemia as a proof-of-principle - and for studying the pathogenesis and genetics of hematologic diseases - focusing on myelodysplastic syndromes.

WNT1 Mutations in Families with Moderately Severe and Progressive Recessive Osteogenesis Imperfecta

Shawna Pyott, PhD
Clinical Cytogenetics and Molecular Genetics Fellow
Departments of Pathology and Medical Genetics
University of Washington School of Medicine

Wednesday, January 30, 2013 - 4:30 PM
Health Sciences Center, Rm. T-739

Faculty Sponsor: Christine Disteche, PhD

Why Attend?
Shawna Pyott is a Postdoctoral Fellow in the Department of Pathology who studies osteogenesis imperfecta (OI), a rare disorder characterized by fragile bones and an increased risk for fracture. Mutations in COL1A1 and COL1A2 result in dominant forms of OI and account for 95% of individuals with OI. Recessive forms of OI account for the remainder and in several affected families, the causative gene has yet to be identified. Shawna Pyott will present her discovery of a new recessive OI gene, WNT1, that she identified as the mutated gene in four families with moderately severe and progressive OI. She will discuss the implications of her findings in relation to the known interactions of WNT1 and other proteins such as the co-receptor low-density lipoprotein receptor-related protein 5 (LRP5), which has been implicated in bone anomalies. These findings should lead to a better understanding of the role of WNT1 in bone development, stabilization, and structure, and may provide another OI subset in which targeted treatment could be effective.

Implementing Next-Generation Sequencing for Cancer Diagnostics

Colin C. Pritchard MD, PhD
Assistant Professor and Associate Director, Genetics and Solid Tumors Laboratory
Department of Laboratory Medicine
University of Washington School of Medicine

Wednesday, January 23, 2013 - 4:30 PM
Health Sciences Center, Rm. T-739

Faculty Sponsor: Marshall Horwitz, MD, PhD

Why Attend?
Newer "next-generation" DNA sequencing methods allow simultaneous assessment of mutations in many genes at once. This technology is especially promising for cancer diagnostics, both for germline sequencing for hereditary cancer risk, and for tumor-based sequencing for precision cancer therapy. Since 2011, the UWMC Genetics Lab has offered clinical assays for cancer diagnostics using next-generation sequencing technology. This presentation will review considerations related to clinical implementation of next-generation sequencing, and will cover the ColoSeq, BROCA, and UW-OncoPlex gene panels currently in clinical use for cancer patients and their families at UW and SCCA.

Novel Markers Predictive of Prostate Cancer Treatment Failure: The Limits of Morphology, and the Future of Prostate Cancer Molecular Diagnostics

Antoni Papanicolau-Sengos, MD
General Surgical Pathology Fellow
Department of Pathology
University of Washington School of Medicine

Wednesday, January 16, 2013 - 4:30 PM
Health Sciences Center, Room T-739

Faculty Sponsor: Larry True, MD

Why Attend?
Prostate carcinoma is the most common non-cutaneous cancer in men. Despite its frequency, only a small fraction of these carcinomas causes death. The challenge of choosing who to treat is tremendous. Currently, a good clinician and a good histopathologist are all that a patient with prostate cancer can ask for. Morphology is still the standard of care for diagnosis and prognosis. Recently, certain histological findings have emerged as biomarkers of neoadjuvant cytotoxic chemotherapy failure. However, morphology has its limits. One can think of morphologic findings as “macro� events that likely reflect only a component of a tumor’s behavior. With the development of new techniques of sequencing a new frontier has emerged, and with it the possibility that we can further subcategorize prostate cancer for more accurate prognosis and selection of patients for targeted therapy. In this presentation I will discuss recent efforts using histologic findings that suggest failure of neoadjuvant cytotoxic chemotherapy. In addition, I will provide you an update about recent molecular findings in prostate carcinoma, their promise and implications for diagnosis and treatment.

Molecular Diagnostics in Breast Pathology: Hot Topics & Current Trends

Kathi Adamson, MD and Nicole Andeen, MD
Breast Pathology Fellows
Laboratory Medicine
University of Washington

Wednesday, December 12, 2012 - 4:30 PM
Health Sciences Center, Rm. T-739

Faculty Sponsor: Kim Allison, MD

Why Attend?
Breast cancer is the most common cancer in women--come learn something about it!

You like molecular diagnostics? We do, too! We use these techniques everyday to help patients--join us and find out more.

Thinking about a career in assay development? Come learn about the current predictive/prognostic assays in breast pathology, issues with them and assay development.

The UWMC Breast Pathology service has lots of research projects and opportunities for collaboration. Come learn about what we are up to!

Role of Syndecan-1 During Influenza Infection

Peter Chen, MD
Assistant Professor, Center for Lung Biology
Division of Pulmonary and Critical Care Medicine
Uinversity of Washington

Wednesday, December 5, 2012 - 4:30 PM
Health Sciences Center, Rm. T-739

Faculty Sponsor: Bill Mahoney, PhD

Why Attend?
Influenza is a highly contagious respiratory illness that infects up to 50 million people in the United States yearly. We have been studying how the host responds to influenza infection and have found that syndecan-1, a proteoglycan expressed by the lung epithelium, limits the lung injury after influenza infection. This presentation will review the clinicopathologic findings of influenza infection and explore mechanisms by which syndecan-1 limits the morbidity and mortality after infection.

Engineering Microvasculature for the Study of Thrombosis and Thrombopoiesis

Ying Zheng, PhD
Research Assistant Professor
Department of Bioengineering
Uinversity of Washington

Wednesday, November 28, 2012 - 4:30 PM
Health Sciences Center, Rm. T-739

Faculty Sponsor: Mike Laflamme, MD, PhD

Why Attend?
Microvasculature support metabolic activity and define microenvironmental conditions within tissues in both health and disease. Recapitulation of functional microvascular structures in vitro could provide a platform for the study of complex spatial and temporal progression of tissue scale biology, including thrombosis and thrombopoiesis. We have recently engineered a living microvessel network in three dimensional tissue scaffolds and demonstrated their biofunctionality in vitro. This presentation will highlight two expanded work: one to decode the initial events of thrombosis under inflammation, and the other to recapitulate the process of platelet generation and define the functional components in the bone marrow niche. The success of the microvascular networks in recapitulating these phenomena points to the broad potential of this platform for the study of cardiovascular biology and pathophysiology.

Pathology and Pathogenesis of Neonatal Hemochromatosis

Lisa Pate, MD
Pediatric Fellow
Seattle Children's Hospital
University of Washington School of Medicine

Wednesday, November 14, 2012 - 4:30 PM
Health Sciences Center, Room T-739

Faculty Sponsor: Raj Kapur, MD

Why Attend?
Neonatal hemochromatosis (NH) is a rare, severe, and often fatal disease characterized by hepatic necrosis and iron deposition in certain extrahepatic tissues. NH is the most common cause of neonatal liver failure and the most frequent reason for liver transplantation in the first 3 months of life. It also causes late 2nd and 3rd-trimester fetal loss. Recurrence risk in future pregnancies is as high as 80%. NH does not share any of the gene mutations known to cause hereditary familial hemochromatosis. While NH has historically been thought to result from an inborn error of iron metabolism, recent evidence demonstrates that most NH cases result from a gestational alloimmune process, which activates the fetal complement cascade to cause hepatocyte injury. Extrahepatic iron deposition is probably secondary, in part due to deficiency of hepatocyte-derived factors, which regulate iron export from other tissues. Using recent cases from Seattle Children’s Hospital, Dr. Pate will provide an overview of the pathology of NH, including its clinical presentation, differential diagnosis, and histopathologic features, as well as a brief review of maternal-fetal alloimmunity, placental iron transport, and iron storage.

Sorting Through Ovarian Serous Tumors: Insights Into Classification and Pathogenesis

Christina Isacson, MD
Pathologist, CellNetix Pathology & Laboratories
Clinical Instructor, Department of Obstetrics and Gynecology
University of Washington Medical Center

Wednesday, November 7, 2012 - 4:30 PM
Health Sciences Center, Room T-739

Faculty Sponsor: Tom Motnine, MD, PhD

Why Attend?
Dr. Isacson is a gynecologic pathologist with a passion for teaching and women’s health issues. Her research interests include HPV-related disease, the molecular pathogenesis of female genital tract cancers and diagnostic immunohistochemistry. Dr. Isacson has served on the Editorial Board of the International Journal of Gynecological Pathology and currently is Section Editor for Archives of Pathology and Laboratory Medicine. She has a long standing relationship with the United States & Canadian Academy of Pathology where she has been on the Education Committee, served as Short Course Coordinator and was appointed to Council in 2011. She is also co-author of the widely used “An Illustrated Manual for the Dissection of Surgical Pathology Specimens�. This presentation will discuss hot topics in serous ovarian tumors with respect to disease classification and molecular pathways.

Mitochondrial Superoxide Production in the Heart

Wang Wang, MD, PhD
Assistant Professor
Anesthesiology and Pain Medicine
University of Washington School of Medicine

Wednesday, October 31, 2012 - 4:30 PM
Health Sciences Center, Room T-739

Faculty Sponsor: Bill Mahoney, PhD

Why Attend?
Free radicals play multi-functional roles in cell signaling and are also culprits of oxidative stress related disease, including cardiovascular disease. In the heart, superoxide produced through mitochondrial respiration is the major and primary source of free radicals. In this presentation, we will discuss how mitochondria produce superoxide under normal conditions and in oxidative stress related cardiovascular diseases. We will specifically introduce a newly developed superoxide indicator and the characterization of a transient bursting superoxide generating event discovered in individual mitochondria of living cardiac myocyte and in the beating heart. We will also discuss the mechanisms underlying this bursting mitochondrial superoxide production and its significance in cardiovascular diseases such as ischemia reperfusion injury and heart failure.

How Does a Cell Change Its Shape? (Insights from the Glomerular Podocyte)

Sheeram Alkilesh, MD, PhD
Renal Pathology Fellow
UW Medicine Pathology
University of Washington

Wednesday, October 24, 2012 - 4:30 PM
Health Sciences Center, Rm. T-739

Faculty Sponsor: Charlie Alpers, MD

Why Attend?
Cells come in a variety of shapes and sizes and can change their shape in pathologic situations. Cell shape is a manifestation of a carefully regulated actin filament based cytoskeleton. In this talk, I will propose that in the kidney, the glomerular podocyte is an excellent cell to study the effects of actin cytoskeletal regulation in vivo. The podocyte has a delicate dendritic morphology that is essential for proper kidney function. Changes in the shape of the podocyte are associated with spillage of serum proteins into the urine and kidney disease. I will discuss our current understanding of the mechanisms and consequences of podocyte shape change. These studies outline a framework to understand how different cell types may change their shape – and I will extend findings from the kidney to another system – melanoma metastasis. For the general pathologist/pathologist-in-training, this talk will provide a conceptual framework to appreciate the molecular basis of the diverse cell shapes we encounter daily under the microscope.

Nonalcoholic Fatty Liver Disease (NAFLD) and Hepatocellular Carcinoma: Two Growing Epidemics in a Fertile Liver

Matthew Yeh, MD, PhD
Associate Professor
UW Medicine Pathology
University of Washington

Wednesday, October 17, 2012 - 4:30 PM
Health Sciences Center, Rm. T-739

Faculty Sponsor: Paul Swanson, MD

Why Attend?
Matthew Yeh's research focuses on the investigation of nonalcoholic fatty liver disease (NAFLD) and liver cancer. NAFLD has emerged as an epidemic in the Western world and in other regions as the hepatic manifestation of metabolic syndrome, which is also a growing epidemic. There is a broad spectrum of its histopathology, ranging from steatosis to nonalcoholic steatohepatitis (NASH), with risk for progressive fibrosis that may lead to cirrhosis and hepatocellular carcinoma. For pathologists and pathology trainees, this talk is an update of the pathology of NAFLD, including its differential diagnosis and diagnostic pitfalls, its pathology in various non-traditional settings, and clinical correlation. Hepatocellular carcinoma, the most common primary liver cancer, has steadily increased in Europe and North America, and is currently the cancer with the fastest growing mortality rates in the United States. For researchers, this talk also explores the potential link between these two growing epidemics.

A Reappraisal of the Amyloid Hypothesis

Zak Hoffer, MD, PhD
Neuropathology Fellow
UW Medicine Pathology

Wednesday, October 3, 2012 - 4:30 PM
Health Sciences Center, Room T-739

Faculty Sponsor: Josh Sonnen, MD

Why Attend?
Despite decades of laboratory and clinical research, Alzheimer disease continues to affect millions of people. Central to the current understanding of Alzheimer disease is the "amyloid hypothesis", which posits that biochemical and cellular cascades lead to an overproduction of beta amyloid cleavage products that form neuritic plaques, and plaque burden is somehow linked to the development of cognitive deficits. However, in recent clinical studies, therapeutically decreasing plaque burden does not reverse or arrest the cognitive decline of Alzheimer disease. These disappointing results are prompting some researchers to reevaluate the central tenet of the amyloid hypothesis.

For the general pathologist and resident pathologist in training, this seminar will review the classic gross and microscopic neuropathologic features of Alzheimer disease, and discuss evidence for the amyloid hypothesis. For the neuropathologist, this seminar will review recent clinical data that expose flaws in the amyloid hypothesis, and will generate a discussion of new directions in Alzheimer research in light of the reappraisal.

Dr. Hoffer is an active duty pathologist. He completed training in anatomic and clinical pathology at Madigan Army Medical Center. Dr. Hoffer is interested in understanding how traumatic brain injury contributes to the development of neurodegenerative disorders like Alzheimer disease.

Bioengineering for Cardiac Repair

Nenad Bursac, PhD
Associate Professor
Biomedical Engineering
Duke University

Wednesday, June 13, 2012 - 4:30 PM
Health Sciences Center, Rm. K-069

Faculty Sponsor: Mike Laflamme, M.D., Ph.D.

Why Attend?
Nenad Bursac's research is aimed at use of cell, tissue, and genetic engineering methodologies and electrophysiological and biomechanical studies to advance fields of somatic and stem cell based therapies for cardiac and skeletal muscle disease. This work has involved: 1) combining DT-MRI and cell micropatternining techniques to create novel 2- and 3-dimensional cardiac cell cultures that replicate micro- and macrostructure of native myocardium, 2) development of specialized co-culture assays to study structural and functional interactions between cardiomyocytes and nonmyocytes, 3) a novel mesoscopic hydrogel molding technique for fabrication of large, aligned, and highly functional skeletal and cardiac muscle tissues derived from stem cells, and 4) generation of novel biosynthetic excitable cells and tissues for basic studies of ion channel function and use in somatic cell therapies for excitable tissue disease.

Mutation Rate as a Therapeutic Target in Cancer

Eddie Fox, Ph.D.
Post-Doc, Loeb Lab
UW Medicine Pathology
University of Washington

Wednesday, May 30, 2012 - 4:30 PM
Health Sciences Center, Rm. K-069

Faculty Sponsor: Larry Loeb, M.D., Ph.D.

Why Attend?
Mutations are a hallmark of cancer, with tens to hundreds of thousands of mutations present in every tumor genome. It has been proposed that these mutations arise from an increased rate of mutagenesis during tumor progression and provide a source of phenotypic variation, including resistance to chemotherapy. Dr. Fox has demonstrated that sequential selection of cancer cells for novel phenotypes, not related to mutagenesis, results in enhanced mutation rates. Thus, the evolution of cancer-related phenotypes itself favors the emergence of mutator lineages. To our knowledge, this this the first real-time demonstration of spontaneous acquisition of a mutator phenotype in a human tumor model. High levels of mutations in tumors, however, could be the Achilles’ heel for killing tumor cells based on targeting enhanced mutagenesis.

Nucleic Acid Detection in Host Defense and Autoimmunity

Dan Stetson, Ph.D.
Assistant Professor
UW Medicine Immunology
University of Washington

Wednesday, May 23, 2012 - 4:30 PM
Health Sciences Center, Rm. K-069

Faculty Sponsor: Kelly Smith, M.D., Ph.D.

Why Attend?
Research in the Stetson lab focuses on mechanisms by which cells detect and respond to viral infection. All of our cells have nucleic acid sensors that are essential for activating antiviral immunity. These sensors must be able to distinguish foreign nucleic acids from the abundance of self RNA and self DNA that is present in every cell. In particular, we discovered an innate immune response to intracellular DNA called the Interferon Stimulatory DNA (ISD) pathway, and we have been working to understand the sensors, signaling mechanisms, and relevance of this pathway for antiviral immunity. We found that aberrant activation of the ISD pathway by reverse transcribed DNA of endogenous retroelements causes a number of human autoimmune diseases, including Aicardi-Goutieres Syndrome. Dr. Stetson's presentation will describe recent efforts to characterize the sensors of the ISD pathway, its negative regulators, and its DNA virus-encoded antagonists.

Detection of Ultra-rare Mutations by Next Generation Sequencing

Michael Schmitt, MD, PhD
Post-Doc, Loeb Lab
UW Medicine Pathology
University of Washington

Wednesday, May 16, 2012 - 4:30 PM
Health Sciences Center, Room K-069

Faculty Sponsor: Larry Loeb, MD, PhD

Why Attend?
Next Generation DNA sequencing promises to revolutionize clinical medicine and basic research. However, while this technology can generate hundreds of billions of nucleotides of DNA sequence in a single experiment, the error rate of approximately 1% results in hundreds of millions of sequencing mistakes. These scattered errors can be tolerated in some applications but become extremely problematic when "deep sequencing" genetically heterogeneous mixtures, such as tumors or mixed microbial populations. To overcome limitations in sequencing accuracy, we have developed an alternative to standard sequencing approaches that allows for detection of rare mutations with unprecedented sensitivity.

