Keynote Speaker

Dr. Steven Leach

The Paul K. Neumann Professor in Pancreatic Cancer

Professor of Surgery, Oncology and Cell Biology

Research Interests

Our laboratory studies genetic and epigenetic regulation of epithelial differentiation in exocrine pancreas, using both mouse and zebrafish model systems. By better understanding factors regulating exocrine differentiation in developing pancreas, we have been able to improve our understanding of abnormal differentiation events occurring during pancreatic tumorigenesis.

Our work has demonstrated that epithelial stem cells in adult and embryonic pancreas are regulated by specific interactions between Notch signaling and the EGF pathway.  Notch is a highly conserved signaling system known to regulate cell fate decisions in a wide variety of adult and embryonic tissues.  We have shown that, during normal pancreatic development, Notch reserves a population of undifferentiated precursor cells by inhibiting the activity of Ptf1a, a basic HLH protein required for formation of exocrine pancreas.  Reflecting this influence, pancreatic differentiation is accelerated in zebrafish embryos with targeted defects in Notch signaling. The importance of this effect is reflected by evidence of Notch pathway activation not only in invasive pancreatic cancer, but also in pancreatic cancer precursor lesions in both mouse and human.  By specifically implicating Notch signaling in the generation of pancreatic cancer precursors, we have identified an important new target for early detection and chemoprevention strategies.

Current studies in the lab are directed towards the following goals:

• Identification and characterization of epithelial progenitor cells in adult and embryonic pancreas
• Identifying novel targets of the pancreas-specific Ptf1 transcriptional complex, using genome-wide screening techniques
• Identification and characterization of novel transcription factors regulating exocrine pancreas development through mutagenesis of the zebrafish genome, using both traditional chemical mutagenesis as well as a novel transposon-mediated gene trapping approach
• Determining the role of microRNA's in the regulation of pancreatic epithelial differentiation
• Functional annotation of the pancreatic cancer genome in zebrafish

Dr. Steven Leach is Professor of Surgery, Oncology and Cell Biology, Vice Chair of the Dept. of Surgery, and the Paul K. Neumann Professor in Pancreatic Cancer at Johns Hopkins University. He is also a member of the McKusick-Nathans Institute for Genetic Medicine, and is on the faculty of both the Cellular and Molecular Medicine and the Human Genetics graduate programs. Dr. Leach went to college at Princeton, followed by medical school at Emory. He subsequently pursued general surgery training at Yale, where he served as Chief Resident in Surgery in 1993. While at Yale, he also completed a two-year research fellowship in pancreatic cell biology, under the direction of Dr. Fred Gorelick. Following an additional fellowship in surgical oncology at the M.D. Anderson Cancer Center, he joined the Vanderbilt faculty in 1995, where he developed a busy clinical practice in general surgical oncology, and also generated NIH support for both his clinical and laboratory research efforts. He moved to Johns Hopkins as the first Paul K. Neumann Professor in 2000. Dr. Leach*s laboratory studies epithelial differentiation in exocrine pancreas, using both mouse and zebrafish model systems. His group is noted for identifying important links between pancreatic development and pancreatic cancer.