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Cell Growth/Cancer and VACM-1/CUL5

Project Full Title:

Role of a VACM-1/cul5 Gene Product in the Control of Cell Growth and Cancer development

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Project Description:

This interdisciplinary project will incorporate the disciplines of chemistry and biology. However the project is specifically housed within the Hope College Departments of biology and chemistry .

Research conducted in our lab focuses on elucidating the normal function for VACM-1/cul5 gene which shares sequence homology with cullins, a family of intracellular proteins that regulate diverse signaling pathways in response to changes in the cellular environment. Our work to date indicates that VACM-1/CUL5 protein regulates cellular growth by a mechanism that distinguishes it from growth regulating factors, and from other cullins, and thus suggests a unique biological role for this largely uncharacterized protein. We have shown that both, in cancer cells and in endothelial cells, VACM-1 inhibits growth while expression of VACM-1 mutant has a dominant negative effect on cellular proliferation in vitro. Importantly, expression of VACM-1 mutant converts endothelial cells to the angiogenic phenotype. Consequently, VACM-1 may play a role as a potential novel suppressor of angiogenesis in vivo. Thus, the goal of our recent research is to test the hypothesis that VACM-1 is involved in the regulation of endothelial cell growth, and to identify the mechanism of VACM-1 regulated angiogenesis in vitro. Specifically, we are examining the effects of posttranslational modification and VACM-1 knockout using CRISPR approach on the biological activity of VACM-1 and whether aberrant expression of VACM-1, or expression of mutated VACM-1 may lead to a disease, cancer in particular. Students will be involved in designing experiments that test different aspects of the structure-function properties of VACM-1. Students involved in our research projects will learn experimental procedures that include DNA isolation, site-directed mutagenesis, cell culture, immunocytochemistry, spectrophotometry, fluorescence polarization techniques, polyacrylamide gel analysis and Western blotting. Importantly, students will learn to read, discuss, and question research papers effectively and to prepare scientific manuscripts.

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