Christine Sorenson, PhD
Senior Scientist
Contact the Group
(608) 263-5831
Department of Pediatrics
UW Hospital
600 Highland Ave - H4/431
Madison, WI 53792-4108
Sorenson Laboratory
Major Research Interests
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.
Staff
 Cathy K. Grutzmacher Senior Research Specialist |  Margaret E. Morrison Research Assistant |
Active Grants
Bcl-2 and Branching Morphogenesis
National Institutes of Health: RO1
3/1/05-2/28/09
Thrombospondin-1 and Diabetic Nephropathy
American Heart Association
1/1/09-12/31/10
Recent Publications
Sheibani, N., Scheef, E.A., DiMiao, T.A. and Sorenson, C.M. (2007) Bcl-2 Expression Modulates Cell Adhesion and Migration Promoting Branching of Ureteric Bud Cells, J Cell Physiol., 210:616-625.
Wang S., Mehraein F., Sorenson C.M., Darjatmoko S.R., Albert D.M. and Sheibani N. (2007) Calcitriol is a Potent Inhibitor of Retinal Neovascularization, Invest Ophthalm. Vis Science, 48:2327-2334.
Kondo S., Scheef, E.A., Sheibani N., and Sorenson C.M. (2007) PECAM-1 Isoform-Specific Regulation of Kidney Endothelial Cell Migration and Capillary Morphogenesis, Am.J. Physiol., 292:C2070-2083.
Scheef, E.A., Haung, Q., Wang, S., Sorenson, C.M. and Sheibani, N. (2007) Isolation of Corneal Endothelial Cells from Wild Type and Thrombospondin-1 Deficient Mice. Mol Vision, 13:1483-1495.
Sheibani, N., Tang, Y., and Sorenson C.M. (2008) Paxillin’s LD4 Motif Interacts with Bcl-2, J. Cell Physiol., 214:655-661.
Kondo, S., Tang, Y., Scheef, E.A., Sheibani, N. and Sorenson, C.M. (2008) Attenuation of Retinal Endothelial Cell Migration and Capillary Morphogenesis in the Absence of Bcl-2. Am. J. Physiol., 294:C1521-1530.
DiMaio, T.A., Wang, S., Huang, Q., Scheef E.A., Sorenson, C.M. and Sheibani, N. (2008) Attenuation of Retinal Vascular Development and Neovascularization in PECAM-1-Deficient Mice. Dev Biol., 315:72-88.
Kondo, S. and Sorenson, C.M. (2008) Partial Rescue of Renal Hypoplasia/Cystic Dysplasia in Bcl-2 -/- Mice Expressing Bcl-2 in Ureteric Bud Derived Epithelia. Developmental Dynamics, 237:2450-2459.
Haung, Q., Wang, S., Sorenson, C.M., and Sheibani, N. (2008) PEDF-Deficient Mice Exhibit an Enhanced Rate of Retinal Vascular Expansion and are More Sensitive to Hyperoxia-Mediated Vessel Obliteration. Exp. Eye Res., 87:226-241.
Tang, Y., Scheef, E.A., Wang, S., Sorenson, C.M., Marcus, C.B., Jefcoate, C.R. and Sheibani, N. (2009) CYP1B1 Expression Promotes the Proangiogenic Phenotype of Endothelium through Decreased Intracellular Oxidative Stress and Thromobospondin-2 Expression. Blood, 113:744-754.