The Molecular Regulation of Stem Cell Quiescence

CANCELLED: Thomas Rando, M.D., Ph.D.
Professor, Department of Neurology and Neurological Sciences
Director, Glenn Laboratories for the Biology of Aging
Stanford University Medical Center

Wednesday, May 9, 2012 - 4:30 PM
Health Sciences Center, Rm. K-069

Faculty Sponsor: Matt Kaeberlein, Ph.D.

Dr. Rando's seminar originally scheduled for Wednesday, May 9 has been cancelled due to clinical service obligations. We will reschedule Dr. Rando's visit in the next few months.

Context-dependent Responses to Hypoxia in C. Elegans

Dana Miller, PhD
Assistant
Department of Biochemistry
University of Washington

Wednesday, May 9, 2012 - 4:30 PM
Health Sciences Center, Room K-069

Faculty Sponsor: Matt Kaeberlein, PhD

Why Attend?
Oxygen is essential for all metazoans, with only one known exception. Inappropriate or inadequate responses to decreased oxygen availability (hypoxia) are hallmark features of traumatic injury and stroke, and contribute to many diseases that lead to significant human morbidity and mortality. Though there is a critical need to understand normal and pathological responses to hypoxia, few genetically tractable models have been developed that allow for unbiased investigation of hypoxia-responsive pathways. We have developed methods to investigate physiological strategies of adaptation to hypoxia in C. elegans, allowing simultaneous control of genotype and cellular environment in a living animal. Our studies reveal that the response to hypoxia depends greatly on the physiological context. We are working to understand the mechanistic basis of the context-dependent effects on hypoxia. This work will provide an important foundation to develop therapeutic strategies to protect cells and organisms from hypoxia.

Function of Nod-like Receptors in Intestinal Immunity

Gabriel Nunez, M.D.
Paul de Kruif Endowed Professor
Department of Pathology
University of Michigan Medical School

Wednesday, May 2, 2012 - 4:30 PM
Health Sciences Center, Rm. K-069

Faculty Sponsor: Kelly Smith, M.D., Ph.D.

Why Attend?
The Nunez laboratory is interested in mechanisms regulating innate immunity, the pathogenesis of inflammatory disease and the interaction of the microbiota with the host. Specifically, the research focuses on mechanistic studies to understand the role of pattern recognition receptors (PRRs) and in particular Nod-like receptors (NLRs) in the immune response against microbial pathogens and endogenous damage signals. Several NLR proteins including NOD2 and NLRP3 are mutated in patients with inflammatory diseases, Crohn's disease and autoinflammatory syndromes, respectively. However, the function of NLRs in host defense and the mechanisms by which NLR mutant proteins lead to disease remain unclear. Dr. Nuñez's presentation will present and discuss ongoing studies that attempt to understand the role of NLRs in host defense aqainst bacterial pathogens and inflammatory disease in the intestine.

Homing Endoncleases for Gene Targeting

Stefan Pellanz, PhD
Post-Doctoral Fellow
Monnat Lab
UW Medicine Pathology

Wednesday, April 25, 2012 - 4:30 PM
Health Sciences Center, K-069

Faculty Sponsor: Ray Monnat, MD

Why Attend?
Homing endonucleases are rare cutting endonucleases typically encoded in introns or inteins. Their ability to maintain high site specificity of cleavage while tolerating limited target site sequence divergence, together with tight coupling of DNA binding and cleavage, have made HEs attractive reagents for genome engineering. Recent development of HEs with altered specificities has demonstrated their value for targeted gene modifications. Our research focusses on the alteration of these enzymes in order to shift their specificity towards novel, therapeutically interesting target sites and the characterization of these engineered HE variants in living cells.

RIG-I Like Receptors in Infection, Immunity and Therapy

Michael Gale, Ph.D.
Professor, UW Medicine Immunology
Adjunct Professor, UW Medicine Global Health
University of Washington

Wednesday, April 18, 2012 - 4:30 PM
Health Sciences Center, Rm. K-069

Faculty Sponsor: Kelly Smith, M.D., Ph.D.

Why Attend?
Michael Gale, Jr., PhD, is the Director of the National Institutes of Health (NIH)-funded Center for the Study of Immune Mechanisms of Virus Control at the University of Washington, School of Medicine where his research program is focused on understanding the virus-host interactions that regulate innate immunity against RNA viruses. Dr. Gale is also the Director of a Center for the Study of Hepatitis C Virus Infection and Immunity, part of a national network of Hepatitis C Cooperative Research Centers funded by the NIH. In addition, his laboratory is also a component of the Pacific Northwest Regional Center of Excellence in Biodefense and Emerging Infectious Diseases, where he leads a research program to define therapeutic targets to control pathogenic flavivirus infection. Dr. Gale teaches virology, immunology, infectious disease biology, and public health to medical students and graduate students, and is a member of the editorial board of several biomedical research journals. He is currently a member of the Virology-B study section of the NIH.

CANCELLED Molecular Classification of Breast Cancer: Where Are We and Where Are We Going?

CANCELLED: Stuart Schnitt, M.D,
Professor, Department of Pathology
Director, Anatomic Pathology, Beth Israel Deaconess Medical Center
Harvard Medical School

Wednesday, April 11, 2012 - 5:00 PM
Health Sciences Center, Rm. K-069

Faculty Sponsor: Residents/Mara Rendi, M.D.

This seminar has been cancelled due to a death in the speaker's family. It will be rescheduled in the next few months.

Why Attend?
Stuart Schnitt is the Director of the Division of Anatomic Pathology at Beth Israel Deaconess Medical Center in Boston and a Professor of Pathology at Harvard Medical School. He is also a Past President of the United States and Canadian Academy of Pathology. Dr. Schnitt is an internationally recognized expert in breast pathology, author of a highly acclaimed breast pathology textbook (Biopsy Interpretation of the Breast), and an editor of the 4th Edition of the WHO Classification of Tumours of the Breast. His research interests in the area of breast diseases is broad and in recent years has focused increasingly on the integration of traditional pathology with newer molecular techniques to refine breast tumor classification, assessment of breast cancer risk in women with benign breast disease, and risk of local recurrence in women with invasive breast cancer and DCIS treated with breast conserving therapy.

The Influence of Alternative pre-mRNA Processing in Gene Expression and Disease

Klemens Hertel, Ph.D.
Professor
Department of Microbiology and Molecular Genetics
Univeristy of California, Irvine

Wednesday, March 21, 2012 - 4:30 PM
Health Sciences Center, Rm. K-069

Faculty Sponsor: Pathology Graduate Students

Why Attend?
Research in the Hertel laboratory focuses on elucidating the regulation of alternative splicing with the ultimate goal to faithfully predict pre-mRNA processing changes in disease models. With the realization that most diseases are molecularly heterogeneous, novel high throughput technologies have been employed to identify gene expression markers that could be used for early detection and improved prognosis. However, gene expression levels alone cannot fully explain a cellular phenotype or gene functions without considering alternative pre-mRNA processing. Dr. Hertel’s presentation will discuss the prevalence, mechanisms, and potential implications of alternative pre-mRNA processing in maintaining cellular homeostasis.

CAP-Transformation of a Specialty

Paul Valenstein, MD, FCAP
President, Pathology and Laboratory Management Associates, P.C.
Member, CAP Council on Accreditation
Vice Chair, CAP Council on Scientific Affairs

Wednesday, March 14, 2012 - 4:30 PM
Health Sciences Center, K-069

Faculty Sponsor: Ben Hoch, MD

Why Attend?
Changes in the organization of care, the availability of funding, and technology advancements have the potential to create a "perfect storm" for the pathology specialty. How will individual practitioners and pathology practices adapt? Dr. Valenstein will discuss some of the challenges and opportunities facing the specialty, and provide insights into steps that can be taken to accelerate adaption in a rapidly evolving market.

Synergistic Regulation of cAMP-mediated Functions by Multiple PDEs

Joe Beavo, Ph.D.
Professor
UW Medicine Pharmacology
University of Washington

Wednesday, March 7, 2012 - 4:30 PM
Health Sciences Center, Rm. K-069

Faculty Sponsor: Jean Campbell, Ph.D.

Why Attend?
Many different physiological and pathophysiological processes are controlled by cAMP- and cGMP-dependent regulatory processes. The amplitude and duration of these cyclic nucleotide signals are in turn controlled by both their rates of synthesis by adenylyl and guanylyl cyclases and their rates of degradation by cyclic nucleotide phosphodiesterases (PDEs). Multiple isozymes of both cyclases and phosphodiesterases have been identified and shown to be important for the ability of the cell to adapt to its environment. Moreover, it also has been amply demonstrated that a particularly good way to pharmacologically manipulate these cyclic nucleotide signals is to modulate the activity of the PDEs that control their degradation. This lecture will address current ideas about how pharmacological regulation of these enzymes has been approached in the past with the goal of obtaining efficacy without side effects and will also suggest likely new and better approaches for the future. Experimental examples to illustrate this approach will be largely from regulation of steroidogenesis by cAMP but the lessons learned are likely to be widely applicable.

A Systems Approach to Dissecting Immunity

Alan Aderem, Ph.D.
President and Director, Seattle BioMed
Affiliate Professor of Immunology and Medicine, University of Washington
Seattle Biomedical Research Institute

Wednesday, February 29, 2012 - 4:30 PM
Health Sciences Center, Rm. K-069

Faculty Sponsor: Kelly Smith, M.D., Ph.D.

Why Attend?
Alan Aderem, co-founder of the Institute for Systems Biology, is a pioneer in the field of systems biology and is an internationally recognized immunologist and cell biologist. His research focuses on the innate immune system – how it recognizes and formulates responses to infectious agents, and how it instructs the adaptive immune system to provide long-lived immunity to the pathogen. The Aderem laboratory also applies the tools of systems biology to the study of diseases that significantly impact global health with an emphasis on rational vaccine design. He has recently taken over the helm of Seattle BioMed.

Association of Hyaluronan Metabolic Biomarkers and Inflammation with Aggressiveness in Prostate Cancer

Stephen Schmechel, MD, PhD
Assistant Professor and Director of Cytopathology
Department of Laboratory Medicine
University of Minnesota

Wednesday, February 15, 2012 - 4:30 PM
Health Sciences Center, Room K-069

Faculty Sponsor: Tom Montine, MD, PhD

Why Attend?
Steve Schmechel is Assistant Professor and Director of Cytopathology in the Department of Laboratory Medicine at the University of Minnesota (UMN), and founding Director of the UMN Academic Health Center's Biological Materials Procurement Network (BioNet), a central biobank, research histopathology, and digital imaging resource. BioNet supports research by 71 UMN principal investigators and additional studies at other universities and companies in the medical device, biotechnology, and pharmaceutical industries. The Schmechel laboratory utilizes BioNet functions to identify and validate gene products and other metabolic biomarkers of aggressive biologic behavior of prostate cancer. Recent results support a model that a mechanism of aggressive prostate cancer biology is the synthesis of hyaluronan (by HAS2), accumulation of hyaluronan, degradation (presumably) of some hyaluronan (by Hyal1) into hyaluronan fragments*, and upregulation of signaling via the Rhamm pathway that promotes a response including CD45-positive) inflammation.

PKA Mutations Regulate Energy Homeostasis in Mice

Stan McKnight, Ph.D.
Professor
UW Medicine Pharmacology
University of Washington

Wednesday, February 8, 2012 - 4:30 PM
Health Sciences Center, Rm. K-069

Faculty Sponsor: Jean Campbell, Ph.D.

Why Attend?
We count on neurons in the hypothalamus to integrate signals from the rest of our body and balance energy intake with our energy expenditure. For most of us, this means we are not constantly gaining or losing weight. The system works reasonably well in humans and in mice until faced with highly palatable, calorie dense foods and an environment where exercise is discouraged by elevators, cars, and in the case of mice, small cages. The result in the US population is that ~60% of us are overweight and ~30% are classified as obese with all of the adverse health effects associated with obesity. Our lab is studying mice with genetically engineered defects in the cAMP/PKA system that protect animals from diet-induced obesity and also have stimulatory effects on voluntary exercise. Our hypothesis is that these changes in signal transduction pathways in leptin-responsive neuronal circuits have produced mice that are hyper-sensitive to leptin, suppressing the normal tendency to store more fat in adipose tissue.

Electrophysiology and Calcium Handling of Human Embryonic Stem Cell-Derived Cardiomyocytes

Wei-Zhong Zhu
Post-Doc, Laflamme Lab
UW Medicine Pathology
University of Washington

Wednesday, February 1, 2012 - 4:30 PM
Health Sciences Center, Rm. K-069

Faculty Sponsor: Mike Laflamme, M.D., Ph.D.

Why Attend?
Human embryonic stem cell-derived cardiomyocytes (hESC-CMs) have tremendous promise as a cell source for regenerative medicine. To optimize host-graft electromechanical integration and minimize the risk of arrhythmias following transplantation, however, hESC-CMs must have the appropriate electrophysiological properties and mechanisms of excitation-contraction coupling. Toward that end, I will present our recent work on two topics related to the electrical behavior of hESC-CMs in vitro. First, I will describe advances in the derivation of specialized cardiac subtypes (e.g., pacemaker cells) from hESCs, using genetic selection and pharmacological manipulation of neuregulin-ErbB signaling. Second, I will review our current understanding of the mechanisms of excitation-contraction coupling and calcium handling in hESC-CMs, which seem to be surprisingly adult-like given their relatively immature structure and mechanical properties.

The Challenge of Finding a Clinically Useful Tissue-Based Prostate Cancer Biomarker: A Personal Perspective

Larry True, M.D.
Professor
UW Medicine Pathology
University of Washington

Wednesday, January 11, 2012 - 4:30 PM
Health Sciences Center, Rm. K-069

Faculty Sponsor: Larry Loeb, M.D., Ph.D.

Why Attend?
Based on my multi-year investigation of tissue-based cancer biomarkers, I will discuss some of the challenges that we all face in identifying prognostic and predictive markers, and proposed solutions. Although I'll focus on markers specific to the prostate, the challenges are common to all cancers. Issues to be discussed include sampling, tumor heterogeneity, observer-variability, prognostic and predictive transcriptomes and proteomes, and quantitative tissue assays.

Deciphering the Mitochondrial Contribution to Intracellular Signaling

Brian Hawkins, Ph.D.
Assistant Professor, UW Medicine Anesthesiology and Pain Medicine
Researcher, Mitochondria and Metabolism Center
University of Washington

Wednesday, December 14, 2011 - 4:30 PM
Health Sciences Center, Room K-069

Faculty Sponsor: Bill Mahoney, Ph.D.

Why Attend?
Mitochondria are ubiquitous organelles that are the primary source of energy for most eukaryotic organisms. Aside from ATP generation, mitochondria contribute to intracellular signaling pathways during growth, differentiation, proliferation, and even cell death. Perturbations in mitochondrial function consequently influence a number of conditions including cardiovascular disease, cancer, and neurodegeneration. Due to this almost universal impact on multiple cellular processes and diseases, defining the precise molecular mechanism(s) by which mitochondria decode and transmit cellular metabolic cues into downstream signaling has proven difficult. Our laboratory specializes in delineating how mitochondria direct intracellular signaling by focusing on the delicate relationship between calcium and redox homeostasis. This seminar will highlight our current understanding of mitochondrial-initiated signaling cascades via calcium and reactive oxygen species (ROS) and will introduce a novel means in which mitochondria initiate intracellular signaling through physiologic mitochondrial permeability transition. We anticipate that the identification of unique mitochondrial signaling molecules and pathways will serve as attractive therapeutic targets aimed at combating human disease.

Molecular Logic of Neocortical Projection Neuron Development, Degeneration, and Regeneration

Jeffrey Macklis, M.D.
Professor, Stem Cell and Regenerative Biology
Program Head, Neuroscience / Nervous System Diseases Harvard Stem Cell Institute
Harvard University

Wednesday, December 7, 2011 - 4:30 PM
UW Health Sciences Center, Rm. K-069

Faculty Sponsor: Chuck Murry, M.D., Ph.D.

Why Attend?
Jeffrey D. Macklis' laboratory is directed toward both 1) understanding molecular controls over neuron sub-type specification and development in the cerebral cortex, and 2) applying developmental controls toward brain and spinal cord repair - specifically, the cellular repair of complex cerebral cortex and cortical output circuitry (in particular, cortico-spinal motor neuron (CSMN) circuitry that degenerates in ALS and other "upper motor neuron" degenerative diseases, and whose injury is centrally involved in loss of motor function in spinal cord injury). The Macklis lab focuses on neocortical projection neuron development and sub-type specification; neural progenitor / "stem cell" biology; induction of adult neurogenesis (the birth of new neurons from within); and directed neuronal differentiation and development of connectivity via molecular manipulation of neural progenitors within murine neocortex. The same biology informs understanding of neuronal subtype specificity of involvement in human neurodegenerative and developmental diseases, in particular ALS / motor neuron disease, PLS, HSPs, Huntington's disease, autism spectrum disorders, and Rett Syndrome.

Proteolytic Pathways in Innate Immunity

William Parks, Ph.D.
Professor
Director, Center for Lung Biology
UW Medicine

Wednesday, November 30, 2011 - 4:30 PM
UW Health Sciences Center, Rm. K-069

Faculty Sponsor: Mike Laflamme, M.D., Ph.D.

