Professor in Residence and Director, Diabetes Center, UCSF
Hurlbut-Johnson Distinguished Professor in Diabetes Research
Research Summary
My work focuses on understanding the mechanisms underlying pancreas development and disease, including diabetes and pancreatic cancer. My research on the role of embryonic signaling pathways in these processes has provided a glimpse into how tight regulation of these signaling events is imperative for proper organogenesis, maintenance of organ function, and prevention of pancreatic cancer. My lab has made important insights into how differentiated cells in the exocrine pancreas, namely duct and acinar cells, undergo a process of dedifferentiation during the early stages of neoplasia that can lead to pancreatic ductal adenocarcinoma (PDA), a particularly lethal cancer in humans.
Education
Biological-Technical Assistant (BTA) School, Bückeburg, Germany, Diploma, 1983-1985, Biology
Albert-Ludwigs University, Freiburg, Germany, Diploma/ Master Ph.D., 1986-1992, Cell & Molecular Biology
Max-Planck-Institute for Immunobiology, Freiburg, Germany, 1992-1995, Developmental Biology
Harvard University, Department of Molecular & Cell Biology and Howard Hughes Medical Institute, Cambridge, MA Postdoctoral Training, 1996-1999, Developmental Biology
Professional Experience
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1991-1992
Diploma thesis, Institute for Immunobiology, Dept. of Tumorbiology, Dr. W. Bessler, advisor
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1992-1995
Graduate student, Max-Planck-Institute for Immunobiology, Freiburg, Dept. of Developmental Biology, Dr. Ernst-Martin Füchtbauer, advisor; Dr. Davor Solter, Head of Department
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1995
Post-doctoral Research Fellow, Max-Planck-Institute for Immunobiology in Freiburg, Dept. of Developmental Biology
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1996-1999
Postdoctoral Research Fellow, Howard Hughes Medical Institute and Dept. of Molecular and Cellular Biology, Harvard University, Dr. Douglas A. Melton, advisor
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1999-2005
Assistant Professor in Residence, Diabetes Center, University of California, San Francisco
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2005-2009
Associate Professor, Diabetes Center, University of California, San Francisco
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2008
Interim Director, Diabetes Center, University of California, San Francisco
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2009-2010
Associate Director of Research, Diabetes Center, University of California, San Francisco
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2009-present
Professor of Medicine, Diabetes Center, University of California, San Francisco
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2010
Interim Director, Diabetes Center, University of California, San Francisco
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2010-present
Director, Diabetes Center, University of California, San Francisco
Honors & Awards
- 1994
Graduate Student Research Award of the Hoechst AG, Frankfurt - 1995
Post-doctoral Fellowship from the Max-Planck Society - 1996
Post-doctoral Fellowship from the German Research Society (DFG) - 1997-1999
Howard Hughes Medical Institute Postdoctoral Fellowship - 1999
Sandler Program in Basic Sciences Junior Faculty Start-up Award - 2000
Sandler Award in Basic Sciences - 2000
Career Development Award, Juvenile Diabetes Foundation - 2004
Guest-Professor, University of Ulm, Germany - 2006
Scholar Award, Juvenile Diabetes Research Foundation - 2013-present
Chair, CADO/NIH study section
Selected Publications
- Roy N, Takeuchi KK, Ruggeri JM, Bailey P, Chang D, Li J, Leonhardt L, Puri S, Hoffman MT, Gao S, Halbrook CJ, Song Y, Ljungman M, Malik S, Wright CV, Dawson DW, Biankin AV, Hebrok M, Crawford HC. PDX1 dynamically regulates pancreatic ductal adenocarcinoma initiation and maintenance. Genes Dev. 2016 Dec 15; 30(24):2669-2683.
View on PubMed - Bonifacio E, Mathieu C, Nepom GT, Ziegler AG, Anhalt H, Haller MJ, Harrison LC, Hebrok M, Kushner JA, Norris JM, Peakman M, Powers AC, Todd JA, Atkinson MA. Rebranding asymptomatic type 1 diabetes: the case for autoimmune beta cell disorder as a pathological and diagnostic entity. Diabetologia. 2016 Oct 26.
View on PubMed - Muñoz-Bravo JL, Flores-Martínez A, Herrero-Martin G, Puri S, Taketo MM, Rojas A, Hebrok M, Cano DA. Loss of Pancreas upon Activated Wnt Signaling Is Concomitant with Emergence of Gastrointestinal Identity. PLoS One. 2016; 11(10):e0164714.
View on PubMed - Dorrell C, Schug J, Canaday PS, Russ HA, Tarlow BD, Grompe MT, Horton T, Hebrok M, Streeter PR, Kaestner KH, Grompe M. Human islets contain four distinct subtypes of ß cells. Nat Commun. 2016; 7:11756.
View on PubMed - Laklai H, Miroshnikova YA, Pickup MW, Collisson EA, Kim GE, Barrett AS, Hill RC, Lakins JN, Schlaepfer DD, Mouw JK, LeBleu VS, Roy N, Novitskiy SV, Johansen JS, Poli V, Kalluri R, Iacobuzio-Donahue CA, Wood LD, Hebrok M, Hansen K, Moses HL, Weaver VM. Genotype tunes pancreatic ductal adenocarcinoma tissue tension to induce matricellular fibrosis and tumor progression. Nat Med. 2016 May; 22(5):497-505.
