Basic Science Research
Brian Lewis, PhD
Dr. Lewis' focus is on the molecular genetics of pancreatic and liver cancers. His lab has generated novel animal models for pancreatic cancer and explores the roles of signaling pathways in disease pathogenesis. Through the analysis of primary tumor specimens, many of the genetic alterations that occur within particular tumor types have been identified. The recent success of targeted cancer therapies, particularly the success of Imatinib (Gleevec), demonstrates that an understanding of the underlying molecular defect(s) can lead to the design of rational, effective therapies. Therefore, one of the overriding goals of his lab is to identify correlations between specific genetic changes, tumor behavior, and signal transduction pathways. With regard to pancreatic cancer, ongoing studies in the lab are aimed at identifying the nature of the transformed cell, identifying the underlying molecular changes that occur in these tumors, and utilizing transgenic animals that express TVA in the ductal or endocrine compartments of the pancreas to identify the effects of oncogene expression in the cell lineages.
Recent work includes:
Morton JP, Klimstra DS, Mongeau ME, Lewis BC. “Trp53 deletion stimulates the formation of metastatic pancreatic tumors.” Am. J. Pathol., in press.
Chen Y-W, Paliwal S, Draheim K, Grossman SR, Lewis BC. (2008) “p19Arf inhibits the invastion of hepatocellular carcinoma cells by binding to CtBP.” Cancer Res. 68: 476-482.
Paliwal S, Kovi RC, Nath B, Chen YW, Lewis BC, Grossman SR. “The alternative reading frame tumor suppressor antagonizes hypoxia-induced cancer cell migration via interaction with the COOH-terminal binding protein corepressor.” Cancer Research. 67(19):9322-9, 2007 Oct 1.
Chen YW, Klimstra DS, Mongeau ME, Tatem JL, Boyartchuk V, Lewis BC. “Loss of p53 and Ink4a/Arf cooperate in a cell autonomous fashion to induce metastasis of hepatocellular carcinoma cells.” Cancer Research. 67(16):7589-96, 2007 Aug 15.
Morton JP, Lewis BC. “Shh signaling and pancreatic cancer: implications for therapy?” Cell Cycle. 6(13):1553-7, 2007 Jul 1.
Morton JP, Mongeau ME, Klimstra DS, Morris JP, Lee YC, Kawaguchi Y, Wright CV, Hebrok M, Lewis BC. “Sonic hedgehog acts at multiple stages during pancreatic tumorigenesis.” Proceedings of the National Academy of Sciences of the United States of America. 104(12):5103-8, 2007 Mar 20.
Lewis BC. “Development of the pancreas and pancreatic cancer.” Endocrinology & Metabolism Clinics of North America. 35(2):397-404, xi, 2006 Jun.
Lewis BC, Klimstra DS, Socci ND, Xu S, Koutcher JA, Varmus HE. “The absence of p53 promotes metastasis in a novel somatic mouse model for hepatocellular carcinoma.” Molecular & Cellular Biology. 25(4):1228-37, 2005 Feb.
Lewis BC, Klimstra DS, Varmus HE. “The c-myc and PyMT oncogenes induce different tumor types in a somatic mouse model for pancreatic cancer.” Genes & Development. 17(24):3127-38, 2003 Dec 15.