Why Attend?
Innate immunity involves the action of resident cells and leukocytes to maintain and restore healthy tissues challenged by injury and infection. As for most biological processes, the extent, pattern, and duration of inflammation are controlled by a balance between positive and negative factors. Matrix metalloproteinases (MMP) have emerged as important effector enzymes that act on diverse proteins to promote or moderate various immune processes. This presentation will highlight two MMPs-MMP7 and MMP10-that control distinct and somewhat opposing immune processes in response to injury and infection. In acute injury, matrilysin (MMP7) controls the transepithelial advancement and activation of neutrophils by shedding the ectodomain of syndecan-1, a transmembrane heparan sulfate proteoglycan. Similar to MMP7, stromelysin-2 (MMP10) is not expressed in resting tissues; however, in response acute or chronic insults, this proteinase is induced by infiltrated macrophages. In models of acute and chronic inflammation, Mmp10–/– mice have an exaggerated inflammatory response, indicating that the enzyme functions normally to repress inflammation. However, whereas Mmp10–/– mice are susceptible to lethality from acute insults, they are protected against tissue damage associated with prolonged inflammation. Data from both models indicate that MMP10 impact macrophage functions by promoting differentiation into immunosuppressive M2 (alternatively activated) cells. Together, these findings demonstrate both pro- and anti-inflammatory functions of distinct MMPs.

Bone Marrow Derived Cells in Cardiac Repair: From Mouse to Man

April Stempien-Otero, M.D.
Associate Professor, UW Medicine Cardiology
Craig and Julie Tall Endowed Professor in Heart Failure Research
University of Washington

Wednesday, November 16, 2011 - 4:30 PM
Health Sciences Center, Room K-069

Faculty Sponsor: Bill Mahoney, Ph.D.

Why Attend?
Bone marrow-derived cells are critical to myocardial repair contributing directly to cardiac components such as endothelium and fibroblasts and providing paracrine factors that direct neovascularization and collagen production by resident cells. Current data support a model in which bone marrow monocyte-derived macrophages are at the crux of these repair processes in acute injury. Thus, macrophages are an attractive target for cell-based therapies to improve myocardial repair and prevent progression to heart failure. Our interest is in the role of a specific macrophage protease–urokinase plasminogen activator–in directing macrophage phenotype in the heart in mouse models. Moreover, we have initiated human studies of bone marrow cell therapy to the heart to elucidate the role of macrophages and bone marrow derived stem cells in end-stage human heart disease.

Cell Signaling in Space and Time

John D. Scott, Ph.D.
Edwin G. Krebs-Speights Professor of Cell Signaling and Cancer Biology
Department of Pharmacology
University of Washington School of Medicine

Wednesday, November 9, 2011 - 4:30 PM
Health Sciences Center, Room K-069

Faculty Sponsor: Jean Campbell, Ph.D.

Why Attend?
Dr. John Scott is a Howard Hughes Investigator and the Edwin G. Krebs-Speights Professor of Cell Signaling and Cancer Biology with the Department of Pharmacology, University of Washington. Dr. Scott is a fellow of the Royal Society, London, the Royal Society of Edinburgh. He's the author of over 200 scientific articles in peer-reviewed journals and books. He is interested in the specificity of signal transduction events that are controlled by anchoring proteins, which facilitate rapid signal transduction by optimally positioning protein kinases and phosphatases in the vicinity of their activating signals and close to their substrates. His research program focuses on defining the intracellular communication networks that promote specificity in signal transduction events. Dr. Scott's lab has identified a family of A-kinase-anchoring proteins (AKAPs) that target the cAMP-dependent protein kinase (PKA) and other signaling enzymes to specific subcellular sites. AKAPs influence the regulation of physiological processes by bringing enzymes close to their appropriate effectors and substrates at precisely the right moment. Dr. Scott and his lab have made significant progress on establishing the AKAP model, the functional consequences of PKA anchoring, and the bigger role of AKAP signaling networks in the coordinate regulation of cellular signaling.

Diverse Functions of SKN-1/Nrf Proteins in Stress Defenses and Aging

Keith Blackwell, M.D., Ph.D.
Co-Head, Islet Cell and Regenerative Biology, Joslin Diabetes Center
ofessor of Genetics, Harvard Medical School
Harvard Medical School

Wednesday, November 2, 2011 - 4:30 PM
UW Health Sciences Center, Rm. K-069

Faculty Sponsor: Matt Kaeberlein, Ph.D.

Why Attend?
Most chronic diseases can be considered to be aging-related, in that they manifest themselves primarily in older individuals. In model organisms both lifespan and healthspan can be increased dramatically by dietary restriction or manipulation of certain metabolic or stress defense pathways, holding promise that an understanding of these mechanisms may ultimately be of great benefit for human health. We study aging in the nematode C. elegans, an advantageous organism for pathway discovery. In the seminar I will describe how a protein that protects against oxidative stress (the SKN-1/Nrf transcription factor) also defends against various other metabolic and proteotoxic stresses. I will also describe how SKN-1/Nrf plays a critical role in an opposing relationship between growth and nutrient signals on one hand, and stress defense mechanisms on the other. This relationship may be of critical importance in dietary restriction, and other growth/nutrient-related mechanisms that influence aging.

What Leads to Age-Related Changes in the Lenses of Our Eyes? Some Factors Related to Increasing Lens Opacity Leading to Cataract

Norm Wolf, D.V.M., Ph.D.
Professor
UW Medicine Pathology
University of Washington

Wednesday, October 26, 2011 - 4:30 PM
UW Heatlh Sciences Center, Rm. K-069

Faculty Sponsor: Kelly Smith, M.D., Ph.D.

Why Attend
My laboratory studies age-related changes in the lens in several species. I will present our studies on changes in mouse, rat, dog, monkey, human and bovine lenses. We also study the long known but, we believe, never satisfactorily explained replication condition of two adjacent regions of the lens surface cells- the non-replicating central zone, and the continuously replicating germinative zone next to it. I also will briefly touch on the role of the Sirt1 gene as it directly or indirectly affects age-related lens opacity.

Fixing the Furnace: A Mitochondrial Targeted Therapy for Energy-deficient Diseases

Hazel Szeto, M.D., Ph.D.
Professor
Department of Pharmacology
Weill Cornell Medical College

Wednesday, October 19, 2011 - 4:30 PM
Health Sciences Center, Room K-069

Faculty Sponsor: Peter Rabinovitch, M.D., Ph.D.

Why Attend?
Dr. Szeto is co-discoverer of a class of mitochondrially targeted peptide drugs that have increasingly wide potential application. Originally thought to behave a simple antioxidant, it is now apparent that the tetrapeptide agent SS-31 directly enhances mitochondrial respiration under diverse conditions of mitochondrial energetic stress. It has been found to have benefits, for example, in attenuating ischemia reperfusion injury to the kidney, heart and brain, and to improve heart and muscle function under oxidative challenge. SS-31 is now in phase II clinical trial for prevention of cardiac injury following acute myocardial infarction.

Distinctive Features of Liver Immunology

Ian N. Crispe, M.D., Ph.D.
Member, Seattle BioMed
Affiliate Professor, UW Medicine Immunology
Seattle BioMed

Wednesday, October 12, 2011 - 4:30 PM
UW Health Sciences Center, Rm. K-069

Faculty Sponsor: Jean Campbell, Ph.D.

Why Attend?
The liver is the site of common infectious diseases (HAV, HBV, HCV), essential in the development of malaria parasites, and subject to metabolic diseases with an immuno-inflammatory component. There is increasing recognition that immune responses have distinctive local features, and in the liver these are shaped by constitutive exposure to trace levels of bacterial products from the intestinal microbiota. In the presentation, some distinctive features of liver immunology will be discussed. Specifically, we will address: the distinctive lymphocyte populations in the liver; the presentation of hepatocellular antigens to T cells; recruitment of T cells to the liver; and the nature of hepatic immune failure. Experimental models to be discussed include primary human liver leukocytes, AAV gene therapy vectors, and genetically-altered malaria parasites.

Role of Sphingosine 1-Phosphate in Muscle Regeneration: Potential Pharmacotherapy for Muscular Dystrophy

Morayma Reyes, M.D., Ph.D.
Assistant Professor
UW Medicine Pathology
University of Washington

Wednesday, October 5, 2011 - 4:30 PM
UW Health Sciences Center, Rm. K-069

Faculty Sponsor: Jean Campbell, Ph.D.

Why Attend?
Presently, there is no effective treatment for the lethal muscle wasting disease Duchenne Muscular Dystrophy. In collaboration with Dr. Hannele Ruohola-Baker, through an unbiased suppression screen of the dystrophic phenotype in Drosophila, we found suppressors that upregulate the levels of sphingosine 1 phosphate (S1P) and thereby ameliorate the dystrophic phenotype in the flies. Previously, S1P has been implicated in satellite cell proliferation and myoblast differentiation in vitro. These essential roles for S1P in skeletal muscle enabled us to hypothesize that S1P mechanisms are conserved in mammals. In extending the S1P studies to the mdx mouse, we found that localized elevation of S1P via direct injection into muscle led to an increase in muscle satellite cell proliferation, newly regenerated fibers as well as fiber size. Additionally, we found that the systemic administration of that 2-acetyl-4(5)-tetrahydroxybutyl imidazole (THI), an S1P lyase inhibitor that strongly suppressed dystrophic muscle wasting in Drosophila, led to a significant amelioration of known hallmarks of DMD pathology, fibrosis and fat deposition and dramatic increase in muscle fiber size in mdx mice. Similar results were also observed in the dysferlinopathy mouse model, AJ/SCID mice with direct administration of S1P. This increase in muscle fiber size can be attributed to anabolic pathways as indicated by increased levels of phosphorylated ribosomal S6. Thus, THI holds promise as a new pharmacotherapy to treat muscular dystrophy. I will present a general discussion of S1P metabolism and its role in cellular processes with emphasis on the skeletal muscle. I will also discuss the pathology of muscular dystrophy and current challenges in finding therapies to treat this lethal, devastating disease.

Dynamic Recruitment of MicroRNAs to mRNA Targets in the Regenerating Liver

Linda Greenbaum, M.D.
Associate Professor of Cancer Biology
Associate Professor of Medicine, Division of Gastroenterology and Hepatology
Thomas Jefferson Medical College

Wednesday, June 8, 2011 - 4:30 PM
Health Sciences Center, Rm. K-069

Faculty Sponsor: Jean Campbell, Ph.D.

Why Attend?
The regenerative capacity of the liver is essential for recovery in response to hepatocyte loss due to acute or chronic viral, metabolic or toxic liver injury. Although microRNAs have been implicated for regulation of proliferation in a variety of tissues including patients with hepatocellular carcinoma and other liver diseases, the mRNAs targeted by specific microRNAs and their function during hepatocyte proliferation is not well understood. Obstacles that have limited identification of important mRNA:miRNA functional relationships have included the identification of a small number of differentially expressed miRNAs in the regenerating liver and limited prediction power of current miRNA prediction programs. We applied the HITS-CLIP assay (high-throughput sequencing of RNA isolated by crosslinking immunoprecipitation; Licatolosi, Nature 2008) to the partial hepatectomy model, an established model of liver regeneration. We have identified a large number of mRNAs that are bound by miRNAs in the regenerating liver, thus expanding the functional importance of microRNAs for regulation of liver regeneration. In addition, this assay has allowed us to identified miRNA binding sites in the coding region, 5'UTR in addition to 3'UTR regions of mRNAs. We are currently validating selected miRNA targets target and will use gain and loss-of-function approaches to elucidate the function of these miRNAs during the regenerative response. We anticipate that these studies will advance the current understanding of how miRNAs regulate hepatocyte proliferation in physiologic and pathophysiological states including cirrhosis and hepatocellular carcinoma.

Axon Degeneration: A Neglected Therapeutic Target in Parkinson's Disease

Robert Burke, M.D.
Professor, Neuroology and Pathology
Director, Udall Parkinson's Disease Research Center
Columbia Unversity

Wednesday, June 1, 2011 - 4:30 PM
Health Sciences Center, Rm. K-069

Faculty Sponsor: Jing Zhang, MD, PhD

9th Annual Alvord Lecture in Neuropathology
A special lecture in memory of the life and scientific legacy of Ellsworth C. Alvord, Jr., M.D. (1923-2010), Professor and Chief, UWMC Neuropathology, 1960-2002.

Calcium Currents, Mitochondrial Stress and Parkinson's Disease

Dalton Surmeier, Ph.D.
Professor and Chair, Ph.D.
Department Physiology
Feinberg School of Medicine, Northwestern University

Wednesday, May 25, 2011 - 4:30 PM
Health Sciences Center, Rm. K-069

Faculty Sponsor: Tom Montine, M.D., Ph.D.

Why Attend?
Dr. D. James Surmeier is the Nathan Smith Davis Professor and Chair of the Department of Physiology at the Feinberg School of Medicine at Northwestern University and Director of the Morris K. Udall Research Center of Research Excellence for Parkinson's Disease at Northwestern University. Dr. Surmeier received his Ph.D. in Physiology and Biophysics from the University of Washington in 1983. He trained with leaders in the field of neurophysiology, including Dr. Arnold Towe, Dr. William Willis, and Dr. Stephen Kitai. In 1998, he moved to the Department of Physiology at Northwestern University and assumed his current position in 2001. Dr. Surmeier's research program focuses on the basal ganglia – neural structures controlling movement and intimately involved in the pathophysiology of Parkinson's disease. He has authored over 150 peer-reviewed publications in journals such as Science, Nature, Neuron, Nature Neuroscience and the Journal of Neuroscience. He has served in several advisory capacities to the National Institutes of Health, including chairing study sections for the National Institute of Neurological Disorders and Stroke (NINDS) and acting as a Councilor for NIAAA. He also serves on the scientific advisory boards of several private foundations and serves on a number of editorial boards, including Molecular and Cellular Neuroscience, Neuron and Current Opinion in Neurobiology. He was elected as a Fellow of the American Association for the Advancement of Science and has received many other scientific awards including the NARSAD Established Investigator award, the Riker Award, the Picower Foundation Award, and the Jacob Javits Neuroscience Investigator Award.

A Genetic Mechanism of the Evolutionary Theory of Aging:

Rong Yuan, Ph.D.
Scientific Manager, Jackson Aging Center
Research Scientist, Jackson Laboratory
Jackson Laboratory, Bar Harbor, Maine

Wednesday, May 18, 2011 - 4:30 PM
Health Sciences Center, K-069

Faculty Sponsor: Matt Kaeberlein, Ph.D.

Why Attend?
The objective of my research, guided by the evolutionary theory of aging, is to discover biomarkers of aging and healthspan that can be measured at an early age. Then I use mouse genetics and bioinformatics methods to identify genes that regulate these markers and investigate the effects of these genes on aging and healthspan. My overall goal is to define new ways of delaying aging and extending healthspan.

The CSF-1 Receptor and its Ligands in Development, Cancer and Inflammatory Disease

E. Richard Stanley, Ph.D.
Renee and Robert A. Belfer Professor of Developmental Biology
Professor, Department of Developmental and Molecular Biology
Albert Einstein College of Medicine

Wednesday, May 4, 2011 - 4:30 PM
Health Sciences Center, Rm. K-069

Faculty Sponsor: Elaine Raines, M.S.

Why Attend
Colony stimulating factor-1 (CSF-1), or M-CSF, controls macrophage and osteoclast production and function. These cells, via trophic and scavenger actions, play critical roles in development. CSF-1, via its receptor (CSF-1R), also regulates development of other cell types, including Langerhans cells and Paneth cells, plays autocrine and paracrine roles in neoplasia and is an important regulatory cytokine in many chronic inflammatory diseases. The identification of a second CSF-1R ligand, IL-34, coupled with studies of CSF-1 receptor signal transduction, offer new approaches to our understanding of the regulation by the CSF-1R and its role in these diseases.

Breast Cancer Testing: From Arbitrary to Evidence Based

Kim Allison, M.D.
Assistant Professor, UW Medicine Pathology
Director, UW Medicine Pathology Breast Service
University of Washington

Wednesday, April 20, 2011 - 4:30 PM
Health Sciences Center, Room K-069

Faculty Sponsor: Tom Montine, M.D., Ph.D.

Why Attend?
Tissue-based testing of tumors in pathology has evolved from serving a diagnostic purpose to providing key information about the likelihood a particular neoplasm will respond to a specific therapeutic agent. Because these test results have such a large impact on treatment decisions, there has been a recent focus on standardizing how these tests are performed, interpreted, reported and validated. Dr. Allison will discuss current issues in setting the standards for testing in breast cancer including sentinel lymph node analysis, HER2 testing, hormone receptor testing and RT-PCR based tests, with a focus of where current standards may need to be reevaluated.

Using Human Pluripotent Stem Cells to Study Hepatic Disease and Development

Stephen Duncan, Ph.D.
Professor, Human and Molecular Genetics
Director, Regenerative Medicine and Stem Cell Biology
Medical College of Wisconsin

Wednesday, April 13, 2011 - 4:30 PM
Health Sciences Center, Room K-069

Faculty Sponsor: Graduate Program Students

Why Attend?
Dr Duncan is the Markus Professor of Human and Molecular Genetics and Director of the Regenerative Medicine Program at the Medical College of Wisconsin. He has authored over 70 articles in scientific journals and books. His research focuses on the use of mice and stem cells to understand the contribution of transcription factors during embryonic development and function of the liver, pancreas, and heart. Traditionally his lab has relied on the use of mouse models including knockout mice and mouse embryonic stem cells. During this time the laboratory has garnered a substantial understanding of the basic molecular pathways controlling hepatic function and development. While the mouse has been a valuable model, the Duncan lab has introduced the use of induced human and mouse pluripotent stem cells as well as human embryonic stem cells because of the belief that they could offer a new and robust experimental model. Members of the Duncan lab have shown that they can control differentiation of human pluripotent stem cells into hepatocytes with high efficiency, to the extent that >95% of cells in the culture dish express characteristic markers of differentiated hepatocytes. In addition they have developed technologies to control differentiation of hepatocytes into both cardiac and pancreatic-like cells. Such approaches have raised the possibility of using stem cell–derived cells for the study of the fundamental molecular mechanisms underlying hepatic, cardiac and pancreatic disease and development.

