University of California San Francisco
Helen Diller Family Comprehensive Cancer Center
Matthias Hebrok, PhD

Matthias Hebrok, PhD

Professor in Residence and Director, Diabetes Center, UCSF
Hurlbut-Johnson Distinguished Professor in Diabetes Research

Cancer Center Program Memberships

Cancer Genetics

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

  • 1991-1992
    Diploma thesis, Institute for Immunobiology, Dept. of Tumorbiology, Dr. W. Bessler, advisor
  • 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
  • 1995
    Post-doctoral Research Fellow, Max-Planck-Institute for Immunobiology in Freiburg, Dept. of Developmental Biology
  • 1996-1999
    Postdoctoral Research Fellow, Howard Hughes Medical Institute and Dept. of Molecular and Cellular Biology, Harvard University, Dr. Douglas A. Melton, advisor
  • 1999-2005
    Assistant Professor in Residence, Diabetes Center, University of California, San Francisco
  • 2005-2009
    Associate Professor, Diabetes Center, University of California, San Francisco
  • 2008
    Interim Director, Diabetes Center, University of California, San Francisco
  • 2009-2010
    Associate Director of Research, Diabetes Center, University of California, San Francisco
  • 2009-present
    Professor of Medicine, Diabetes Center, University of California, San Francisco
  • 2010
    Interim Director, Diabetes Center, University of California, San Francisco
  • 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

  1. Jaafar R, Tran S, Shah A, Sun G, Valdearcos M, Marchetti P, Masini M, Swisa A, Giacometti S, Bernal-Mizrachi E, Matveyenko A, Hebrok M, Dor Y, Rutter GA, Koliwad SK, Bhushan A. mTORC1 to AMPK switching underlies ß-cell metabolic plasticity during maturation and diabetes. J Clin Invest. 2019 Jul 02; 130.
    View on PubMed
  2. Spaeth JM, Liu JH, Peters D, Guo M, Osipovich AB, Mohammadi F, Roy N, Bhushan A, Magnuson MA, Hebrok M, Wright CVE, Stein R. The Pdx1 Bound Swi/Snf Chromatin Remodeling Complex Regulates Pancreatic Progenitor Cell Proliferation and Mature Islet ß Cell Function. Diabetes. 2019 Jun 14.
    View on PubMed
  3. Nair GG, Liu JS, Russ HA, Tran S, Saxton MS, Chen R, Juang C, Li ML, Nguyen VQ, Giacometti S, Puri S, Xing Y, Wang Y, Szot GL, Oberholzer J, Bhushan A, Hebrok M. Author Correction: Recapitulating endocrine cell clustering in culture promotes maturation of human stem-cell-derived ß cells. Nat Cell Biol. 2019 06; 21(6):792.
    View on PubMed
  4. Harari N, Sakhneny L, Khalifa-Malka L, Busch A, Hertel KJ, Hebrok M, Landsman L. Pancreatic pericytes originate from the embryonic pancreatic mesenchyme. Dev Biol. 2019 May 01; 449(1):14-20.
    View on PubMed
  5. Nair GG, Liu JS, Russ HA, Tran S, Saxton MS, Chen R, Juang C, Li ML, Nguyen VQ, Giacometti S, Puri S, Xing Y, Wang Y, Szot GL, Oberholzer J, Bhushan A, Hebrok M. Recapitulating endocrine cell clustering in culture promotes maturation of human stem-cell-derived ß cells. Nat Cell Biol. 2019 02; 21(2):263-274.
    View on PubMed
  6. Tsuda M, Fukuda A, Roy N, Hiramatsu Y, Leonhardt L, Kakiuchi N, Hoyer K, Ogawa S, Goto N, Ikuta K, Kimura Y, Matsumoto Y, Takada Y, Yoshioka T, Maruno T, Yamaga Y, Kim GE, Akiyama H, Ogawa S, Wright CV, Saur D, Takaori K, Uemoto S, Hebrok M, Chiba T, Seno H. The BRG1/SOX9 axis is critical for acinar cell-derived pancreatic tumorigenesis. J Clin Invest. 2018 Aug 01; 128(8):3475-3489.
    View on PubMed
  7. Sneddon JB, Tang Q, Stock P, Bluestone JA, Roy S, Desai T, Hebrok M. Stem Cell Therapies for Treating Diabetes: Progress and Remaining Challenges. Cell Stem Cell. 2018 Jun 01; 22(6):810-823.
    View on PubMed
  8. Huang C, Walker EM, Dadi PK, Hu R, Xu Y, Zhang W, Sanavia T, Mun J, Liu J, Nair GG, Tan HYA, Wang S, Magnuson MA, Stoeckert CJ, Hebrok M, Gannon M, Han W, Stein R, Jacobson DA, Gu G. Synaptotagmin 4 Regulates Pancreatic ß Cell Maturation by Modulating the Ca2+ Sensitivity of Insulin Secretion Vesicles. Dev Cell. 2018 05 07; 45(3):347-361.e5.
    View on PubMed
  9. Puri S, Roy N, Russ HA, Leonhardt L, French EK, Roy R, Bengtsson H, Scott DK, Stewart AF, Hebrok M. Replication confers ß cell immaturity. Nat Commun. 2018 02 02; 9(1):485.
    View on PubMed
  10. Faleo G, Russ HA, Wisel S, Parent AV, Nguyen V, Nair GG, Freise JE, Villanueva KE, Szot GL, Hebrok M, Tang Q. Mitigating Ischemic Injury of Stem Cell-Derived Insulin-Producing Cells after Transplant. Stem Cell Reports. 2017 09 12; 9(3):807-819.
    View on PubMed
  11. Chang R, Faleo G, Russ HA, Parent AV, Elledge SK, Bernards DA, Allen JL, Villanueva K, Hebrok M, Tang Q, Desai TA. Nanoporous Immunoprotective Device for Stem-Cell-Derived ß-Cell Replacement Therapy. ACS Nano. 2017 08 22; 11(8):7747-7757.
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  12. von Figura G, Fahrenkrog-Petersen L, Hidalgo-Sastre A, Hartmann D, Hüser N, Schmid RM, Hebrok M, Roy N, Esposito I. Atypical flat lesions derive from pancreatic acinar cells. Pancreatology. 2017 May - Jun; 17(3):350-353.
    View on PubMed
  13. Ivry SL, Sharib JM, Dominguez DA, Roy N, Hatcher SE, Yip-Schneider MT, Schmidt CM, Brand RE, Park WG, Hebrok M, Kim GE, O'Donoghue AJ, Kirkwood KS, Craik CS. Global Protease Activity Profiling Provides Differential Diagnosis of Pancreatic Cysts. Clin Cancer Res. 2017 Aug 15; 23(16):4865-4874.
    View on PubMed
  14. Hebrok M. Designing ß Cells. Cell Metab. 2017 02 07; 25(2):223-224.
    View on PubMed
  15. Liu JS, Hebrok M. All mixed up: defining roles for ß-cell subtypes in mature islets. Genes Dev. 2017 02 01; 31(3):228-240.
    View on PubMed
  16. 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 12 15; 30(24):2669-2683.
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  17. 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. 2017 01; 60(1):35-38.
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  18. 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.
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  19. 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 07 11; 7:11756.
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  20. 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 05; 22(5):497-505.
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