Chief, Division of Gastroenterology, Massachusetts General Hospital
Robert H. Ebert Associate Professor of Medicine
Associate Professor of Health Sciences and Technology
Harvard Medical School
HMS Director, Harvard-MIT Division of Health Sciences and Technology
Advisory Dean, Irving M. London Society
Associate Member, Broad Institute of MIT and Harvard
Principal Faculty, Harvard Stem Cell Institute
Associate Professor, Department of Medicine, Harvard Medical School
Associate Physician, Gastrointestinal Cancer Center, Dana-Farber Cancer Institute
Associate Physician, Medicine, Brigham And Women's Hospital
Children's Hospital, Dr. Leonard Zon, postdoctoral fellowship
University of Witten/Herdecke, Germany, M.D., Ph.D.
Developmental signaling pathways govern the formation and function of stem cells, thereby holding the key to unlocking the promise of adult tissue regeneration, and to inhibiting cancer development. In our laboratory, we use zebrafish as the primary model to study the liver and explore the regulation of endodermal progenitor cell specification, organ differentiation and growth. We then examine the conserved role of these signaling pathways in regulating tissue growth in surgical and chemical models of liver regeneration and genetic liver cancer models. We also use murine liver injury models to demonstrate evolutionary conservation and relevance for human disease. Our prior work has shown that we can translate our findings from the fish tank to the bedside, as the first clinical trial originating from our findings in the fish has begun to enroll patients.
We have found that the wnt pathway is an important regulator of liver development and regeneration. Recently, we showed that prostaglandin signaling interacts with wnt, offering a chance to therapeutically modify wnt-mediated stem and progenitor cell growth. In an effort to identify new pathways and genes important for liver development, we performed a genetic screen and characterized several mutants with disturbed liver formation. In addition, we are proceeding with a chemical genetic screen to characterize regulators of liver growth. We aim to use these findings and genomic analyses of clinical cohorts to better understand the interaction of regulatory signals that affect liver function and regeneration. The work in our laboratory is directly relevant for developing new treatment options for patients with liver failure and liver cancer.