View on PubMed - Hendley AM, Wang YJ, Polireddy K, Alsina J, Ahmed I, Lafaro KJ, Zhang H, Roy N, Savidge SG, Cao Y, Hebrok M, Maitra A, Reynolds AB, Goggins M, Younes M, Iacobuzio-Donahue CA, Leach SD, Bailey JM. p120 Catenin Suppresses Basal Epithelial Cell Extrusion in Invasive Pancreatic Neoplasia. Cancer Res. 2016 Jun 1; 76(11):3351-63.
View on PubMed - Wilcox NS, Rui J, Hebrok M, Herold KC. Life and death of ß cells in Type 1 diabetes: A comprehensive review. J Autoimmun. 2016 Jul; 71:51-8.
View on PubMed - Saini C, Petrenko V, Pulimeno P, Giovannoni L, Berney T, Hebrok M, Howald C, Dermitzakis ET, Dibner C. A functional circadian clock is required for proper insulin secretion by human pancreatic islet cells. Diabetes Obes Metab. 2016 Apr; 18(4):355-65.
View on PubMed - Zhu S, Russ HA, Wang X, Zhang M, Ma T, Xu T, Tang S, Hebrok M, Ding S. Human pancreatic beta-like cells converted from fibroblasts. Nat Commun. 2016; 7:10080.
View on PubMed - Roy N, Hebrok M. Regulation of Cellular Identity in Cancer. Dev Cell. 2015 Dec 21; 35(6):674-84.
View on PubMed - Suriben R, Kaihara KA, Paolino M, Reichelt M, Kummerfeld SK, Modrusan Z, Dugger DL, Newton K, Sagolla M, Webster JD, Liu J, Hebrok M, Dixit VM. ß-Cell Insulin Secretion Requires the Ubiquitin Ligase COP1. Cell. 2015 Dec 3; 163(6):1457-67.
View on PubMed - Russ HA, Landsman L, Moss CL, Higdon R, Greer RL, Kaihara K, Salamon R, Kolker E, Hebrok M. Dynamic Proteomic Analysis of Pancreatic Mesenchyme Reveals Novel Factors That Enhance Human Embryonic Stem Cell to Pancreatic Cell Differentiation. Stem Cells Int. 2016; 2016:6183562.
View on PubMed - Zdravkovic T, Nazor KL, Larocque N, Gormley M, Donne M, Hunkapillar N, Giritharan G, Bernstein HS, Wei G, Hebrok M, Zeng X, Genbacev O, Mattis A, McMaster MT, Krtolica A, Valbuena D, Simón C, Laurent LC, Loring JF, Fisher SJ. Human stem cells from single blastomeres reveal pathways of embryonic or trophoblast fate specification. Development. 2015 Dec 1; 142(23):4010-25.
View on PubMed - Dhawan S, Tschen SI, Zeng C, Guo T, Hebrok M, Matveyenko A, Bhushan A. DNA methylation directs functional maturation of pancreatic ß cells. J Clin Invest. 2015 Jul 1; 125(7):2851-60.
View on PubMed - Russ HA, Parent AV, Ringler JJ, Hennings TG, Nair GG, Shveygert M, Guo T, Puri S, Haataja L, Cirulli V, Blelloch R, Szot GL, Arvan P, Hebrok M. Controlled induction of human pancreatic progenitors produces functional beta-like cells in vitro. EMBO J. 2015 Jul 2; 34(13):1759-72.
View on PubMed - Nair G, Hebrok M. Islet formation in mice and men: lessons for the generation of functional insulin-producing ß-cells from human pluripotent stem cells. Curr Opin Genet Dev. 2015 Jun; 32:171-80.
View on PubMed - Roy N, Malik S, Villanueva KE, Urano A, Lu X, Von Figura G, Seeley ES, Dawson DW, Collisson EA, Hebrok M. Brg1 promotes both tumor-suppressive and oncogenic activities at distinct stages of pancreatic cancer formation. Genes Dev. 2015 Mar 15; 29(6):658-71.
View on PubMed - Huskey NE, Guo T, Evason KJ, Momcilovic O, Pardo D, Creasman KJ, Judson RL, Blelloch R, Oakes SA, Hebrok M, Goga A. CDK1 inhibition targets the p53-NOXA-MCL1 axis, selectively kills embryonic stem cells, and prevents teratoma formation. Stem Cell Reports. 2015 Mar 10; 4(3):374-89.
View on PubMed - Chen NM, Singh G, Koenig A, Liou GY, Storz P, Zhang JS, Regul L, Nagarajan S, Kühnemuth B, Johnsen SA, Hebrok M, Siveke J, Billadeau DD, Ellenrieder V, Hessmann E. NFATc1 Links EGFR Signaling to Induction of Sox9 Transcription and Acinar-Ductal Transdifferentiation in the Pancreas. Gastroenterology. 2015 May; 148(5):1024-1034.e9.
View on PubMed - Singh SK, Chen NM, Hessmann E, Siveke J, Lahmann M, Singh G, Voelker N, Vogt S, Esposito I, Schmidt A, Brendel C, Stiewe T, Gaedcke J, Mernberger M, Crawford HC, Bamlet WR, Zhang JS, Li XK, Smyrk TC, Billadeau DD, Hebrok M, Neesse A, Koenig A, Ellenrieder V. Antithetical NFATc1-Sox2 and p53-miR200 signaling networks govern pancreatic cancer cell plasticity. EMBO J. 2015 Feb 12; 34(4):517-30.
View on PubMed
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