A Journey in Translational Research: From Molecular Mechanisms in Chemical Carcinogenesis to a Phase I Clinical Trial on Adverse Drug Interactions

David Eaton, Ph.D.
Associate Vice Provost, Office of Research
Professor, Env. and Occ. Health Sciences
University of Washington

Wednesday, April 6, 2011 - 4:30 PM
Health Sciences Center, Room K-069

Faculty Sponsor: Tom Montine, M.D., Ph.D.

Why Attend?
Dr. Eaton received his Ph.D. in pharmacology from the University of Kansas Medical Center (KUMC) in 1978, then joined the UW School of Public Health in 1979, and has been here ever since. He is Professor of Environmental and Occupational Health Sciences, with adjunct appointments in Public Health Genetics and Medicinal Chemistry, and serves as founding Director of the Center for Ecogenetics and Environmental Health. He served as Associate Dean for Research in the School of Public Health from 2000-2005, and as Associate Vice Provost for Research from 2005-2010. He is currently Interim Vice Provost for Research, at the UW. He has published over 150 scientific articles and book chapters in the field of toxicology. Dr. Eaton is an Elected Fellow of the American Association for the Advancement of Science and the Academy of Toxicological Sciences, and a Lifetime National Associate of the National Academies of Sciences. This talk will describe an adventure to discover the molecular basis for a remarkable species difference in susceptibility to the potent liver carcinogen, aflatoxin B1, and how unexpected discoveries along the way led to a phase I clinical trial to prevent adverse drug interactions in HIV/AIDS patients being treated for TB.

Innate Immunity Genetics & Susceptibility to Tuberculosis

Thomas Hawn, M.D., Ph.D.
Associate Professor
UW Medicine Allergy and Infectious Diseases
University of Washington

Wednesday, March 30, 2011 - 4:30 PM
Health Sciences Center, Room K-069

Faculty Sponsor: Kelly Smith, M.D., Ph.D.

Why Attend?
Why do humans respond differently to infections? How does genetic variation of human innate immunity genes regulate inflammation? To address these questions, Dr. Hawn studies the role of Toll-like Receptors (TLRs) and other genes in coordinating the innate immune response of macrophages to bacterial infection with an emphasis on tuberculosis. He uses a combination of molecular, cellular, and human genetic techniques to pursue an overall research goal of understanding the genetic basis and molecular mechanisms of human susceptibility to infectious diseases.

Role of PDGF-C in the Genesis of the Hepatic Tumor Microenvironment

Jean Campbell, Ph.D.
Assistant Professor
UW Medicine Pathology
University of Washington

Wednesday, March 16, 2011 - 4:30 PM
Health Sciences Center, Room K-069

Faculty Sponsor: Matthew Yeh, M.D., Ph.D.

Why Attend?
Hepatocellular carcinoma (HCC) most commonly arises in the setting of chronic inflammation and cirrhosis, supporting the hypothesis that an abnormal microenvironment contributes to disease progression. Yet understanding the complex cellular interactions in the liver that contribute to the evolution of the tumor microenvironment, and ultimately to tumorigenesis, has been challenging due to a lack of animal models that recapitulate the disease progression observed in humans. During this presentation I will describe a unique mouse model of hepatocellular carcinogenesis that mimics the step-wise progression from fibrosis to cirrhosis, and finally to HCC. We are exploiting this model to understand the role of non-parenchymal cells in regulating fibrogenesis and neoangiogenesis, and to define the contribution of these cells to the tumor microenvironment. My talk will highlight data demonstrating the merits of using this pre-clinical model to evaluate therapeutic strategies that target the hepatic tumor microenvironment by blocking the processes that contribute to its development, including fibrosis and angiogenesis.

Using Network Modeling to Predict Wnt Pathway Dysregulation

Hamid Bolouri, Ph.D.
Research Member
Division of Human Biology
Fred Hutchinson Cancer Research Center

Wednesday, March 9, 2011 - 4:30 PM
Health Sciences Center, Rm. K-069

Faculty Sponsor: Kelly Smith, M.D., Ph.D.

Why Attend?
Inter-individual variations, and (nonlinear) gene-gene and gene-environment interactions complicate the analysis of healthy and dysregulated cellular processes. Network models offer integrated views of cellular pathways and can be used to highlight hidden features of large-scale datasets, and to arrive at insights and testable hypotheses. In this talk, I will present a case study in which we used network modeling to re-analyze published data and arrived at new insights and hypotheses. Our methodology is novel in its approach, straight-forward in usage, and general in its applicability to other cellular pathways and processes. For more information please visit Dr. Bolouri's website: http://labs.fhcrc.org/bolouri/

The Role of the Hypoxic Stress Pathway in Worm Aging

Scott F. Leiser, Ph.D.
Post-Doctoral Fellow
Kaeberlein Lab
UW Medicine Pathology

Wednesday, March 2, 2011 - 4:30 PM
Health Sciences Center, Rm. K-069

Faculty Sponsor: Matt Kaeberlein, Ph.D.

Why Attend?
The aging process is involved in the development of many of the most common human pathologies. By using model organisms to find conserved aging pathways, we are searching for ways to slow human aging and prevent many diseases. Using the nematode, C. elegans, our lab and others have recently implicated a role for the highly-conserved hypoxia pathway in aging. Initial papers suggest that the hypoxia inducible factor, HIF-1, can act as both a positive and negative regulator of aging in worms. This seminar will discuss how HIF-1 can affect lifespan and healthspan in worms and how this work may translate to future human research.

Molecular Classification of Breast Cancer: What Have We Learned?

David Dabbs, M.D.
Chief of Pathology
Magee Women's Hospital
University of Pittsburgh Medical Center

Wednesday, February 16, 2011 - 4:30 PM
Health Sciences Center, Room K-069

Faculty Sponsor: Dr. Mara Rendi

Why Attend?
The molecular classification of breast cancer has ushered in a new perspective on breast carcinomas. This classification offers a framework that is useful to clinicians and pathologists, and has spawned a host of rival molecular tests that are touted as predictors of patient outcomes to therapy. Select aspects of these molecular tests will be discussed in concert with traditional pathologic analysis of breast carcinomas

CANCELLED due illness. Rescheduled seminar TBA.

Alan Adereem, Ph.D.
Co-Founder, Institute for Systems Biology
Affiliate Professor, UW Medicine Immunology
Institute for Systems Biology

Wednesday, February 9, 2011 - 4:30 PM
Health Sciences Center, Room K-069

Faculty Sponsor: Kelly Smith, M.D., Ph.D.

Why Attend?
Macrophages and dendritic cells represent one of the cornerstones of the innate immune system. They detect infectious organisms and then orchestrate an appropriate host response to them. In order to precisely define the nature of the threat the immune cell needs to read the molecular bar code that is displayed on the specific pathogen. The molecular bar codes have been referred to as PAMPS and they are recognized by pattern recognition receptors (PRR). The Toll-like receptors (TLRs) and the Nod-like receptors (NLRs) are prototypic PRRs that detect extracellular PAMPS and intracellular PAMPS respectively. Since infectious agents carry many different PAMPS the information must be integrated in order to define the specific pathogen and enable the host to formulate an appropriate response. We use the tools of systems biology to identify the molecular networks that lead to this decision-making. Biological results and technological developments will be discussed.

Applying Oligonucleotide Aptamers to Diagnostic Pathology and Laboratory Medicine

Geoffrey Baird, M.D., Ph.D.
Assistant Professor, UW Laboratory Medicine
Adjunct Assistant Professor, UW Medicine Pathology
UW Medicine

Wednesday, February 2, 2011 - 4:30 PM
Health Sciences Center, Room K-069

Faculty Sponsor: Tom Montine, M.D., Ph.D.

Why Attend?
Oligonucleotide aptamers are short strands of DNA or RNA that specifically bind other chemical species, much in the same way as monoclonal antibodies. Despite being discovered nearly 20 years ago, none of the hundreds of published applications of aptamers have penetrated into current anatomic or clinical pathology practice, and only very few are utilized in the research setting. This seminar will cover the reasons why this has happened and how the trend is now reversing, focusing on the potential benefits of incorporating aptamers into both clinical and research pathology. Specifically, the seminar will cover work in our laboratory and others describing how one may use aptamers for tissue and fluid proteomics, biomarker discovery, and histochemistry.

Patient-Specific Mathematical Neuro-Oncology: A Paradigm Shift in Glioma Treatment

Kristin Swanson, Ph.D.
Associate Research Professor
UW Medicine Pathology
University of Washington

Wednesday, January 26, 2011 - 4:30 PM
Health Sciences Center, K-069

Faculty Sponsor: Kelly Smith, M.D., Ph.D.

Why Attend?
Gliomas are complex heterogeneous tumors with a spectrum of behaviors with an overall dismal prognosis. The relative low incidence and the wide variability of this disease across (and within) patients is a challenge to routine clinical studies to determine optimal treatment strategies. This heterogeneity suggests a patient-specific quantification of disease kinetics and treatment response is essential to improving outcomes for these patients. This seminar will discuss the role of the burgeoning field of Mathematical NeuroOncology specifically focusing on the practical application of patient-specific mathematical modeling approaches in providing predictive insight into tumor growth kinetics and response to therapy in individual patients.

The Cooperation of Epigenetic and Genetic Alterations in Gastrointestinal Cancer

William Grady, M.D.
Associate Professor
UW Medicine
University of Washington

Wednesday, January 19, 2011 - 4:30 PM
Health Sciences Center, Room K-069

Faculty Sponsor: Matthew Yeh, M.D., Ph.D.

Dr. Grady will discuss the role of genetic alterations and epigenetic alterations that occur in colon cancer on the behavior of the cancer cells. In particular, an understanding of signal network deregulation and gene cooperation will be gained from attending this lecture.

This seminar was originally scheduled for December 15, 2010.

T Cell Therapy of Cancer

Cassian Yee, M.D.
Professor, UW Medicine Oncology
Member, Clinical Research Division, FHCRC
University of Washington

Wednesday, January 12, 2011 - 4:30 PM
Health Sciences Center, Room K-069

Faculty Sponsor: Kim Allison, M.D.

Why Attend?
A Renaissance in immunotherapy or another passing fad? My NIH reviewers want to know. Find out what I told them and where the field is headed.

Mouse Model of Leigh Syndrome: Identifying Critical Brain Regions Involved

Richard Palmiter, Ph.D.
Professor
UW Medicine Biochemistry
University of Washington

Wednesday, January 5, 2011 - 4:30 PM
Health Sciences Center, Room K-069

Faculty Sponsor: Tom Montine, M.D., Ph.D.

Why Attend?
Leigh syndrome is a necrotizing encephalopathy caused by mitochondrial dysfunction due to mutations in either mitochondrial or nuclear genes involved in electron transport. We have created a mouse with a mutation in Ndufs4, one of the 45 subunits of complex 1, the recapitulates virtually all of the symptoms of Leigh syndrome. We have shown that the disease is caused by mitochondrial dysfunction in the central nervous system and that it results in progressive gliosis, and eventually neuronal loss, in the olfactory bulb, vestibular nucleus and cerebellum. The knockout mice have breathing defects that may be responsible for their demise by about 50 days after birth. Selective inactivation of Ndufs4 in the vestibular nucleus results in premature death, whereas selective restoration of Ndufs4 in the vestibular nucleus prolongs life.

A Systems-Pathology Approach in Transplantation

Michael Mengel, M.D.
Associate Professor
Laboratory Medicine and Pathology
University of Alberta Hospital

Wednesday, December 8, 2010 - 4:30 PM
Health Sciences Center, Room K-069

Faculty Sponsor: Charles Alpers, M.D.

Why Attend?
After studying medicine at the Semmelweiss University in Budapest, Hungary, Dr. Mengel did his residency in the Department of Pathology at Hannover Medical School, Germany. While there he became specialized in pathology and subsequently transplantation and nephropathology. He was head of the transplant pathology service with responsibility for diagnostics and research based on transplant biopsies at the transplant centre in Hannover. In collaboration with the Department of Nephrology, one of the largest protocol biopsy programs after renal transplantation was established at the transplant centre in Hannover. In December 2006 he came to the University of Alberta in Edmonton, Canada and joined the Alberta Transplant Applied Genomics Centre (Director Philip F. Halloran) where he had the opportunity to apply modern molecular microarray techniques together with sophisticated bioinformatics tools to well-documented clinical material from large biopsy series. Currently he is a Lead Investigator at the Alberta Transplant Applied Genomics Centre and his major research focus is the molecular based refinement of the histopathological assessment of organ transplant biopsies. In November 2008 he joined the faculty as an Associate Professor in the Division of Anatomical Pathology where he assumed the role of the Section Head of Transplantation Pathology.

Microchimerism and Cancer

V.K. Gadi
Assistant Professor
UW Medicine
University of Washington

Wednesday, December 1, 2010 - 4:30 PM
Health Sciences Center, Room K-069

Faculty Sponsor: Kim Allison, M.D.

Why Attend?
A prior history of pregnancy is generally a protective factor against malignancy. How this protection is mediated is presently not completely understood. Dr. Gadi's work involves the study of fetal microchimerism, small numbers of stably persistent cells in a woman originally derived from her fetus. In this seminar, the data supporting a protective role of fetal microchimerism against breast cancer will be discussed.

Companion Diagnostics; The Pathologist as the Prescribing Physician

David Rimm, M.D., Ph.D.
Professor
Department of Pathology
Yale University School of Medicine

Wednesday, November 17, 2010 - 4:30 PM
Health Sciences Center, Room K-069

Faculty Sponsor: Larry True, M.D.

Why Attend?
Personalized medicine has put the pathologist in a key position with respect to patient care. Companion diagnostic tests are now required for therapeutic decisions that can save patients lives. So exactly how accurate those tests? This seminar will explore the accuracy of current companion diagnostic tests in breast cancer. You may be surprised to see data that suggests your treatment depends on where you send your tissue. Sources of error, including sampling, pre-analytic variables, and reagents will be shown. Then alternative methods of standardization using quantitative immunofluorescence (AQUA) will be illustrated. Finally some exploratory data for new companion diagnostics will be presented.

Discovery of 8-Hydroxyguanine (8-oxo-G); Involvement in Mutagenesis and Cancer

Susumu Nishimura
Visiting Scholar
Laboratory Animal Resource Center
University of Tsukuba, Japan

Wednesday, November 10, 2010 - 4:30 PM
Health Sciences Center, Room K-069

Faculty Sponsor: Larry Loeb, M.D., Ph.D.

Why Attend?
Damage to DNA by oxygen free radicals results from both endogenous metabolic processes and from exposure to environmental agents. In cells, it is estimated that as many as 20,000 nucleotides in DNA are altered per cell per day. Twenty-five years ago, Dr. Susumu Nishimura discovered that 8-hydroxydeoxyguanosine is the principal adduct resulting from oxygen mediated DNA damage. He then established methods to quantify its mutagenic potential and the association of this damage with cancer. He used knockout mice with mutations in DNA repair genes to demonstrate repair of 8- hydroxyguanine lesions in DNA. There is considerable evidence to indicate that 8- hydroxyguanine lesions are involved in human colon and lung cancers. His current studies are directed at reducing the formation of 8- hydroxyguanine lesions in DNA and reducing the frequency by which these lesions mis-code in order to prevent or delay the emergence of human cancers.

Nephrotic T Cells: From Immunological Synapses to the Genetics of FSGS

Andrey Shaw, M.D.
Professor
Department of Pathology & Immunology
Washington University School of Medicine

Wednesday, November 3, 2010 - 4:30 PM
Health Sciences Center, Room K-069

Faculty Sponsor: Jing Zhang, M.D., Ph.D.

Why Attend?
Our work on the immunological synapse led us unexpectedly to become interested in podocytes in the kidney. Our recent work has focused on the genetic causes of FSGS and how the role of NextGen sequencing may transform our understanding of this disease.

Quantifying Proteins by LC-MS/MS

Andy Hoofnagle, M.D., Ph.D.
Assistant Professor
UW Laboratory Medicine
University of Washington

Wednesday, October 27, 2010 - 4:30 PM
Health Sciences Center, Room K-069

Faculty Sponsor: Tom Montine, M.D., Ph.D.

Why Attend?
There have been significant advances in the quantification of proteins by liquid chromatography-tandem mass spectrometry. Targeted proteomics workflows have major advantages over traditional automated immunoassays in the clinical laboratory. In addition, they are more precise than shotgun proteomics approaches. Using standard isotope dilution methods, we have developed several assays that demonstrate the utility of targeted mass spectrometry for the quantification of proteins in human samples. We will discuss the development of these assays and their application to tumor marker detection in serum and to studying the mechanisms of lipoprotein metabolism.

Immunologic Targeting of Oncogenic Proteins in Breast Cancer

Nora Disis, M.D.
Professor
UW Medicine Oncology/Tumor Vaccine Group
University of Washington

Wednesday, October 20, 2010 - 4:30 PM
Health Sciences Center, Room K-069

Faculty Sponsor: Kim Allison, M.D.

Why Attend?
Human cancers are immunogenic. Immunogenic proteins expressed by tumors have been defined and, in the case of breast cancer, many antigens are proteins that are involved in initiating or maintaining the malignant transformation. The identification of tumor antigens has allowed the development of targeted approaches to immune based breast cancer prevention and treatment strategies. The use of genetically engineered mice provides a model system for investigating the mechanism of action of breast cancer vaccines and clinical trials of vaccines in patients with breast cancer have indicated what type of immune response is needed for tumor eradication.

