Grant: $16,340 - National Institutes of Health - Jun. 8, 2009
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Award Description: Award Description* DESCRIPTION (provided by applicant): Angiogenesis is essential for normal embryonic development, wound healing, and postischemic tissue repair. However, angiogenesis is also associated with pathological conditions like diabetes, psoriasis, and cancer. The Vascular Endothelial Growth Factors (VEGF) are a family of secreted glycoproteins that control angiogenesis. Recent studies have shown that different strains of inbred mice have a 10-fold range of response to VEGF-induced angiogenesis. Thus, unknown genetic factors must control VEGF responsiveness in mice. The discovery of the genes behind these differences could lead to new angiogenic therapies. We have developed a novel quantitative ex-vivo skin biopsy method to evaluate angiogenic response in the skin of mice. Our method is unique for the following reasons: First, the microvasculature of the skin is well-suited for angiogenic response because it is a primary site of neovascularization in wounding and the skin is a common site of tumor formation. Second, our skin-based approach is performed on multiple samples per individual, decreasing the potential for environmental variation. Finally, because our method is performed on euthanized three-day-old mice, we can perform mapping crosses in an efficient manner. Our preliminary findings have shown that FVB/NJ mice produced the highest amount of blood vessels in our skin biopsy model when compared to C57BL/6J mice. The VEGF hypersensitivity in FVB mice is a recessive trait and based on our preliminary data is likely to be controlled by fewer QTLs than previous approaches designed to map angiogenesis QTLs in mice. We propose to map the QTLs responsible for the novel difference in FVB/NJ skin and define the biological basis of these differences. This work is vital to human health because several therapies designed to control angiogenesis in human disorders are currently in clinical trials based in part on data obtained from mouse models. Our results will improve the validity of testing of mouse models and could lead to the discovery of new therapeutic targets or biomarkers for VEGF mediated therapies.
Project Description: The study will enable the student to complete a required component of her ongoing education without the distraction of a part-time job. In the process of this study she will perform a series of basic wet bench activities related to molecular genetics that include basic DNA isolation, polymerase chain reaction (PCR)-based genotype analysis, and genetic studies to reveal phenotype/genotype interactions. The student isolated genomic DNA from over 200 tissue samples and arranged these samples in diluted aliquots arrayed on plates. She performed PCR reactions using genetic markers from 18 separate assays on each of these samples and recorded the genotype information for all samples tested. A simple regression analysis of the data was performed and significant linkage to two genetic markers was made with phenotype data collected by other members of the lab. This data was presented in a poster at the Genetics and Genomics of Vascular Disease Workshop in Cape cod in September and the student was listed as an author on this report.
Jobs Summary: Summer Intern - Extract genomic DNA from recombinant progeny - New hire (Total jobs reported: 1)
Project Status: More than 50% Completed
This award's data was last updated on Jun. 8, 2009. Help expand these official descriptions using the wiki below.