DPC4 function in human pancreatic cancer

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DESCRIPTION (provided by applicant): Dr. Gloria H. Su received her Ph.D. from the University of Chicago. During which, she acquired expertise in the development and analysis of knock-out mice in the laboratory of Dr. M. Celeste Simon. In her postdoctoral training in the molecular genetics laboratory of Dr. Scott E. Kern at The Johns Hopkins University, she identified several tumor suppressor genes important to human pancreatic and biliary adenocarcinomas. She joined the faculty at The Johns Hopkins University in July 2000 in the Department of Pathology, and has since combined her two areas of expertise to focus on the development of mouse models for human pancreatic cancer. Most patients with pancreatic cancer are diagnosed at an advanced stage and the current available treatments are not effective in prolonging the patients' survival. New approaches for early diagnoses and treatment could be extensively studied in animal models, if one were available. The continued discoveries of tumor suppressor genes important in pancreatic cancer have now rendered it possible to construct an animal model to further our understanding of pancreatic tumorigenesis. Creating mouse models that mirror human pancreatic tumorigenesis using knock-out and transgenic techniques is one of Dr. Su's major goals. Here she proposes to study the in vivo impact of a tumor-suppressor gene, DPC4 (SMAD4/MADH4), important for human pancreatic cancer, using conditional knock-out mice and a transgenic mouse line carrying DPC4-specific reporter gene. Dr. Su's position at The Johns Hopkins University will provide her access to important resources such as the Transgenic Mouse Core Laboratory, and the intellectual support of a large group of scientists and clinicians dedicated to curing pancreatic cancer. Among them are her sponsors, Drs. Scott E. Kern and Steven D. Leach, who are internationally recognized researchers in the field of pancreatic cancer. From her sponsors, she will continue to gain valuable lessons on the human genetics, pathology of pancreatic cancer, and murine pancreatic development. The clinical backgrounds and focus of her mentors will also assist Dr. Su in framing her research effort so that they remain directly relevant to human pancreatic cancer. With the enormous support of her mentors, colleagues, and the Department of Pathology, Dr. Su will be able to conduct her research in the richest intellectual and resourceful environment possible for academic and research career development.