Monocyte/Macrophage Reprogramming - Novel Mechanisms to Control Outcomes in Inflammatory Diseases

Jeremy Duffield, M.D., Ph.D.
Associate Professor
UW Medicine
University of Washington

Wednesday, October 13, 2010 - 4:30 PM
Health Sciences Center, Room K-069

Faculty Sponsor: Charles Alpers, M.D.

Why Attend?
Jeremy Duffield recently joined University of Washington as Associate Professor of Medicine. He graduated from Oxford University in England, UK (MD) and Edinburgh University, Scotland UK (PhD) and moved to the USA in 2003. He was appointed Assistant Prof of Medicine at Harvard Medical School in 2006, after postdoctoral training there. He is a member of the Nephrology division and directs the Laboratory of Inflammation Research at the South Lake Union Campus in the Stem Cell and Regenerative Medicine Institute focused on the role of innate immune response cells, monocytes, in injury and repair and on the role of pericytes in vascular remodeling and fibrosis. Dr. Duffield is a recipient of the Young Investigator Award from the British Renal Association (2001), the Gottschalk Award from the American Society of Nephrology (2006) and an ARRA Challenge Grant from the NIH (2009) and the NIDDK Early Career Investigator/Scholar Award (2010). He serves on a study section at the NIDDK and the Scientific Advisory Board of Promedior Inc. and Regulus Therapeutics. He practices Nephrology part time at the UW Medical Center with special interests in Systemic Lupus Erythematosis, Systemic Vasculitis and Pregnancy related kidney disorders.

In his 'spare' time he races bicycles, climbs mountains, skis, plays tennis, grows organic vegetables, looks after children (his own) and fixes things that are broken.

Renal Mitochondrial Dysfunction in a Mouse Model of Diabetic Nephropathy

Bardia Askari, Ph.D.
UW Medicine Pathology
University of Washington School of Medicine

Wednesday, October 6, 2010 - 4:30 PM
Health Sciences Center, Room K-069

Faculty Sponsor: Charles Alpers, M.D.

Why Attend?
Diabetic nephropathy is a major complication of diabetes mellitus, affecting approximately 20-40% of all people diagnosed with diabetes and has become the major cause of end stage renal disease. The risk is even higher in Native-American, African-American and Hispanic populations with type 2 diabetes. Current treatment of diabetic nephropathy includes strict dietary, glycemic and blood pressure control with the use of renin-angiotensin-aldosterone system blockers. However, even in the presence of appropriate pharmacotherapy, diabetes can lead to nephropathy and kidney failure. While progressive diabetic nephropathy is most likely the result of a combination of environmental and genetic influences, the exact mechanisms are not clearly delineated. The mouse strain BTBR with the ob/ob leptin deficiency mutation develops severe type 2 diabetes, hypercholesterolemia, elevated triglycerides, and insulin resistance. We have demonstrated that these mice rapidly develop renal lesions characteristic of both early and advanced human diabetic nephropathy with corresponding renal dysfunction along with changes in the expression in several regulators of mitochondrial biogenesis. We've also demonstrated an amelioration of the development of type 2 diabetes using a novel peroxisome proliferator activated receptor (PPAR) agonist. These observations can give us a clearer view of the pathophysiologic mechanisms underlying the development of diabetic kidney disease.

Regulation of Neointimal Hyperplasia by Sphingosine-1-phosphate in Mice

Guenter Daum, Ph.D.
Research Associate Professor
UW Medicine Surgery
University of Washington

Wednesday, June 30, 2010 - 4:30 PM
Health Sciences Center, Turner Auditorium, Rm. D-209

Faculty Sponsor: Chuck Murry, M.D., Ph.D.

Why Attend
Intimal hyperplasia is a severe complication of surgical interventions to restore blood flow. In various models of arterial injury, smooth muscle cell (SMC) proliferation correlates with loss of expression of contractile proteins including smooth muscle alpha actin (SMA). Sphingosine-1-phosphate (S1P) is a phospholipid produced by platelets and other cells in response to injury. In this lecture I will present genetic and biochemical data linking S1P, and its receptors, to the control of smooth muscle migration and proliferation during neointimal formation.

Speaker is a candidate for an adjunct faculty appointment with UW Medicine Pathology

Of Old Mice and Men: Lessons in Comparative Pathology from a Mouse Model of Healthy Aging

Piper M. Treuting, D.V.M., M.S., DACVP
Assistant Professor, UW Comparative Medicine
Chief of UW Comparative Pathology Services
University of Washington

Wednesday, June 9, 2010 - 4:30 PM
Health Sciences Center, K-069

Faculty Sponsor: Suzanne Dintzis, M.D., Ph.D.

Why Attend,
Biomedical research institutions worldwide are literally over run with mice. The majority of extramural NIH funded grants use animals and the overwhelming majority of the research animals are mice. Mouse model development and validation is often performed by a team of scientists including comparative pathologists who understand how research may be impacted by mouse pathobiology such as the interplay of the mouse background strain with genetic manipulations, husbandry, age or commensal organisms. In this seminar, I will present the data generated by the end-of-life pathological analysis of old mice overexpressing mitochondrial-targeted catalase (mCAT) to highlight some of the unique features of mice and mouse-based research including species-specific anatomy and disease spectrum that make mice such useful, yet challenging, human disease models.

The Adventitia: A Novel Hedgehog Signaling Domain and Progenitor Cell Niche in the Vessel Wall

Mark Majesky, Ph.D.
Professor, UW Medicine Pediatrics
Seattle Children's Research Institute
University of Washington

Wednesday, June 2, 2010 - 4:30 PM
Health Sciences Center, K-069

Faculty Sponsor: Stephen M. Schwartz, M.D., Ph.D.

Why Attend
An adventitia surrounds most blood vessels where it functions as a dynamic compartment for cell trafficking into and out of the vessel wall. Adventitial cells regulate vascular growth, remodeling, angiogenesis and defense against infection. Recent studies report unexpected roles for the adventitia insofar as it provides a niche environment for resident vascular stem and progenitor cells. Since all organs contain blood vessels, adventitial stem cells may be important for morphogenesis, repair and disease involving many different tissues and cell types. The roles of sonic hedgehog signaling in vascular development and the origins and fates of vascular progenitor cells will be discussed.

Window of Opportunity: Artificial Cornea Development for Treatable Blindness Worldwide

Tueng Shen
Associate Professor
University of Washington Eye Institute

Wednesday, May 26, 2010 - 4:30 PM
Health Sciences Center, Room K-069

Faculty Sponsor: Chuck Murry

Why Attend
Treatable blindness, such as cataract and corneal blindness, are already a significant burden on global health and this burden is increasing. The majority of patients with treatable blindness live in the developing world. Common treatments used in developed countries are not viable options in the developing nations due to large discrepancy of health care infrastructure. The research in our laboratory aims to develop innovative solutions that can be applied for the developing world, leveraging cutting edge technology in material science, microelectronics and through collaborations while as the same time, addressing the cost and implementation constraints of the global market. The most recent results of artificial cornea development and drug delivery systems will be presented.

Pyroptosis: Coordinated Inflammatory Response

Brad Cookson
Professor
Laboratory Medicine & Microbiology
University of Washington

Wednesday, May 19, 2010 - 4:30 PM
Health Sciences Center, Room K-069

Faculty Sponsor: Chuck Murry

Why Attend
Eukaryotic cell death is an important and regulated host response, and one outcome is inflammation. We use microbial pathogens as biological probes to query the operation and function(s) of pyroptosis, a caspase-1-dependent pathway of programmed inflammatory cell death. The Greek roots pyro relates to fire or fever and ptosis (to-sis) denotes "a falling" or cell death. Pyroptosis results from the activation of a conserved effector pathway in response to diverse stimuli, with relevance to a variety of diseases in humans in which inflammation plays a central role.

Apoptosis and Autophagy: Neuropathology in the Balance

Kevin Roth, M.D., Ph.D.
Professor and Chair
Department of Pathology
University of Alabama at Birmingham

Wednesday, April 21, 2010 - 4:30 PM
Health Sciences Center, Room K-069

Faculty Sponsor: Dirk Keene

Why Attend?
Research in my laboratory is focused on the molecular regulation of neuronal cell death. Neuronal cell death occurs both during normal nervous system development and in a variety of neuropathological processes. The two major types of regulated cell death are apoptosis and autophagic cell death. While the processes controlling apoptotic cell death are fairly well characterized, the cellular and molecular regulation of autophagic cell death is poorly understood. We use a variety of in vivo and in vitro model systems to define the key molecules and cellular processes that regulate both apoptotic and autophagic cell death in neural stem cells, neurons and nervous system neoplasms. The long-term goals of my laboratory are to define the interactions between apoptotic and autophagic cell death pathways in the nervous system and to use this information to develop effective neuroprotective strategies to inhibit pathological neuron death and identify novel cell death-inducing compounds for the treatment of malignant glial neoplasms.

Microbe Hunting in the 21st Century

Ian Lipkin, M.D.
Professor
Departments of Epidemiology, Neurology and Pathology
Columbia University Medical Center

Wednesday, April 14, 2010 - 3:30 PM
Health Sciences Center, Turner Auditorium, Room D-209

Faculty Sponsor: Michael Linden

This is a special Path Presents/Grand Rounds hosted by the Departments of Pathology and Laboratory Medicine.

Please note time and location change.

Severe Gastrointestinal Motility Disorders: Understanding the Underlying Pathology of the Neuromuscular Apparatus of the Gut

Michael Schuffler
Professor
UW Medicine Gastroenterology
University of Washington

Wednesday, April 7, 2010 - 4:30 PM
Health Sciences Center, Room K-069

Faculty Sponsor: Melissa Upton

Why Attend
Gastrointestinal motility disorders are common and responsible for much pain and suffering. Until relatively recently, little was known about the pathology of these disorders. The experimental approach in humans has consisted mainly of physiologic studies to the exclusion of structure. Because of methodologic limitations and relative lack of interest in the morphology of the human muscularis propria and enteric nervous system, the pathology of these structures has received scant attention. My research focused on the pathology of the enteric nervous system and smooth muscles in patients with motility disorders. My lecture will provide an understanding of this pathology and will suggest an approach that conceivably, could be used in the general pathology department to diagnose these disorders.

Diagnosis and Management of Barrett's Esophagus and its Neoplastic Complications

Robert Odze, M.D., F.R.C.P.C
Professor, Harvard Medical School
Department of Pathology
Brigham and Women's Hospital

Wednesday, March 31, 2010 - 4:30 PM
Health Sciences Center, K-069

Faculty Sponsor: Melissa Upton, M.D.

Why Attend
Adenocarcinoma of the esophagus is rapidly rising in incidence in the Western world, and is caused by Barrett's esophagus. Cancer develops in Barrett's through a metaplasia-dysplasia-carcinoma sequence. There are controversies regarding establishing a diagnosis of Barrett's. The pathogenesis, pathology, natural history, and management of its neoplastic complications are also a subject of controversy. This lecture will focus on new insights, and the pathologic and molecular mechanisms involved, in the development of columnar metaplasia, dysplasia, and carcinoma of the esophagus. This lecture will provide guidelines for pathologists and clinicians who treat patients with this disorder.

Non-Cell Autonomous Neurodegeneration: A Tale of Two Glia

Gwenn Garden
Associate Professor
UW Medicine Neurology
University of Washington

Wednesday, March 24, 2010 - 4:30 PM
Health Sciences Center, Room K-069

Faculty Sponsor: Tom Montine

Why Attend
The extra-cellular environment is a critical contributor to the pathogenesis if neurodegenerative diseases. Our laboratory is studying the role of the neural environment in a number of specific neurological diseases including HIV Associated Neurocognitive Disorders (HAND), Alzheimer's disease (AD) and Spinocerebellar Ataxia Type 7 (SCA7). Our overarching hypothesis is that altered regulation of normal glial cell function contributes both actively and passively to eventual neurodegeneration in these diseases. We are evaluating the role of specific molecular regulators of the microglia inflammatory response in HAND and AD with the long term goal of identifying molecular pathways that could serve as therapeutic targets that could develop into disease modifying therapies. In SCA7, a disease caused by inheriting a CAG repeat expansion in the ataxin 7 gene, we have discovered an important role for a specialized cerebellar glial cell, the Bergmann glia. The SCA7 disease gene causes altered Bergmann glia functions that contribute to the eventual degeneration of cerebellar neurons and the neurological symptoms of SCA7.

Natural and Artificial Extra-visual Ocular Photoreception

Russ Van Gelder, M.D., Ph.D.
Professor and Chair
UW Medicine Ophthalmology
University of Washington

Wednesday, March 17, 2010 - 4:30 PM
Health Sciences Center, Room K-069

Faculty Sponsor: Chuck Murry

Why Attend
In the past ten years, we have come to the realization that the vertebrate eye serves as more than the organ of sight. Additional photoreceptor pathways exist in vertebrate eyes, controlling circadian rhythms, sleep, pupillary light responses, and likely seasonal behavior patterns. These pathways are mediated by novel photopigments including melanopsin and cryptochromes. Examples of recent work in chemically conferring photosensitivity on non-natively photoreceptive cells in the eye will also be discussed.

Microfluidics-assisted Display of Genomic DNA for Analysis of DNA Replication and Repair in Vivo

Julia Sidorova, Ph.D.
Acting Assistant Professor
UW Medicine Pathology
University of Washington

Wednesday, March 3, 2010 - 4:30 PM
Health Sciences Center, K-069

Faculty Sponsor: Ray Monnat

Why Attend?
DNA damage and enzymatic malfunction during DNA replication can be major sources of genomic instability. We focus on the functional analysis of DNA replication and repair under conditions of genotoxic stress as it unravels in living cells. Towards this end we have adapted a microfluidics-assisted approach to displaying individual molecules of genomic DNA on glass surfaces suitable for staining and microscopy. This technology allows us to measure DNA replication and repair in different genetic backgrounds and under different environmental stresses. We will discuss the novel insights we derived into the response of replication to blockage caused by nucleotide starvation, and the roles of the human RecQ helicases, WRN and BLM, in this process.

Mapping Gene Expression in the CNS: Tools and Data from the Allen Institute for Brain Science

Allan Jones, Ph.D.
Chief Scientific Officer
Allen Institute for Brain Science

Wednesday, February 24, 2010 - 4:30 PM
Health Sciences Center, Room K-069

Faculty Sponsor: Ray Monnat, M.D.

Why Attend?
The Allen Institute for Brain Science is a non-profit research organization dedicated to providing tools and data for the larger research community. Since 2003, the Allen Institute has created a suite of large-scale data efforts along with a web portal to view and analyze the data. These efforts include gene expression atlases of the developing and adult mouse brain and spinal cord, and developing and adult human and non-human primate gene expression studies. The presentation will cover an overview of the Allen Institute, its projects and infrastructure, a look at a few specific examples of gene expression in the mouse and human as they relate to genetic diversity, and introduce some of the new projects on the horizon for the Institute.

Common Disease - Multiple Rare Alleles: Understanding the Genetic Basis of Complex Human Traits

Mary-Claire King
Professor
Medicine & Genome Sciences
University of Washington

Wednesday, February 10, 2010 - 4:30 PM
Health Sciences Center, Room K-069

Faculty Sponsor: Chuck Murry

Why Attend?
Human disease is characterized by marked genetic heterogeneity, far greater than previously appreciated. Converging evidence for a wide range of common diseases indicates that heterogeneity is important at multiple levels of causation: (1) individually rare mutations collectively play a substantial role in causing complex illnesses; (2) the same gene may harbor many different rare severe mutations (hundreds or even thousands) in unrelated affected individuals; (3) the same mutation may have different effects in different individuals; and (4) mutations in different genes in the same or related pathways may all lead to the same disorder. This degree of allelic, locus, and phenotypic heterogeneity has important implications for gene discovery and for development of molecular treatments and their appropriate use by individual patients.

RNA-based Molecular Circuitry for Conditional Gene Regulation

Georg Seelig, Ph.D.
Assistant Professor
Electrical Engineering, Computer Science & Engineering
University of Washington

Wednesday, February 3, 2010 - 4:30 PM
Health Sciences Center, Room K-069

Faculty Sponsor: Ray Monnat

Why Attend?
In the first part of this talk I will review my recent work on DNA nanotechnology. Together with collaborators, I have advanced a general mechanism for implementing molecular computation using nucleic acids. Using DNA strand-displacement reactions as a molecular primitive we have been able to implement feed-forward digital logic circuits and, more recently, have proposed a method for implementing arbitrary chemical reaction kinetics in actual DNA-based chemistry. The circuit design principles that helped to make this circuitry robust and reliable will be useful to the construction of reliable circuitry for gene regulation control. In the second part of this talk I want to review work currently ongoing in my lab. We are interested in building nucleic acid-based sensors, logic gates and actuators that can detect cellular RNA inside living cells and, in response to varying expression patterns, can differentially and autonomously regulate gene expression. These synthetic regulatory elements are in part based on our in vitro DNA circuitry but also take advantage of existing RNA-based regulatory pathways, in particular the microRNA (miRNA) pathway and the RNA interference (RNAi) pathway.

Imaging Circuit Assembly in the Developing Retina

Rachel Wong
Professor
Department of Biological Structure
University of Washington

Wednesday, January 27, 2010 - 4:30 PM
Health Sciences Center, Room K-069

Faculty Sponsor: Suzy Dintzis

Why Attend?
Proper functioning of the nervous system requires the formation and maintenance of precise connectivity patterns between neurons. Our laboratory focuses on developmental mechanisms that regulate precision in circuit assembly of retinal neurons. Using live-cell imaging approaches to visualize retinal synaptogenesis under normal or perturbed developmental conditions, we have uncovered unexpected strategies by which neurons establish their mature connectivity patterns.

