Anti-angiogenic molecules have tremendous potential in the treatment of cancer. Anti-angiogenic therapy has? several benefits over conventional chemotherapy as different tumors can be treated with less toxicity. Most significantly, drug resistance is unlikely. Despite these potential advantages, the utility of current anti-angiogenic agents is limited since the mechanism of action of these proteins is unknown. The PI?s long term objective is to study the mechanism of action of antiangiogenic proteins and to identify the cell surface molecules that interact with these proteins. This proposal focuses on Restin, a C-terminal fragment of the NC1 domain in human collagen XV. This fragment possesses antimigratory function against endothelial cells. This proposal plans to understand the mechanism of action of restin with the following specific aims:? Specific Aim 1: To define the structure-function relationship of restin.? Specific Aim 2: To determine the intracellular signaling events mediated by restin.? Specific Aim 3: To identify and clone the cell surface binding partner(s) receptor for restin.? We will use molecular biology and biochemical techniques to address these aims. Once the mechanism of restin?s action has been elucidated, we will understand better the utility of restin and similar agents as anti-cancer drugs.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Career Transition Award (K22)
Project #
5K22CA095325-02
Application #
7392415
Study Section
Special Emphasis Panel (ZCA1-GRB-J (J1))
Program Officer
Gorelic, Lester S
Project Start
2007-04-03
Project End
2010-03-31
Budget Start
2008-04-07
Budget End
2010-03-31
Support Year
2
Fiscal Year
2008
Total Cost
$159,705
Indirect Cost
Name
Medical College of Wisconsin
Department
Pediatrics
Type
Schools of Medicine
DUNS #
937639060
City
Milwaukee
State
WI
Country
United States
Zip Code
53226
Garnaas, Maija K; Moodie, Karen L; Liu, Miao-liang et al. (2008) Syx, a RhoA guanine exchange factor, is essential for angiogenesis in Vivo. Circ Res 103:710-6