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.

Research Funding

  • July 29, 2011 - May 31, 2026 - Defining the role of MafA in islet beta cells , Co-Principal Investigator . Sponsor: NIH, Sponsor Award ID: R01DK090570
  • August 15, 2021 - June 30, 2025 - Modulating intrinsic beta cell stress to block diabetes pathogenesis , Principal Investigator . Sponsor: NIH, Sponsor Award ID: R01DK129935
  • September 20, 2018 - July 31, 2023 - Microphysiological systems to interrogate the Islet-Liver-Adipose Axis in normal physiology and Type-2 Diabetes Mellitus , Co-Principal Investigator . Sponsor: NIH, Sponsor Award ID: UH3DK120004
  • May 1, 2015 - July 31, 2023 - Regulation of beta cell identity and dedifferentiation , Principal Investigator . Sponsor: NIH, Sponsor Award ID: R01DK105831
  • September 20, 2019 - May 31, 2023 - Modeling autoimmune pathogenesis and beta cell destruction by T1D immune systems , Co-Principal Investigator . Sponsor: NIH, Sponsor Award ID: U01DK123559
  • September 6, 2021 - August 31, 2022 - Real-time intracellular monitoring of microRNAs in human stem cell-derived insulin producing organoids , Co-Principal Investigator . Sponsor: NIH, Sponsor Award ID: R43DK130034
  • September 1, 2002 - March 31, 2021 - Diabetes Research Center , Co-Investigator . Sponsor: NIH, Sponsor Award ID: P30DK063720
  • July 1, 2016 - December 31, 2020 - Using human stem cell-derived thymic epithelium to remodel T1D immune tolerance , Co-Principal Investigator . Sponsor: NIH, Sponsor Award ID: U01DK107383
  • September 20, 2018 - July 31, 2020 - Microphysiological systems to interrogate the Islet-Liver-Adipose Axis in normal physiology and Type-2 Diabetes Mellitus , Co-Principal Investigator . Sponsor: NIH, Sponsor Award ID: UG3DK120004
  • July 1, 2016 - June 30, 2020 - Using human stem cell-derived thymic epithelium to remodel T1D immune tolerance , Co-Principal Investigator . Sponsor: NIH/NIDDK, Sponsor Award ID: R01DK107383
  • April 3, 2014 - August 31, 2019 - Epigenetic regulation of pancreatic cancer , Principal Investigator . Sponsor: NIH, Sponsor Award ID: R01CA172045
  • September 30, 2015 - July 31, 2019 - Mechanisms of beta cell maturation , Principal Investigator . Sponsor: NIH, Sponsor Award ID: R01DK108666
  • September 1, 2004 - November 30, 2015 - Embryonic signaling pathways in pancreatic cancer , Principal Investigator . Sponsor: NIH, Sponsor Award ID: R01CA112537
  • September 15, 2010 - June 30, 2015 - Expanding beta-cell mass , Co-Principal Investigator . Sponsor: NIH, Sponsor Award ID: U01DK089541
  • December 1, 2001 - February 28, 2014 - Effects of Hedgehog Signaling on Pancreas Organogenesis , Principal Investigator . Sponsor: NIH, Sponsor Award ID: R01DK060533
  • September 30, 2001 - July 31, 2006 - Molecular Control of Pancreatic Islet Development , Co-Investigator . Sponsor: NIH, Sponsor Award ID: U19DK061245