High Throughput Screening at the UW: RNA Interference and Small Molecule Screens

Carla Grandori and Tom Martins
Research Associate Professors
Quellos High Throughput Screening Core, ISCRM
UW Medicine Pharmacology

Wednesday, January 20, 2010 - 4:30 PM
Health Sciences Center, Room K-069

Faculty Sponsor: Ray Monnat

Why Attend?
High Throughput Screening (HTS) has revolutionized the way biomedical research can be conducted. Utilizing laboratory automation and robotics, HTS enables scientists to study complex biological systems and identify therapeutic drug candidates in reasonable timeframes that previously were improbable. The Quellos High Throughput Screening Core, located within the UW's Institute for Stem Cell and Regenerative Medicine at the UW School of Medicine campus in the South Lake Union area now provides HTS technology to both the Seattle academic community as well as its Biotech industry. This facility enables both genomic scale RNA interference screens as well as screening of large compound libraries for drug discoveries.

Further Information
Website: www.depts.washington.edu/uwhts/

Contact Info
General Core Facility Contact:
uwhts@uw.edu

For RNA Interference Screening
Carla Grandori; grandc@uw.edu
James Annis; annisj@uw.edu

For Chemical Screening
Tim Martins; tmartins@uw.edu

Functional Genetic Approaches in In Vitro Stem Cell Systems Using RNAi

Patrick Paddison, Ph.D.
Assistant Member
Human Biology Division
Fred Hutchinson Cancer Research Center

Wednesday, January 13, 2010 - 4:30 PM
Health Sciences Center, Room K-069

Faculty Sponsor: Ray Monnat

Why Attend?
While RNA interference (RNAi) first emerged as a peculiarity of nematodes, the molecular machinery that underlies RNAi is found in virtually every experimental eukaryotic system and has been co-opted in most to trigger gene silencing. RNAi has become a methodology of choice for knocking down gene expression in cultured mammalian cells has delivered new insights into a host of disease-related processes, including concrete information on potential drug targets. Its use has been expanded to in vivo applications in model rodent systems, including the ex vivo manipulation and transplantation of hematopoietic stem cells. Dr. Paddison's group focuses on applications of genome-scale RNAi libraries in embryonic, adult and cancer stem cell systems to reveal genes responsible for self-renewal, differentiation, and cancer homeostasis.

PET Imaging Tumor Phenotype in Sarcomas

Janet Eary, M.D.
Associate Professor
Department of Nuclear Medicine
University of Washington

Wednesday, January 6, 2010 - 4:30 PM
Health Sciences Center, Room K-069

Faculty Sponsor: Ray Monnat

Why Attend?
Molecular Imaging techniques have made significant advances in ability to determine tissue specific biological characteristics quantitatively and non-invasively. PET Imaging is among the most sophisticated of these imaging techniques. PET Imaging uses imaging agents labeled with positron emitters and a special positron imaging device. Our UW group has pioneered development and imaging with new agents that report on tissue perfusion, hypoxia, cell proliferation, multiple drug resistance, receptor status, and many others for applications in cancer and several diseases. Sarcoma is a complex malignancy with a wide range of presentations and clinical behavior. In this seminar, molecular imaging in the example of sarcomas will be presented to highlight basic ideas in understanding the disease process in translational clinical studies.

Janet Eary is a Professor of Radiology in the Division of Nuclear Medicine. She has a joint appointment in Orthopedics and has an adjunct appointment in Pathology. She has pioneered a number of translational studies in Molecular Imaging, high dose radionuclide therapy, and is an expert in imaging clinical trials. Her current research is focused on the use of molecular imaging to stratify outcome risk in cancer patients, and advanced image analysis algorithm development and validation. She enjoys collaborations with investigators from many different disciplines.

Stimulating Myocardial Regeneration with Cardiomyocyte Proliferation Factors

Bernhard Kuhn, M.D.
Associate Professor
Department of Cardiology
Children's Hospital Boston

Wednesday, December 16, 2009 - 4:30 PM
Health Sciences Center, Room K-069

Faculty Sponsor: Chuck Murry

Why Attend?
Dr. Bernhard Kuhn is a physician-scientist with special interests in cardiac regeneration. He received his medical and graduate degrees from the Freie Universitat in Berlin, Germany, in 1999. Dr. Kuhn completed a residency in pediatrics at Yale in 2002 and a clinical and research fellowship in pediatric cardiology at Children's Hospital Boston in 2007. He is Assistant Professor of Pediatrics at Harvard Medical School. Dr. Kuhn's honors include the Young Investigator Award of the American College of Cardiology (Pathology and Physiology) in 2007.

Dr. Kuhn's laboratory at Children's Hospital Boston studies the mechanisms of heart muscle cell proliferation during development and in adult life with the goal of stimulating this process for treating heart failure. Researchers in Dr. Kuhn's laboratory have extensively studied two extracellular factors that stimulate heart muscle cell proliferation and promote heart muscle regeneration: a peptide of periostin, a component of the extracellular matrix, and neuregulin1, a growth factor. Dr. Kuhn's research may provide new regenerative strategies for the treatment of heart failure.

Nuclear Architecture and Aging

Tom Misteli, Ph.D.
Senior Investigator
Cell Biology of Genomes
National Cancer Institute, NIH

Wednesday, December 9, 2009 - 4:30 PM
Health Sciences Center, Room K-069

Faculty Sponsor: Chuck Murry

Why Attend?
Who doesn't care, and at times worry, about aging? Yet, the molecular basis of human aging is one of the least understood fundamental biological processes. A multitude of diverse mechanisms and pathways have been suggested to cause aging. While aging can be readily experimentally studied using animal models, the mechanisms of human aging are more difficult to ascertain. A promising approach is the molecular and cellular interrogation of naturally occurring human pre-mature aging disorders. The most severe premature aging disease is Hutchinson-Gilford Progeria Syndrome. Remarkably, this disease is caused by mutations in a gene encoding major architectural proteins of the cell nucleus. We have analyzed the causes of cellular and organismal defects in this disease and shown that the HGPS mechanisms are also relevant for normal aging. The insights form this rare human disease reveals an intricate interplay between nuclear architecture, stem cell biology and aging.

Tom Misteli is a Senior Investigator at the National Cancer Institute, NIH. He has pioneered the field of genome cell biology by developing imaging approaches to study genomes and gene expression in living cells. His laboratory aims to uncover fundamental principles of higher order genome organization and to apply this knowledge to the development of novel diagnostic and therapeutic strategies for cancer and aging. He has received numerous international awards. He is the Editor-in-Chief of The Journal of Cell Biology and of Current Opinion in Cell Biology.

Evidence Based Management of Liver Cancer: Integration of Research and Clinical Decision Making

Jordi Bruix, M.D.
Associate Professor
Director, Liver Cancer Group
University of Barcelona

Wednesday, December 2, 2009 - 4:30 PM
Health Sciences Center, Room K-069

Faculty Sponsor: Jean Campbell

Why Attend?
Hepatocellular Carcinoma (HCC) is one of the major causes of cancer related death and its incidence is growing worldwide. Treatment of HCC, particularly, the advanced stage disease, is limited and not curative. The combination of these factors has fueled a growing interest in this disease priming research in both its pathogenesis and clinical management. Dr. Jordi Bruix, leader of the Barcelona Clinic Liver Cancer (BCLC) group at the University of Barcelona, has made key contributions in both areas, with a major emphasis on the development of criteria that allow an evidence-based management from diagnosis to therapy. In addition, Dr. Bruix's group through several international collaborations has provided new insight into the molecular profiling of this neoplasm.

Dr. Bruix will discuss his recent work with the phase 3 sorafenib "SHARP" trial, the first successful treatment of advanced-stage HCC and share his critical insight on the implications of recent studies translational studies on the future of HCC research and clinical practice.

Alpha-catenin in Tissue Morphogenesis, Organ Maintenance and Cancer

Valera Vasioukhin
Associate Member
Fred Hutchinson Cancer Research Center

Wednesday, November 18, 2009 - 4:30 PM
Health Sciences Center, Room K-069

Faculty Sponsor: Ray Monnat

Why Attend?
Cadherin-catenin-mediated intercellular adhesion is necessary for the assembly of individual cells into multicellular organisms. Intriguingly, in addition to maintaining intercellular adhesion, cadherin-catenin proteins are also linked to several major developmental signaling pathways. This seminar will discuss our findings on the role and mechanisms of alpha-catenin in mammalian tissue morphogenesis, organ maintenance and cancer.

Merkel Cell Carcinoma and a New Polyomavirus: Mechanisms of Immune Escape by an Often-lethal Skin Malignancy

Paul Nghiem, M.D., Ph.D.
Associate Professor
UW Medicine Dermatology and Pathology

Wednesday, November 4, 2009 - 4:30 PM
Health Sciences Center, Room K-069

Faculty Sponsor: Suzy Dintzis

Why Attend?
Merkel cell carcinoma (MCC) is a neuroendocrine skin cancer associated with advanced age, UV exposure and a new human polyomavirus (integrated in 80% of MCCs). Although 10% of MCC patients are profoundly immune suppressed, 90% have apparently normal immunity. Using genome-wide studies of MCC tumors, we found clues as to immune evasion mechanisms in use by this cancer and associated with outcomes. Using IHC studies on validation sets, we have found evidence of profound intra-tumoral immune suppression in many cases associated with poor outcomes. In contrast, outcomes are excellent in cases with evidence of immune recognition of this tumor. These insights are leading to potential new prognostic tests and translational studies designed to activate immune recognition of this highly antigenic tumor that is currently lethal in about 40% of cases.

Paul Nghiem received his undergraduate degree from Harvard, MD & PhD from Stanford, trained in medicine (Brigham & Women's), dermatology (MGH) and post-doctoral fellowship (Stuart Schreiber's lab in Harvard Chemistry). He moved to Seattle in 2006 and is an Associate Professor of Medicine/Dermatology and Pathology (Adjunct) at UW, and Affiliate Investigator at Fred Hutchinson. He sees patients at the Seattle Cancer Care Alliance and his research lab is at SLU.

The Amazing Liver: New Perspectives on Regeneration and Cancer

Nelson Fausto, M.D.
Professor and Chair
UW Medicine Pathology

Wednesday, October 21, 2009 - 4:30 PM
Health Sciences Center, Room K-069

Faculty Sponsor: Chuck Murry

Why Attend?
Most amphibians and fish can regenerate body parts, but mammals have lost this capacity. A question to be asked is "if they can do it, why cant we." Although we do not have clear answers to this question, the liver is a "yes we can" exception. The mechanisms of liver regeneration in mice and humans are complex and involve an initial priming phase in which hepatocytes respond to components of the innate immune system, enter the cell cycle and become sensitive to the effect of growth factors. In a second phase, hepatocytes progress through the cell cycle under growth factor stimulation, and after passing a restriction point, no longer require external proliferative stimuli. Understanding the cellular and molecular mechanisms of liver regeneration is important both because of its scientific interest but also because it has direct applicability to clinical practice, particularly in liver transplantation. Remarkably, liver regeneration even if repeated does not lead to carcinogenesis. New findings on liver cancer show that the liver stroma plays an essential role in the development of liver tumors, through the regulation of angiogenesis and the production of growth factors required for hepatocyte replication. Cancer development involves the close interaction between the stroma and hepatocytes.

MicroRNAs as Blood-based Cancer Biomarkers

Muneesh Tewari, MD, PhD
Assistant Member
Human Biology
Fred Hutchinson Cancer Research Center

Wednesday, June 3, 2009 - 4:30 PM
Health Sciences Center, K-069

Faculty Sponsor: Ray Monnat, M.D.

Why Attend?
MicroRNAs are small (~22 nt) non-protein-encoding RNAs that regulate target messenger RNAs via sequence-specific base-pairing interactions. MicroRNAs play important roles in diverse biological contexts and disease states. In cancer tissues, alterations in microRNA expression have been shown to be useful biomarkers for disease classification and prognosis. Recently, microRNAs were found to be released by tumor cells into the blood in a cell-free form where they may be useful as blood-based biomarkers for cancer and potentially other diseases. Dr. Tewari will discuss these results and ongoing work in his lab on circulating microRNAs as potential blood-based biomarkers for human cancer.

Dr. Tewari earned a B.A. in Biochemistry from Case Western Reserve University and M.D. and Ph.D. degrees from the University of Michigan. After completing clinical training in Internal Medicine and Medical Oncology, he pursued postdoctoral training in systems biology of genetic and protein interaction networks at Dana-Farber Cancer Institute and Harvard Medical School. Since 2005 he has been on the faculty at the Fred Hutchinson Cancer Research Center, where he is currently an Assistant Member in the Human Biology and Clinical Research Divisions.

Pancreatic Cancer: Genes to Patients

Ralph Hruban, MD
Professor
Pathology/Oncology
John Hopkins University

Wednesday, May 27, 2009 - 4:30 PM
Health Science Center, K-069

Faculty Sponsor: Ray Monnat, M.D.

Why Attend?
Pancreatic cancer is the 4th leading cause of cancer deaths in the United States. Dr. Hruban has been a leader in integrating clinico-pathologic and molecular analyses of human cancer with a special interest in pancreatic carcinoma. Dr. Hruban's research over the past decade has focused on identifying specific genes, mutations and epigenetic profiles that may be determinants of pancreatic cancer risk and progression, and may provide novel insights to improve cancer diagnosis and therapy. His talk will focus on integrating these new data to improve the care of individuals with pancreatic cancer and their families.

Ralph H. Hruban is a Professor of Pathology and Oncology at The Johns Hopkins University School of Medicine. He received his M.D. and completed Residency training at Johns Hopkins, did Fellowship training at Memorial Sloan-Kettering Cancer Center in New York and then returned to Baltimore to join the Johns Hopkins faculty in 1990. Dr. Hruban is currently the Director of The Sol Goldman Pancreatic Cancer Research Center, and Director of the Division of Gastrointestinal/Liver Pathology at Johns Hopkins. In addition to his research Dr. Hruban helped create the Johns Hopkins Pancreatic Cancer Web site (http://pathology.jhu.edu/pancreas), serves on the Scientific Advisory Board of PanCAN and is a Board member or Director at the Monastra, Rolfe and Lustgarten Foundations that are all focused on pancreatic cancer.

Improving Cancer Gene Therapy: Molecular Evolution and the Search for Super Suicide Genes

Margaret Black, Ph.D.
Associate Professor
Pharmaceutical Sciences
Washington State University

Wednesday, May 20, 2009 - 4:30 PM
Health Sciences Center, K-069

Faculty Sponsor: Larry Loeb, M.D., Ph.D.

Why Attend?
Suicide gene therapy employs nucleotide metabolizing enzymes to convert prodrugs to cytotoxic agents as a means to localize toxicity to tumors. Several enzymes involved in pyrimidine and purine anabolism are being exploited as suicide enzymes in combination with pharmacologically relevant analogs. The poor activity the enzymes display towards their respective prodrugs limits the overall therapeutic potential of suicide gene therapy. Dr. Black will discuss molecular engineering methods her lab is using to achieve a more potent cancer cell killing effect.

Dr. Black earned a B.A. in Biology from the University of California, Santa Cruz, and a M.A. in Microbiology from the University of California, Davis and a Ph.D. in Microbiology from Oregon State University. After completion of a postdoctoral fellowship at the University of Washington, she worked at Darwin Molecular Corp. for several years. Since 1998 she has been on the faculty at Washington State University (WSU) in the Department of Pharmaceutical Sciences. Dr. Black is currently the J. Roberts and Marcia Fosberg Distinguished Professor of Pharmacy and is Director of the Pharmacology/Toxicology Graduate Program at WSU.

Signaling Networks in Vascular Morphogenesis and Homeostasis

Luisa Iruela-Arispe, PhD
Professor
Molecular, Cell and Developmental Biology
UCLA

Wednesday, May 13, 2009 - 4:30 PM
Health Sciences Center, K-069

Faculty Sponsor: Charles Murry, M.D., Ph.D.

Why Attend?
Our understanding of vascular fibrosis is limited, particularly at the molecular level. This seminar will discuss how specific molecular alterations in the tunica media result in progressive loss of smooth muscle, expansion of the tunica adventitia and vascular fibrosis. Luisa Iruela-Arispe is currently Professor in the Department of Molecular, Cell and Developmental Biology. She earned her Ph.D. in 1989 from the University of Sao Paulo in Brazil in 1989, but performed her thesis in Dr. Helene Sage at the University of Washington (Dept. of Biological Structure). She continued with Dr. Sage to complete post-doctoral training for four additional years. In 1994, she became Assistant Professor in the Department of Pathology at Harvard Medical School in 1994 and four years later she moved to UCLA, where she is today. Her research focuses on vascular development and pathology.

Mitochondrial Signaling and Dynamics in Health and Disease

Gyorgy Hajnoczky, PhD
Professor
Pathology, Anatomy & Cell Biology
Jefferson Medical University

Wednesday, May 6, 2009 - 4:30 PM
Health Sciences Center , K-069

Faculty Sponsor: Charles Murry, M.D., Ph.D.

Why Attend?
Emerging evidence supports the broad involvement of mitochondria in cell signaling and dynamics. These functions often depend on mitochondrial sensing and responding to calcium. Mitochondrial calcium uptake controls mitochondrial function and cell signaling, while excessive mitochondrial calcium accumulation has been implicated in various diseases.

