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Soo Shin, a Biomedical Engineering Ph.D. candidate in the lab of Kimberly Kelly has received a National Science Foundation Graduate Research Fellowship. Project Title: Unexpected gain of function for the scaffolding protein, plectin, due to mislocalization in pancreatic cancer. Research Statement: Pancreatic ductal adenocarcinoma (PDAC) is an intractable clinical problem, typically presenting with metastasis at the time of diagnosis and exhibiting profound resistance to existing therapies. Early detection and complete surgical resection offers the best hope for longer survival. Using phage display and functional proteomics, we recently demonstrated that the cytoskeletal linker protein plectin is a robust biomarker for transition between advanced precursor lesion and invasive PDAC. We showed that plectin, normally cytoplasmic, is localized to the cell surface and is overexpressed in PDAC cells. Plectin has been studied extensively in diseases such as epidermolysis bullosa and muscular dystrophy. However, the biological role of plectin in pancreatic cancer has not been studied. Understanding the biology of aberrant localization of plectin to the cell surface may provide insight into a functional role for this important biomarker of PDAC. The overall goal of this project is to 1) determine the role of plectin in PDAC growth and invasion, 2) determine the potential mechanism by which plectin is mislocalized in PDAC and the effects of plectin mislocalization on PDAC, and 3) delineate the signaling cascades involved in plectin-mediated PDAC growth and invasion.
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