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. Nair GG, Tzanakakis ES, Hebrok M. Emerging routes to the generation of functional ß-cells for diabetes mellitus cell therapy. Nat Rev Endocrinol. 2020 Jun 25.
    View on PubMed
  2. Russell R, Carnese PP, Hennings TG, Walker EM, Russ HA, Liu JS, Giacometti S, Stein R, Hebrok M. Loss of the transcription factor MAFB limits ß-cell derivation from human PSCs. Nat Commun. 2020 Jun 02; 11(1):2742.
    View on PubMed
  3. Zhou X, Nair GG, Russ HA, Belair CD, Li ML, Shveygert M, Hebrok M, Blelloch R. LIN28B Impairs the Transition of hESC-Derived ß Cells from the Juvenile to Adult State. Stem Cell Reports. 2020 01 14; 14(1):9-20.
    View on PubMed
  4. Tong X, Dai C, Walker JT, Nair GG, Kennedy A, Carr RM, Hebrok M, Powers AC, Stein R. Lipid Droplet Accumulation in Human Pancreatic Islets Is Dependent On Both Donor Age and Health. Diabetes. 2020 Mar; 69(3):342-354.
    View on PubMed
  5. Pekrun K, De Alencastro G, Luo QJ, Liu J, Kim Y, Nygaard S, Galivo F, Zhang F, Song R, Tiffany MR, Xu J, Hebrok M, Grompe M, Kay MA. Using a barcoded AAV capsid library to select for clinically relevant gene therapy vectors. JCI Insight. 2019 11 14; 4(22).
    View on PubMed
  6. Chendke GS, Faleo G, Juang C, Parent AV, Bernards DA, Hebrok M, Tang Q, Desai TA. Supporting Survival of Transplanted Stem-Cell-Derived Insulin-Producing Cells in an Encapsulation Device Augmented with Controlled Release of Amino Acids. Adv Biosyst. 2019 Sep; 3(9).
    View on PubMed
  7. Jaafar R, Tran S, Shah AN, 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 07 02; 129(10):4124-4137.
    View on PubMed
  8. 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 09; 68(9):1806-1818.
    View on PubMed
  9. 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.
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  10. 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 05 01; 449(1):14-20.
    View on PubMed
  11. Gopika Nair, Gopika Nair, Holger Russ, Matthias Hebrok. Rapid generation of functional mature pancreatic islet-beta cells from human pluripotent stem cells. Protocol Exchange. 2019 Feb 4.
    View on PubMed
  12. 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
  13. 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 08 01; 128(8):3475-3489.
    View on PubMed
  14. Gaetano Faleo, Casey Ward, Audrey Parent, Gopika Nair, Wenhan Chang, Peter Stock, Matthias Hebrok, Qizhi Tang. Co-Transplant of Parathyroid Gland and Stem Cell-Derived Insulin-Producing Cells Enhances Graft Survival through Release of Pro-Angiogenic and Pro-Survival Factors. Transplantation Journal. 2018 Jul 1; 102(&NA;):s350.
    View on PubMed
  15. 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
  16. 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
  17. 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
  18. 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
  19. 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.
    View on PubMed
  20. Aditi Bhargava, Shinichiro Hagiwara, Sapna Puri, Matthias Hebrok, Gregory Szot, Burcu Hasdemir, Sreenivasan Paruthiyil. Corticotropin-releasing hormone type 2 receptor deficiency impairs pancreatic function in a sex-specific manner. Pancreatology. 2017 Jul 1; 17(3):s8.
    View on PubMed

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