Gyorgy Hajnoczky is currently a Professor in the Department of Pathology and Cell Biology at Thomas Jefferson University. He earned his M.D. (1987) and Ph.D. (1993) from Semmelweis Medical University in Hungary. In 1991, he joined the lab of Dr. Andrew Thomas at Thomas Jefferson University as a postdoc. He became an independent investigator and was appointed to Assistant Professor in 1995 and to full Professor in 2002. His research focuses on calcium and mitochondrial biology.

Prognostic & Predictive Factors in Surgical Patholgy - - A Critical Assessment

Mark Wick, MD
Professor
Pathology
Univeristy of Virginia

Friday, May 1, 2009 - 4:30 PM
Health Sciences Center, T-639

Faculty Sponsor: Matthew Yeh, M.D., Ph.D.

Why Attend?
Anatomic pathologists are increasingly being asked to evaluate tissue specimens for a growing number of biologically-relevant genes and gene products. These markers are thought to have importance in either prognosis or choice of therapy. However, relatively little attention has been given to the laboratory control mechanisms for assuring the validity of such analyses, and misconceptions also exist as to how they should be applied. This talk considers those issues.

Deciphering the Hereditary Prion Protein Amyloidoses

Bernardino Ghetti, MD
Professor
Pathology & Lab Medicine
Indiana University

Wednesday, April 22, 2009 - 4:30 PM
Health Science Center, K-069

Faculty Sponsor: Montine

7th Annual Alvord Lecture in Neuropathology

The Alvord Lecture honors the scientific and clinical legacy of Professor Emeritus Ellsworth "Buster" Alvord, M.D., as an important pioneer in the field of neuropathology. Dr. Alvord served as Chief of Neoropathology at the University of Washington from 1960 to 2002.

Cellular and Molecular Biology of Natural Killer Cells: From Basic Science to Clinical Implications. A Personal Perspective

Vinay Kumar, MD, PhD
Professor and Chairman
Pathology
University of Chicago Medical School

Wednesday, April 15, 2009 - 4:30 PM
Health Sciences Center, K-069

Faculty Sponsor: UW Medicine Pathology Residents

Why Attend?
Dr Vinay Kumar is the Alice Hogge and Arthur Baer Professor, Chairman of the department of Pathology, and the Executive Vice Dean of the Biologic Sciences Division and Pritzker School of Medicine at the University of Chicago. After completing his medical training in India he completed a combined residency-PhD program at The All India Institute Medical Sciences, New Delhi. Soon thereafter, in 1972, he joined the department of pathology at Boston University School of Medicine, then chaired by Dr Stanley Robbins. In 1982, he moved to UT Southwestern Medical School in Dallas where he was appointed Vernie Stembridge Professor of Pathology in 1992. In 2000 he moved to the University of Chicago to chair the department of Pathology and was named the Executive Vice Dean in 2007.

Dr Kumar has devoted his career to medical education and basic research in immunology. He is the coauthor of Robbins and Cotran Pathologic Basis of Disease and Robbins Basic Pathology, and is currently the senior editor/author of both. These two texts with dozens of translations are the most widely used texts of Pathology worldwide. In 1974, two years after he joined Boston University, he and his colleagues discovered a new class of lymphocytes, later called NK cells, as mediators of resistance to acute leukemia in mice. Since then his laboratory has discovered and defined several NK cell receptors and the pathway of NK cell differentiation from stem cell. These studies have impacted clinical bone marrow transplantation and immunotherapy of tumors.

Genomic Dosage Disorders: Diagnostic Insights and Challenges

Nancy Spinner, PhD
Professor
Genetics in Pediatrics
University of Pennsylvania School of Medicine

Wednesday, April 8, 2009 - 4:30 PM
Health Science Center, K-069

Faculty Sponsor: Christine Disteche, Ph.D.

Why Attend?
Cytogenetics is experiencing a Renaissance, lead by the introduction of array based technology. We've been using high density SNP arrays in the both our clinical Cytogenetics (now CytoGenomics) and research laboratories. The combination of genotyping and intensity data in this platform has revealed a new view of the genome in patients with congenital abnormalities. We've identified new mechanisms of disease, shed light on meiotic and mitotic origins of several types of abnormalities, and diagnosed single gene disorders (dominant and recessive), which contribute to the construction of a gene dosage map. Dr. Spinner received her BS from Brandeis University, PhD in Genetics from UC Berkeley and Fellowship training in Genetics and Cytogenetics at The University of Pennsylvania. She is currently on the Faculty at Penn, in the Departments of Pediatrics and Genetics and she is the Director of the Clinical CytoGenomics Laboratory at The Children's Hospital of Philadelphia.

Gene Networks as Sensors and Drivers of Disease

Eric Schadt, PhD
Executive Scientific Director
Genetics
Rosetta Inpharmatics LLC

Wednesday, April 1, 2009 - 4:30 PM
Health Sciences Center, K-069

Faculty Sponsor: Ray Monnat, M.D.

Why Attend?
Molecular biology has been remarkably successful at revealing mechanisms and interactions between DNA, RNA, and protein biosynthesis, and is beginning to reveal the inner workings of cells. The genomics revolution has extended this approach by providing new tools to take comprehensive 'snapshots' of the molecular states of cells. These data-rich snapshots have allowed us, in turn, to begin to build whole gene networks that define physiological states, and that link and predict how changes in molecular states alter physiology. Dr. Schadt's talk will describe how whole gene networks are constructed, and how they are being used to gain new insights into the origin of human disease, especially the common diseases that are important causes of premature disability and death.

Dr. Schadt received his B.S. in Applied Mathematics/Computer Science from California Polytechnic State University, his M.A. in Pure Mathematics from UCD, and his Ph.D. in Bio-mathematics from UCLA (requiring Ph.D. candidacy in molecular biology and mathematics). He joined Rosetta in 1999, and formed the Genetics/Systems Biology department at Merck when Rosetta was acquired by Merck in 2001. Dr. Schadt is also a UW Affiliate Associate Professor of Biostatistics, and was recently elected a Fellow to the Institute of Systems and Synthetic Biology at Imperial College, London.

Genetic and Epigenetic Regulation of Gene Expression in Normal Development and Diseases of Skeletal Muscle

Stephen Tapscott
Member
Divisions of Human Biology and Clinical Research
Fred Hutchinson Cancer Research Center

Wednesday, March 11, 2009 - 4:30 PM
Health Sciences Center, K-069

Faculty Sponsor: Ray Monnat, M.D.

Why Attend?
Skeletal myogenesis is a model system for defining the molecular mechanisms of regulating a complex program of gene expression in a dynamic system. MyoD is a central factor in this program and has been used to elucidate general rules for how complex cellular programs might evolve and achieve predictable complex behaviors. Dr. Tapscott will discuss his work on the regulation of gene expression in normal myogenesis and in rhabdomyosarcomas.

Dr. Tapscott earned his BA at Hampshire College and MD/PhD from the University of Pennsylvania, where he also completed medical inter,ship and neurology residency. He completed postdoctoral training in molecular biology at the Fred Hutchinson Cancer Research Center and has been a faculty member there since 1991.

Chromatin and G-quadruplex Functions at Telomeres and Beyond

Brad Johnson, MD, PhD
Assistant Professor
Pathology/Lab Medicine
University of Pennsylvania

Wednesday, March 4, 2009 - 4:30 PM
Health Sciences Center, K-069

Faculty Sponsor: Ray Monnat, M.D.

Why Attend?
Telomeres are the physical and functional 'caps' on the ends of chromosomes. Telomere defects are now known to contribute to several degenerative diseases as well as cancer. Dr. Johnson's talk will describe how telomeres are maintained by a combination of chromatin and helicase-dependent recombination pathways. He will also present new evidence for the role of G-quadruplex structures formed by G-rich telomeric DNA in telomere capping and the regulation of transcription.

Dr. Johnson received his BS from Yale, and MD and PhD from Stanford. He did residency training in Clinical Pathology at Brigham and Women's Hospital, and postdoctoral research at MIT before joining the faculty at Penn. Dr. Johnson is currently Assistant Professor of Pathology and Assistant Director of the Clinical Immunology Laboratory at the Hospital of the University of Pennsylvania.

Lost in Translation: Ribosomes in Hematopoiesis

Akiko Shimamura, MD, PhD
Associate Member
Division of Pediatric Hematology/Oncology
Fred Hutchinson Cancer Research Center

Wednesday, February 25, 2009 - 4:30 PM
Health Sciences Center, K-069

Faculty Sponsor: Ray Monnat, M.D.

Why Attend?
Ribosomes have long been considered "housekeeping" organelles whose chief-or sole-function is to translate the information contained in mRNAs into cellular proteins. A surprising recent twist in this story was the identification of ribosomal gene mutations in a group of hematologic disorders characterized by marrow failure and leukemia predisposition. Dr. Shimamura will review the emerging field of ribosomal diseases, and discuss models for disease that arise from ribosomal abnormalities or dysfunction.

Dr. Shimamura received her B.A. from Princeton University and did her M.D. and Ph.D. training at the University of Rochester. She joined the faculty at Harvard after Internship and Residency training at Johns Hopkins, and a Fellowship at the Dana-Farber and Children's Hospital in Boston. She was recruited to the UW in 2007, and is an Associate Member at the Fred Hutchinson in 2008. She directs a research lab at the FHCRC, and is head of the Marrow Failure Clinic at Seattle Children's Hospital.

Translating Pathways to Pancreatic Cancer

Sunil Hingorani, MD, PhD
Assistant Member
Clinical Research and Public Health Sciences Division
Fred Hutchinson Cancer Research Center

Wednesday, February 18, 2009 - 4:30 PM
Health Sciences Center, K-069

Faculty Sponsor: Ray Monnat, M.D.

Why Attend?
Pancreatic cancer is the 4th leading cause of cancer deaths in the U.S. Recent genomic analyses of this common killer have revealed core signaling pathways that are altered in nearly all pancreatic cancers, and thus are new targets for pancreatic cancer diagnosis and therapy. Dr. Hingorani will discuss these findings, and how mouse models can be used to explore the clinical translation of these exciting new results.

Dr. Hingorani received his B.A., M.D. and Ph.D. from Yale. He did internship, residency and fellowship training in Boston at the Brigham & Women's Hospital, Dana-Farber and M.I.T. before joining the faculty at Penn. He was recruited to the Fred Hutchinson and UW in 2005, where he has a research lab and directs the Pancreatic Cancer Specialty Clinic at the Seattle Cancer Care Alliance.

Patient-Specific Models of Glioma Growth and Invasion: Predictive Capability and Clinical Utility

Kristin Swanson, PhD
Research Associate Professor, UW Medicine Pathology
Adjunct Associate Research Professor, Applied Mathematics
University of Washington

Wednesday, February 11, 2009 - 4:30 PM
Health Sciences Center, K-069

Faculty Sponsor: Monnat

Archaeoctyes: Monocytes as Universal Probes for Disease

Stephen Schwartz, MD, PhD
Professor
Pathology
University of Washington

Wednesday, February 4, 2009 - 4:30 PM
Health Sciences Center, K-069

Faculty Sponsor: Monnat

Roles of Transcription in Genomic Stability or Instability

Philip Hanawalt, PhD
Professor
Biological Sciences
Stanford University

Wednesday, January 28, 2009 - 4:30 PM
Health Sciences Center, K-069

Faculty Sponsor: Loeb

Studying Hematopoietic Disease with Genetics & Genomics

Yajuan Liu, PhD
Senior Fellow
Medical Genetics
University of Washington

Wednesday, January 21, 2009 - 4:30 PM
Health Science Bldg, K-069

Faculty Sponsor: Dr. Monnat

"Mitotic Reduction Divisions (Somatic Meiosis) in polyploid Hepatocytes"

Markus Grompe, MD
Professor
Molecular & Medical Genetics and Pediatrics
Oregon Health & Science University

Wednesday, December 10, 2008 - 4:30 PM
Health Science Center, K-069

Faculty Sponsor: Dr. Monnat

FEN1 Mutations Result in Autoimmunity, Chronic Inflammation and Cancers

Binghui Shen, PhD
Professor
Radiation Biology
City of Hope

Wednesday, December 3, 2008 - 4:30 PM
Health Sciences Center, K-069

Faculty Sponsor: Dr. Loeb

“Quantum Dots for Cancer Imaging and Therapeutics�

Xiaohu Gao, PhD
Assistant Professor
Bioengineering
University of Washington

Wednesday, November 19, 2008 - 4:30 PM
Health Science Center, K-069

Faculty Sponsor: Dr. Monnat

Neuroregeneration in the Cerebral Cortex: Impossible and Crazy?

Robert Hevner, M.D., Ph.D.
Professor
Neurological Surgery, Seattle Children's Hospital; and UW Medicine Pathology
University of Washington

Wednesday, November 12, 2008 - 4:30 PM
Health Science Center, K-069

Faculty Sponsor: Dr. Monnat

"Pathogenesis of NASH: new insights from mice with metabolic syndrome"

Geoffrey Farrell, MD
Director/Professor
Gastroenterology and Hepatology
Australian National University

Wednesday, November 5, 2008 - 4:30 PM
Health Sciences Center, K-069

Faculty Sponsor: Dr. Matthew Yeh

"The Instability of Genetic Instability: Pathways Suppressing Mutator Phenotypes in Yeast"

Alan Herr, PhD
Senior Fellow
Pathology
University of Washington

Wednesday, October 29, 2008 - 4:30 PM
Health Sciences Center, K-069

Faculty Sponsor: Dr. Brad Preston

"Control of Cardiovascular Signaling by RGS Proteins"

William Mahoney, PhD
Senior Fellow
Pathology
University of Washington

Wednesday, October 22, 2008 - 4:30 PM
Health Sciences Center, K-069

Faculty Sponsor: Dr. Monnat

Exploring the Interface Between Glial Progenitors and Gliomas

Peter Canoll, MD, PhD
Assistant Professor
Department of Clinical Pathology
Columbia University

Wednesday, October 15, 2008 - 4:30 PM
Health Sciences Center, K-069

Faculty Sponsor: Dr. Tom Montine

Pancreatic Cancer: Emerging Ideas About How the Cancer Forms

Teri Brentnall, MD
Professor
Departments of Medicine and Pathology
University of Washington

Wednesday, October 1, 2008 - 4:30 PM
Health Sciences Center, K-069

Faculty Sponsor: Dr. Rabinovitch

The Blood Brain Barrier in Parkinson's disease: Old Foe or New Friend

Dr. Paul Carvey
Dean
Rush Medical School

Wednesday, February 20, 2008 - 4:30 AM
Health Sciences Building, T639

Faculty Sponsor: Dr. Zhang

Roles of cytokines in regulation of bone mass

Brendan Boyce
Director of Surgical Pathology
Department of Pathology and Laboratory Medicine
University of Rochester Medical Center in New York

Wednesday, June 6, 2007 - 4:30 PM
HSC, K-069

Faculty Sponsor: Dr. Larry True

Membrane Electroporation for Cancer Therapies and Direct Gene Electrotherapy

Dr. Eberhard Neumann
Bielefeld, Germany
Department of Chemistry
University of Bielefeld

Wednesday, May 30, 2007 - 4:30 PM
HSC, K-069

Faculty Sponsor: Dr. Lawrence Loeb
International speaker from Germany

PathPresents: Molecular Diagnosis of Limb-Girdle and Congenital Muscular Dystrophies

Steven A. Moore, M.D., Ph.D.
Co-Director
Wellstone Muscular Dystrophy Research Center
University of Iowa

Wednesday, March 14, 2007 - 4:30 PM
HSC, K-069

Faculty Sponsor: Dr. Hevner
Sponsored by PathPresents.

Path Presents: The Isoprostanes and Related Compounds as Markers and Mediators of Oxidant Stress in Human Disease: New Insights and Current Controversies.

Jason D. Morrow
F. Tremaine Billings Professor of Medicine and Pharmacology
Chief, Division of Clinical Pharmacology
Vanderbilt University School of Medicine

Wednesday, February 7, 2007 - 4:30 PM
HSC, K-069

Faculty Sponsor: Dr. Thomas Montine

Proteomics-Based Strategies to Study Hepatitis C Virus-Related Hepatocellular Carcinoma

Laura Beretta
Associate Member, FHCRC, Affiliate Associate Professor, UW
Pathology
UW - Pathology

Wednesday, June 7, 2006 - 4:00 AM
HSB, K-069

“Global analysis of X chromosome dosage compensation"

Brian Oliver
Section Chief of Developmental Genomics
National Institutes of Health, Bethesda, MD

Wednesday, May 10, 2006 - 4:30 PM
HSB, K-069

Faculty Sponsor: Christine Disteche

**NOTE SPECIAL TIME 1:30PM** "Zebrafish as a model for Cancer, Pigmentation, and Systems Biology"

Keith Cheng
Jake Gittlen Cancer Research Foundation
Penn State College of Medicine

Wednesday, April 26, 2006 - 1:30 PM
HSB, K-069

Faculty Sponsor: Dr. Loeb

“Tough mice and aging: How to survive with a damaged proteome"

Steve Clarke
Professor
Department of Chemistry and Biochemistry
UCLA

Wednesday, May 4, 2005 - 4:30 PM
health science bldg, K-069

Faculty Sponsor: George Martin

Coenzyme Q and Aging: Dr. Jekyll or Mr. Hyde?