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

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. Cochrane VA, Hebrok M. Stem cell-derived islet therapy: is this the end of the beginning? Nat Rev Endocrinol. 2023 Oct 02.  View on PubMed
  2. Cha J, Tong X, Walker EM, Dahan T, Cochrane VA, Ashe S, Russell R, Osipovich AB, Mawla AM, Guo M, Liu JH, Loyd ZA, Huising MO, Magnuson MA, Hebrok M, Dor Y, Stein R. Species-specific roles for the MAFA and MAFB transcription factors in regulating islet β cell identity. JCI Insight. 2023 08 22; 8(16).  View on PubMed
  3. de Klerk E, Xiao Y, Emfinger CH, Keller MP, Berrios DI, Loconte V, Ekman AA, White KL, Cardone RL, Kibbey RG, Attie AD, Hebrok M. Loss of ZNF148 enhances insulin secretion in human pancreatic β cells. JCI Insight. 2023 06 08; 8(11).  View on PubMed
  4. Chendke GS, Kharbikar BN, Ashe S, Faleo G, Sneddon JB, Tang Q, Hebrok M, Desai TA. Replenishable prevascularized cell encapsulation devices increase graft survival and function in the subcutaneous space. Bioeng Transl Med. 2023 Jul; 8(4):e10520.  View on PubMed
  5. Audrey M. Hendley, Atsushi Urano, Xianlu L. Peng, Sudipta Ashe, Natanya R. Kerper, Tuan A. Phu, Martin Ng, Simone Giacometti, David I. Berrios, Gun H. Jang, Jen J. Yeh, Steven Gallinger, David K. Chang, Andrew V. Biankin, Valerie M. Weaver, Grace E. Kim, David W. Dawson, Robert L. Raffai, Matthias Hebrok. Abstract C051: Ceramide signaling regulates PDA aggression through exosome reprogramming of the stroma. Cancer Research. 2022 Nov 15; 82(22_Supplement):c051-c051.  View on PubMed
  6. Goswami I, de Klerk E, Carnese P, Hebrok M, Healy KE. Multiplexed microfluidic platform for stem-cell derived pancreatic islet β cells. Lab Chip. 2022 Nov 08; 22(22):4430-4442.  View on PubMed
  7. Kerper N, Ashe S, Hebrok M. Pancreatic β-Cell Development and Regeneration. Cold Spring Harb Perspect Biol. 2022 05 27; 14(5).  View on PubMed
  8. Emfinger CH, de Klerk E, Schueler KL, Rabaglia ME, Stapleton DS, Simonett SP, Mitok KA, Wang Z, Liu X, Paulo JA, Yu Q, Cardone RL, Foster HR, Lewandowski SL, Perales JC, Kendziorski CM, Gygi SP, Kibbey RG, Keller MP, Hebrok M, Merrins MJ, Attie AD. β Cell-specific deletion of Zfp148 improves nutrient-stimulated β cell Ca2+ responses. JCI Insight. 2022 05 23; 7(10).  View on PubMed
  9. Chai S, Kim Y, Galivo F, Dorrell C, Wakefield L, Posey J, Ackermann AM, Kaestner KH, Hebrok M, Grompe M. Development of a Beta Cell-Specific Expression Control Element for Recombinant Adeno-Associated Virus. Hum Gene Ther. 2022 08; 33(15-16):789-800.  View on PubMed
  10. Parent AV, Ashe S, Nair GG, Li ML, Chavez J, Liu JS, Zhong Y, Streeter PR, Hebrok M. Development of a scalable method to isolate subsets of stem cell-derived pancreatic islet cells. Stem Cell Reports. 2022 04 12; 17(4):979-992.  View on PubMed
  11. Heller S, Li Z, Lin Q, Geusz R, Breunig M, Hohwieler M, Zhang X, Nair GG, Seufferlein T, Hebrok M, Sander M, Julier C, Kleger A, Costa IG. Transcriptional changes and the role of ONECUT1 in hPSC pancreatic differentiation. Commun Biol. 2021 11 17; 4(1):1298.  View on PubMed
  12. Laura Leonhardt, Lucia Y. Li, David I. Berrios, Sudipta Ashe, Audrey M. Hendley, Grace E. Kim, Matthias Hebrok. Abstract PR-008: Kdm6 demethylases are critical regulators of pancreatic cancer initiation, progression and subtype specification. Cancer Research. 2021 Nov 15; 81(22_Supplement):pr-008-pr-008.  View on PubMed
  13. Philippi A, Heller S, Costa IG, Senée V, Breunig M, Li Z, Kwon G, Russell R, Illing A, Lin Q, Hohwieler M, Degavre A, Zalloua P, Liebau S, Schuster M, Krumm J, Zhang X, Geusz R, Benthuysen JR, Wang A, Chiou J, Gaulton K, Neubauer H, Simon E, Klein T, Wagner M, Nair G, Besse C, Dandine-Roulland C, Olaso R, Deleuze JF, Kuster B, Hebrok M, Seufferlein T, Sander M, Boehm BO, Oswald F, Nicolino M, Julier C, Kleger A. Mutations and variants of ONECUT1 in diabetes. Nat Med. 2021 11; 27(11):1928-1940.  View on PubMed
  14. Parent AV, Faleo G, Chavez J, Saxton M, Berrios DI, Kerper NR, Tang Q, Hebrok M. Selective deletion of human leukocyte antigens protects stem cell-derived islets from immune rejection. Cell Rep. 2021 08 17; 36(7):109538.  View on PubMed
  15. Shaheen R, Gurlin RE, Gologorsky R, Blaha C, Munnangi P, Santandreu A, Torres A, Carnese P, Nair GG, Szot G, Fissell WH, Hebrok M, Roy S. Superporous agarose scaffolds for encapsulation of adult human islets and human stem-cell-derived β cells for intravascular bioartificial pancreas applications. J Biomed Mater Res A. 2021 12; 109(12):2438-2448.  View on PubMed
  16. Hendley AM, Rao AA, Leonhardt L, Ashe S, Smith JA, Giacometti S, Peng XL, Jiang H, Berrios DI, Pawlak M, Li LY, Lee J, Collisson EA, Anderson MS, Fragiadakis GK, Yeh JJ, Ye CJ, Kim GE, Weaver VM, Hebrok M. Single-cell transcriptome analysis defines heterogeneity of the murine pancreatic ductal tree. Elife. 2021 05 19; 10.  View on PubMed
  17. de Klerk E, Hebrok M. Stem Cell-Based Clinical Trials for Diabetes Mellitus. Front Endocrinol (Lausanne). 2021; 12:631463.  View on PubMed
  18. Jacobson EF, Chen Z, Stoukides DM, Nair GG, Hebrok M, Tzanakakis ES. Non-xenogeneic expansion and definitive endoderm differentiation of human pluripotent stem cells in an automated bioreactor. Biotechnol Bioeng. 2021 02; 118(2):979-991.  View on PubMed
  19. Nair GG, Tzanakakis ES, Hebrok M. Emerging routes to the generation of functional β-cells for diabetes mellitus cell therapy. Nat Rev Endocrinol. 2020 09; 16(9):506-518.  View on PubMed
  20. 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 β-cell derivation from human PSCs. Nat Commun. 2020 06 02; 11(1):2742.  View on PubMed

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