Christine M. Sorenson, PhD
Senior Scientist
Contact the Group
(608) 263-5831
Department of Pediatrics
UW Hospital
600 Highland Ave - H4/4
Madison, WI 53792-4108
The focus of my laboratory is to understand the role apoptotic processes play in kidney and vascular development. We have been focusing on the roles of bcl-2 (anti-apoptotic) and bim (pro-apoptotic) members of bcl-2 family play in these processes. In the absence of bcl-2, mice develop renal hypoplasia/cystic dysplasia. This is due, in part, to decreased ureteric bud branching as a result of aberrant adhesion and migration of renal cells. Furthermore, branching of the renal arteries is decreased suggesting an important role for bcl-2 in normal vascular development and function. In collaboration with Dr. Sheibani’s laboratory, we have shown an essential role for bcl-2 during retinal vascular development and neovascularization. Retinas from the bcl-2 -/- mice exhibited decreased branching and formation of major retinal blood vessels concomitant with reduced number of endothelial cells, pericytes, and capillaries, as well as an inability to undergo ischemia-driven neovascularization. Bim plays an opposing role to bcl-2 in most tissues. We are presently examining bim’s role in kidney development and vascular homeostasis.
Embryonic kidneys rom bcl-2 -/- mice undergo decreased branching morphogenesis.
The research in this laboratory utilizes transgenic mice, as well as endothelial and nephron specific epithelial cells generated from these mice. We have shown that lack of bcl-2 significantly impacts the adhesion and migration properties of renal epithelial and endothelial cells, perhaps through alterations in production of various extracellular matrix (ECM) proteins. We are presently examining how bim expression and its phosphorylation impacts kidney development, postnatal retinal vascular development and retinal ischemia-driven neovascularization. Epithelial and endothelial cell lines are being prepared to examine bim and bcl-2’s role in modulating adhesion, migration and ECM production. These cells are also used to develop cell-based high throughput screening assays for identification of compounds with therapeutic potential. In collaboration with Dr Sheibani’s laboratory, we are also studying the roles thrombospondin-1, a dynamic ECM protein with antiangiogenic activity, play during diabetic nephropathy and retinopathy. The ability of pro- and anti-apoptotic proteins to influence cellular microenvironment could have implications during morphogenesis and differentiation. Alterations in cellular microenvironment may lead to abnormal kidney and vascular development. The information gained from such studies will allow us to design treatment modalities to intervene at earlier stages of disease preventing their development and progression.