Catherine Clarke
Professor
Dept Chemistry and Biochemistry
UCLA

Wednesday, April 27, 2005 - 4:30 PM
Health Science Bldg, K-069

Faculty Sponsor: Tony Parks

"The liver as a model system for cell growth, proliferation, and carcinogenesis"

Jeffrey Albrecht
Associate Professor
Medicine
University of Minnesota

Wednesday, March 9, 2005 - 4:30 PM
Health Science Bldg, K-069

Faculty Sponsor: Tony Parks

“Recombomice" Shed Light on Homologous Recombination in Mammals

Bevin Engelward, Sc.D.
Associate Professor of Molecular Toxicology
Biological Engineering Division
MIT

Wednesday, March 2, 2005 - 4:30 PM
Health Science Bldg, K-069

Faculty Sponsor: Ray Monnat

"DNA Repair: Winning the Race with Replication"

Dr. John Heddle
Professor Emeritus & Senior Scholar
Department of Biology
York University, Toronto, Canada

Wednesday, February 16, 2005 - 4:30 PM
Health Science Bldg, K-069

Faculty Sponsor: Dr. Loeb

Unrepaired G1 DNA breaks can transit S-phase for repair by homologous recombination

Dr Yannick Saintigny

Wednesday, January 12, 2005 - 4:30 PM
Health Sciences Center, T-747

Faculty Sponsor: Dr. Ray Monnat

"Genome Maintenance, Telomeres and RecQ Helicases"

Dr. Judith Campisi
Professor
Lawrence Berkeley Laboratory, Center on the Economics and Demography of Aging
University of California, Berkeley

Wednesday, January 5, 2005 - 3:00 PM
HSB, K-069

Faculty Sponsor: Dr. Rabinovitch

“Defective DNA Damage Responses and Neurodegeneration and Brain Tumors."

Peter McKinnon, Ph.D.
Dept of Genetics,St. Jude Children's Research Hospital, Memphis, TN
Pathology
University of Washington

Wednesday, December 8, 2004 - 4:30 PM
HSB, K-069

Faculty Sponsor: Ray Monnat

The collagen VI muscular dystrophies: new insights into their molecular pathology and genetic basis

Shireen Lamande
Departmenet of Pediatrics
University of Melbourne, Australia

Wednesday, November 17, 2004 - 4:30 PM
Health Sciences Center, Room K-069

Faculty Sponsor: Peter Byers

The Molecular Architecture of Signal Transduction Complexes

John D. Scott
Scientist
Oregon Health Sciences University

Wednesday, October 20, 2004 - 4:30 PM
Health Sciences Center, Room K-069

Faculty Sponsor: Stephen Schwartz

Imaging of Angiogenesis & Lymphangiogenesis in Mouse Models of Disease

Donald McDonald
Professor of Anatomy
University of California, San Francisco

Wednesday, October 6, 2004 - 4:30 PM
Health Sciences Center, Room K-069

Faculty Sponsor: Stephen Schwartz

Evolving Concepts in Soft Tissue Neoplasia

Christopher Fletcher
Professor and Director of Surgical Pathology
Brigham & Women's Hospital
Boston, MA

Wednesday, September 22, 2004 - 4:30 PM
Health Sciences Center, Room T-733

Faculty Sponsor: Dr. Brian Rubin

Seminar Title: TBA

Paul DiCorleto
Director
Lerner Institute
Cleveland Clinic

Wednesday, July 14, 2004 - 4:30 PM
Health Sciences Center, K-069

Faculty Sponsor: Dr. Dan Bowen-Pope

Cardiomyopathy of Dystrophy: Primary Mechanisms and Experimental Therapeutics

Joseph Metzger
Professor
Departments of Physiology and Internal Medicine
University of Michigan

Tuesday, July 13, 2004 - 4:30 PM
Health Sciences Center, Room K-069

Regulation of Cell Growth and Cell Size by the TSC-mTOR Pathway

Kun-Liang Guan
Professor
Department of Biological Chemistry
University of Michigan

Monday, July 12, 2004 - 4:30 PM
Health Sciences Center, K-069

Progression vs Regression of Chronic Kidney Disease: Fact or Fantasy

Agnos Fogo
Professor
Department of Pathology
Vanderbilt University

Thursday, June 17, 2004 - 10:30 AM
Health Sciences Center, Room T-747

Faculty Sponsor: Dr. Charles Alpers

Perlecan Heparan Sulfate in the Control of Vascular Smooth Muscle Cell Proliferation During Development and Disease

Mary Wiser-Evans
Assistant Professor
Departments of Pediatrics and Cell and Developmental Biology
University of Colorado

Tuesday, June 8, 2004 - 4:30 PM
Health Sciences Center, Room K-069

Faculty Sponsor: Michael Reidy

Pleiotropic Effects of HDL and Lysophospholipids in the Vasculature and Heart

Bodo Levkau
Professor
Institute of Pathophysiology
University of Essen

Monday, June 7, 2004 - 4:30 PM
Health Sciences Center, Room K-069

Faculty Sponsor: Elaine Raines

Genetics on Embryonic Stem Cells; A Shortcut for Functional Genomics

Andras Nagy
Professor
Department of Molecular and Medical Genetics
University of Toronto

Wednesday, May 26, 2004 - 4:30 PM
Health Sciences Center, Room K-069

Faculty Sponsor: Dr. Stephen Schwartz

Barking Up the Right Vascular Tree with Sphingosine 1-Phosphate

Timothy Hla
Professor of Cell Biology and of Genetics and Developmental Biology
Director, Center for Vascular Biology
University of Connecticut School of Medicine

Thursday, May 20, 2004 - 4:30 PM
Health Sciences Center, Room T-747

Faculty Sponsor: Dr. Michael Reidy

Histone Methyltransferases in Tumor Suppression

Shi Huang
Associate Professor
The Burnham Institute
La Jolla, California

Wednesday, May 19, 2004 - 4:30 PM
Health Sciences Center, Room K-069

Faculty Sponsor: Dr. Marshall Horwitz

New Entities in Pediatric Renal Neoplasia

Pedram Argani
Assistant Professor
Department of Pathology
Johns Hopkins University School of Medicine

Wednesday, May 12, 2004 - 4:30 PM
Health Sciences Center, K-069

Faculty Sponsor: Dr. Brian Rubin

Identification of Therapeutic Targets in Clinical Practice: Lessons Learned from the HER2 Story

Stuart Schnitt
Professor
Department of Pathology
Harvard Medical School

Wednesday, May 5, 2004 - 4:30 PM
Health Sciences Center, K-069

Faculty Sponsor: Dr. Brian Rubin

Genetic Basis of Aortic Aneurysms and Dissections

Dianna Milewicz
Professor
Department of Medical Genetics
University of Texas Medical School

Wednesday, April 28, 2004 - 4:30 PM
Health Sciences Center, K-069

Faculty Sponsor: Dr. Eileen Mulvihill

Biological Roles of ADAMTS Metalloproteases

Suneel Apte
Associate Professor
Department of Molecular Medicine
CANCELED

Wednesday, April 21, 2004 - 4:30 PM
Health Sciences Center, K-069

Faculty Sponsor: Dr. Ulrike Schwarze

The Fragile X Gene: Distinct Molecular and Neuropathologic Mechanisms Give Rise to Two Separate Syndromes

Paul Hagerman
Professor
Department of Biological Chemistry
University of California, Davis

Monday, March 15, 2004 - 4:30 PM
Health Sciences Center, Room K-069

Faculty Sponsor: Brad Preston and Charles Laird

Development Gone Awry: Genetics and Pathology of Medulloblastoma

Charles Eberhart
Assistant Professor
Department of Pathology
Johns Hopkins University School of Medicine

Wednesday, March 10, 2004 - 4:30 PM
Health Sciences Center, K-069

Faculty Sponsor: Dr. Tom Montine

Vascular Calcification in Chronic Kidney Disease

William G. Goodman
Professor
Department of Medicine
U.C.L.A. School of Medicine

Wednesday, March 3, 2004 - 4:30 PM
Health Sciences Center, K-069

Faculty Sponsor: Dr. Cecilia Giachelli

Utilizing Human Genetics to Understand Vascular Development

Dean Li
Associate Professor
Department of Medicine
University of Utah

Wednesday, February 25, 2004 - 4:30 PM
Health Sciences Center, K-069

Faculty Sponsor: Dr. Stephen Schwartz

Characterization of Cancer-Associated Mutants of DNA Polymerase Beta

Joann Sweasy
Associate Professor
Departments of Therapeutic Radiology and Genetics
Yale University School of Medicine

Wednesday, February 11, 2004 - 4:30 PM
Health Sciences Center, Room K-069

Faculty Sponsor: Dr. Larry Loeb

Mechanism of Lung Adenocarcinoma Induction by Jaagsiekte Sheep Retrovirus and Parallels with Human Lung Cancer

Dusty Miller
Member, FHCRC
Affiliate Professor, Department of Pathology
University of Washington

Wednesday, January 28, 2004 - 4:30 PM
Health Sciences Center, Room K-069

Faculty Sponsor: Dr. Tony Parks

Fundamental Issues in Engineered Vessel Development

Laura Niklason
Assistant Professor
Departments of Biomedical Engineering, Anesthesia and Surgery
Duke University

Friday, January 16, 2004 - 3:30 PM
Health Sciences Center, K-069

Faculty Sponsor: Chuck Murry and Thomas Wight

Prelamin A Processing and Progeria

Stephen Young, M.D.
Senior Investigator
Gladstone Institute of Cardiovascular Disease
University of California, San Francisco

Wednesday, December 17, 2003 - 4:30 PM
Health Sciences Center, K-069

Translational Control in Macrophage Inflammation

Paul L. Fox
Professor of Molecular Medicine
Department of Cell Biology
The Lerner Research Institute, Cleveland Clinic Foundation

Wednesday, December 3, 2003 - 4:30 PM
Health Sciences Center, K-069

Involvement of IKK Alpha in Rank-Mediated Osteoclastogenesis

Michelle Chaisson
Post-Doctoral Fellow
Amgen, Inc.

Wednesday, November 19, 2003 - 4:30 PM
Health Sciences Center, Room K-069

A Murine Model of Intestinal Pseudo-Obstruction

Raj Kapur, M.D., Ph.D.
Associate Professor
Department of Pathology and Department of Laboratories
University of Washington and Children's Hospital and Regional Medical Center

Wednesday, November 5, 2003 - 4:30 PM
Health Sciences Center, Room K-069

Many Genes and Many Tumors: Genetics of Uterine Leiomyomata

Cynthia Morton
Professor
Department of Pathology
Brigham and Women's Hospital, Boston, MA

Wednesday, October 8, 2003 - 4:30 PM
Health Sciences Center, Room K-069

Microscale Systems and Applications for Life-on-a-Chip

Deirdre Meldrum
Professor
Department of Electrical Engineering
University of Washington

Wednesday, June 11, 2003 - 4:30 PM
Health Sciences Center, Room K-069

Biotechnology Drug Discovery in the Post-Human Genome Era

Thomas Bumol, Ph.D.
Vice President
Biotechnology Discovery Research
Lilly Research Laboratories

Thursday, June 5, 2003 - 4:30 PM
Health Sciences Center, T-747

Genetic Chemoprotection of Hematopoietic Stem Cells: Implications for the Treatment of Genetic and Malignant Diseases

Hans-Peter Kiem
Associate Member
Fred Hutchinson Cancer Research Center

Wednesday, May 21, 2003 - 4:30 PM
Health Sciences Center, K-069

Cellular Adaptation to Client Protein Load on the Endoplasmic Reticulum

David Ron, M.D.
Professor
Departments of Medicine and Cell Biology
NYU School of Medicine

Wednesday, May 14, 2003 - 4:30 PM
Health Sciences Center, Room K-069

Yeast and Mouse Models for Exploring Telomere Function in Werner Syndrome

Brad Johnson, M.D., Ph.D.
Assistant Professor
Department of Pathology and Laboratory Medicine
University of Pennsylvania

Wednesday, May 7, 2003 - 4:30 PM
Health Sciences Center, Room K-069

Bacteriophages: Nature’s Self-replicating, Self-limiting Antibiotics

Betty Kutter, Ph.D.
Faculty Member
Department of Biophysics
Evergreen State College

Wednesday, April 30, 2003 - 4:30 PM
HSC, Room K-069

Why Is the Gastric Cardia Such a Big Deal When It Is So Small?

Henry Appelman, M.D.
Professor
Pathology
University of Michigan

Wednesday, April 23, 2003 - 4:30 PM
HSC, Room K-069

Discoidin Domain Receptors (DDRS) - Novel Collagen Receptors in the Vascular System

Michelle Bendeck, Ph.D.
Associate Professor
Laboratory Medicine and Pathobiology
University of Toronto

Wednesday, April 16, 2003 - 4:30 PM
HSC, Room K-069

Sex Chromosome Evolution: A Tale of the Smart, Sexy X Chromosome and the Degenerate Y

Jenny Graves
Professor
Comparative Genomics
Australian National University

Wednesday, April 2, 2003 - 4:30 PM
HSC, Room K-069

The Genetics and Biology of Tumor Suppression by p27/Kipl

Chris Kemp, Ph.D.
Affiliate Associate Professor
Department of Pathology
Fred Hutchinson Cancer Research Center

Wednesday, March 26, 2003 - 4:30 PM
HSC, K-069

Array CGH for High Resolution Analysis of Genomic Aberrations

Dan Pinkel, Ph.D.
Professor
Department of Laboratory Medicine
UCSF

Tuesday, February 25, 2003 - 4:30 PM
Health Sciences Center, Room K-069

Innate Immune Recognition and Response to Microbial Pathogens

Kelly Smith, Ph.D., M.D.
Department of Pathology
University of Washington

Wednesday, February 19, 2003 - 4:30 PM
Health Sciences Center, Room K-069

The Role of Proteolysis in the Pathogenesis of Atherosclerosis

Peter Gough
Research Assistant Professor
Department of Pathology
University of Washington

Wednesday, February 12, 2003 - 4:30 PM
Health Sciences Center, Room K-069

Cellular and Molecualr Mechanisms of Diabetes-accelerated Atherosclerosis

Karin Bornfeldt, Ph.D.
Associate Professor
Department of Pathology
University of Washington

Wednesday, February 5, 2003 - 4:30 PM
Health Sciences Center, Room K-069

Protein Interactions

Stan Fields, Ph.D.
Professor
Departments of Genome Sciences and Medicine
University of Washington

Tuesday, January 21, 2003 - 4:30 PM
Health Sciences Center, T-747

From Gene Expression Patterns to Antibody Diagnostics: A Pharmacogenomics Approach to Cancer Classification and Treatment

Douglas Ross, M.D., Ph.D.
Chief Scientific Officer
Applied Genomics Inc.

Wednesday, December 18, 2002 - 4:30 PM
HSC, K-069

Development of a Gene Expression Array-Based Diagnostic Tool for Lymphoma

Daniel E. Sabath
Associate Professor
Laboratory Medicine
University of Washington

Wednesday, December 4, 2002 - 4:30 PM
HSC, K-069

"Microarray Analysis in Cancer Research: Progress and Promise"

Paul Meltzer, M.D., Ph.D.
Senior Investigator
Cancer Genetics Branch
NIH, National Human Genome Research Institute

Wednesday, November 20, 2002 - 4:30 PM
Health Sciences Center, K-069

Molecular Pathology of the Vascular Form of Ehlers-Danlos Syndrome

Ulrike Schwarze, M.D.
Assistant Professor
Department of Pathology
University of Washington

Wednesday, November 13, 2002 - 4:30 PM
Health Sciences Center, K-069

Single Cell Proteomics

Norm Dovichi
Professor
Department of Chemistry
University of Washington

Wednesday, November 6, 2002 - 4:30 PM
HSC, K-069

DNA Repair Genes Select Stem Cells in Vivo

Stan Gerson, M.D.
Professor and Chief
Hematology/Oncology
Case Western Reserve University

Wednesday, October 30, 2002 - 4:30 PM
HSC, K-069

Multimodality Phenotyping: A Systematic Approach to Understanding Pathogenetic Mechanisms in Cardiovascular Disease

James Scott
Professor
Genetics and Genomics Research Institute
Imperial College of Science

Wednesday, October 16, 2002 - 4:30 PM
Health Sciences Center, K-069

Mouse Models Unravel the p53 Pathway

Gigi Lozano, Ph.D.
Professor and Geneticist
Department of Molecular Genetics
MD Anderson Cancer Center
University of Texas

Wednesday, October 2, 2002 - 4:30 PM
Health Sciences Center, K-069

Cell Growth Survival and Papillogenesis in Ovarian Epithelial Cancer

Santo Nicosia, M.D.
Professor
Interdisciplinary Oncology Program
Moffitt Cancer Center and Research Institute
University of South Florida

Wednesday, July 31, 2002 - 4:30 PM
Health Sciences Center, Room T-747

"Regulation of ErbB Ligand Signaling Networks in Cancer and Diabetes - Role of Ligand Trafficking and Processing"

Peter J. Dempsey, Ph.D.
Principal Scientist
Pacific Northwest Research Institute
Seattle, Washington

Wednesday, June 26, 2002 - 4:30 PM
Health Sciences Center, K-069

"Neurogenesis and Laminar Fate in the Developing Mouse Cerebral Cortex"

Robert Hevner, M.D., Ph.D.
Assistant Professor
Department of Pathology
University of Washington

Wednesday, June 5, 2002 - 4:30 PM
Health Sciences Building, K-069

"Immunohistochemistry in Urologic Tumor Pathology"

Mark Wick, M.D.
Associate Director
Surgical Pathology
University of Virgina Health System

Wednesday, May 29, 2002 - 4:30 PM
Health Sciences Building, K-069

Membranoproliferative/Cryoglobulinemic (Hepatitis C Associcated) Glomerulonephritis: A Disease of Mice and Men

Charles Alpers, M.D.
Professor
Department of Pathology
University of Washington

Wednesday, May 15, 2002 - 4:30 PM
Health Sciences Center,