Angiogenesis is a highly complex and ordered process whereby new blood vessels are formed from preexisting blood vessels. Angiogenesis is critically important for the development and maintenance of normal tissues, and for the progression of many human diseases including cancer. Because angiogenesis is required to support advanced progression of many diseases, it is thought that halting angiogenesis holds potential for minimizing disease progression. TGF-B is believed to be a powerful regulator of normal and abnormal angiogenesis, but the molecular mechanisms by which TGF-B regulates angiogenesis are largely unknown. The experiments in this proposal are designed to test the hypothesis that TGF-B signaling regulates the expression of genes required for proper blood vessel formation, and that these genes in turn regulate key steps in new blood vessel formation. In testing this hypothesis, we aim to (1) discover novel genes involved in the process of angiogenesis; (2) discover novel TGF-B regulated genes involved in the process of angiogenesis; and (3) characterize identified genes based on their effects on essential steps for proper angiogenesis. In meeting these aims we will discover and characterize novel genes which are important for controlling angiogenesis and may therefore one day, be used as molecular targets for small molecules designed to slow or halt angiogenesis thus improving clinical outcomes for cancer patients.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
5F32CA099321-03
Application #
6918524
Study Section
Special Emphasis Panel (ZRG1-F10 (20))
Program Officer
Lohrey, Nancy
Project Start
2003-08-01
Project End
2006-07-31
Budget Start
2005-08-01
Budget End
2006-07-31
Support Year
3
Fiscal Year
2005
Total Cost
$49,928
Indirect Cost
Name
National Jewish Health
Department
Type
DUNS #
076443019
City
Denver
State
CO
Country
United States
Zip Code
80206
Albig, Allan R; Becenti, Darryl J; Roy, Thessa G et al. (2008) Microfibril-associate glycoprotein-2 (MAGP-2) promotes angiogenic cell sprouting by blocking notch signaling in endothelial cells. Microvasc Res 76:7-14
Albig, Allan R; Roy, Thessa G; Becenti, Darryl J et al. (2007) Transcriptome analysis of endothelial cell gene expression induced by growth on matrigel matrices: identification and characterization of MAGP-2 and lumican as novel regulators of angiogenesis. Angiogenesis 10:197-216
Albig, Allan R; Neil, Jason R; Schiemann, William P (2006) Fibulins 3 and 5 antagonize tumor angiogenesis in vivo. Cancer Res 66:2621-9
Albig, Allan R; Schiemann, William P (2005) Fibulin-5 function during tumorigenesis. Future Oncol 1:23-35
Albig, Allan R; Schiemann, William P (2004) Fibulin-5 antagonizes vascular endothelial growth factor (VEGF) signaling and angiogenic sprouting by endothelial cells. DNA Cell Biol 23:367-79