General Research Goals.

I am vascular biologist with interest in mechanisms that regulate the proliferation and migration of smooth muscle cells. The unwanted growth of these cells is important for the development of intimal hyperplasia. Our laboratory is focused on understanding the molecular and cellular events that are necessary for the development of neointimal lesions.

Current scientific projects.

1- To understand the mechanisms and the regulation of smooth muscle migration. Our past work has shown that the migration of smooth muscle cells from the media into the intima is a critical and necessary step in the development of a neointima. Our studies show that the deletion of MMP-9 gene prevents arterial lesion growth by inhibiting smooth muscle migration as well as proliferation. Current studies are exploring how MMP-9 regulates smooth muscle proliferation.

2- To identify the signal transduction pathways necessary for the expression of cyclin D1 in smooth muscle cells. Unlike medial smooth muscle cells, the replicating cells of neointima activate neither the ERK nor PI3K signal transduction pathways.   Our aim is to discover which signal transduction pathway stimulates cyclin D1 expression and hence entry into the cell cycle. Interesting preliminary suggests that this may be regulated by activation of sphingosine 1-phosphate receptors.

3- To identify the genes that are critical for the growth of neointimal lesions in mice arteries.   The response of mice arteries to injury is strain dependent and while some mice develop a large neointima, others do not. We are currently comparing the molecular and cellular events induced by injury in these two sets of arteries with the ultimate goal to isolate those genes that regulate neointimal lesion formation. These studies include examination of candidate gene expression as well as differential gene expression using DNA arrays.

4- To express siRNAs in mice arteries. The use of siRNAs is a powerful way to interfere with gene expression. We are currently determining if this can be achieved in vivo using a novel electroporation technique or with the use of adeno-associated viral vectors.    Our long term goal is to use siRNAs to selectively block gene expression in arteries of adult animals.

 

Staff

 

Aesim Cho, Ph.D, ResearchScientist, Lab Mgr ascho@u.washington.edu

Tatsu Nakazawa MD, PhD, Post-Doctoral Fellow nakaz@u.washington.edu

Frank Dastvan, Research Scientist va@u.washington.edu

Thao Nguyen, Research Technologist biohzard@u.washington.edu