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Dranoff, Jonathan

Jerome S. Levy Professor of Medicine  Jonathan A. Dranoff, MD, completed his training in Gastroenterology at Yale University in 1999. During his fellowship, he began work on basic studies on the function of bile duct epithelia, the targets of the “cholangiopathies”, including primary biliary cirrhosis, primary sclerosing cholangitis, and biliary atresia. Dr. Dranoff was invited to join the faculty of Yale University in 1999, where he remained until early 2011, rising to the rank of Associate Professor. During his time at Yale, Dr. Dranoff expanded his laboratory efforts to the study of liver fibrosis, and he is one of the few investigators worldwide who has interest in both bile ductular function and basic mechanisms of liver fibrosis. His academic efforts have been recognized internationally, as he has been awarded two NIH/NIDDK R01 awards, an AASLD Advanced Hepatology Fellowship, and an American Heart Association Grant-in-Aid, and has received multiple invitations to present his work at national and international fora. As recognition of his scientific progress, Dr. Dranoff was inducted into the American Society for Clinical Investigation in 2010. Dr. Dranoff currently serves on multiple major committees and advisory panels, including the NIH HBPP Study Section, the Editorial Board of the American Journal of Physiology/GI and Liver Physiology, and as a Councilor of the AGA Institute Council for the Liver & Biliary Section.

Educational Background
Undergraduate: Lehigh University (1986-1989), B.A. 1991

Medical School: Drexel University College of Medicine (1989-1993), M.D. 1993

Residency: Boston University Program in Internal Medicine—1993-1996

Fellowship: Digestive Diseases, Yale University School of Medicine—1996-1999

Societies / Memberships
American Gastroenterological Association

American Federation for Medical Research

American Association for the Study of Liver Disease

American Physiological Society

Gastroenterology Research Group

International Purine Society

American Society for Clinical Investigation

Southern Society for Clinical Investigation

Clinical Interests
Cholestatic Liver Disease

Autoimmune Liver Disease

General Gastroenterology and Hepatology

Research Interests
The Dranoff laboratory has two distinct but intersecting areas of study. The first of these is to try to identify the fundamental mechanisms in the pathogenesis of biliary cirrhosis. Biliary cirrhosis is the end stage of cholestatic liver diseases and is pathologically, clinically, and scientifically distinct from non-biliary cirrhosis. Biliary cirrhosis is also a significant health burden, as it is the cause of one in five cases of liver failure in adults and the majority of liver failure in children. Our work in this area focuses on intercellular signaling between bile duct epithelia, portal fibroblasts, and related cells, as we believe that changes in function between these cells are critical to the pathogenesis of biliary cirrhosis.

Our second overall project is to understand the basic cell biology of hepatic stellate cells, with a strong focus on calcium signaling. Hepatic stellate cells are thought to be the main source of scar producing cells in all forms of cirrhosis, and hormones linked to intracellular calcium signals markedly upregulate functions that contribute to scar formation. We have shown that the basis for intracellular calcium release in these cells is Type I isoform of the inositol trisphosphate receptor, which has a distinct pattern of expression in myofibroblastic or “activated” hepatic stellate cells. We are now working to determine the distinct functions of calcium signals and their downstream effectors in subcellular regions within these fascinating cells.

Current Trainees

1. Michel Fausther, Ph.D., Postdoctoral Fellow

2. Élise Lavoie, Ph.D., Postdoctoral Fellow

3. Allah Haafiz, M.D., Assoc. Prof. of Pediatrics, Arkansas Children’s Hospital

4. Gaurav Syal, M.D., Resident in Internal Medicine

Representative Publications

1.  Dranoff JA and Wells RG. Portal fibroblasts: Underappreciated mediators of liver fibrosis. Hepatology. 51:1438-44 (2010).
2.  Dranoff JA. Bile duct epithelia and portal fibroblasts: Crosstalk signals regulating biliary cirrhosis. In Molecular Pathology of Liver Diseases, S.P. Monga, ed. New York, NY. (2010).
3.  Yu J, Sheung N, Soliman EM, Dranoff JA. Transcriptional regulation of IL-6 in bile duct epithelia by extracellular ATP. Am. J. Physiol. 296:G563-71 (2009).
4.  Soliman EM, Rogrigues M, Gomes DA, Sheung N, Yu J, Amaya MJ, Nathanson MH, Dranoff JA. Intracellular calcium signals regulate growth of hepatic stellate cells via specific effects on cell cycle progression. Cell Calcium. 45:284-292 (2009).
5,  Yu J, Lavoie E, Sheung N, Sevigny J, Dranoff JA. IL-6 downregulates transcription of NTPDase2 via specific promoter elements. Am. J. Physiol. 294:G748-56 (2008).
6.  Kruglov EA, Correa P, Arora G, Nathanson MH, Dranoff JA. Molecular basis for calcium signaling in hepatic stellate cells. Am. J. Physiol.  292:G975-82 (2007).
7.  Kruglov EA, Nathanson RA, Nguyen T, Dranoff JA. Secretion of MCP-1/CCL2 by bile duct epithelia induces myofibroblastic transdifferentiation of portal fibroblasts. Am. J. Physiol. 290:G765-71 (2006).
8.  Jhandier MN, Kruglov EA, Lavoie EG, Sevigny J, and Dranoff JA. Portal Fibroblasts Regluate the Prolferation of Bile Duct Epithelia via Expression of NTPDase2. J. Biol. Chem. 280:22986-92 (2005).
9.  Dranoff JA, Kruglov EA, Toure J, Braun N, Zimmermann H, Jain D, Knowles AF, and Sevigny J, The Ectonucleotidase NTPDase2 is Selectively Down-Regulated in Biliary Fibrosis,  J. Invest. Med. 52:475-82 (2004).
10.  Dranoff JA, Kruglov EA, Robson SC, Braun N, Zimmermann H, Sevigny J. The nucleoside triphosphate diphosphohydrolase NTPDase2/CD39L1 is localized to a novel compartment within the liver. Hepatology 36. 1135-44 (2002).