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. Reddy NR, Maachi H, Xiao Y, Simic MS, Yu W, Tonai Y, Cabanillas DA, Serrano-Wu E, Pauerstein PT, Tamaki W, Allen GM, Parent AV, Hebrok M, Lim WA. Engineering synthetic suppressor T cells that execute locally targeted immunoprotective programs. Science. 2024 12 06; 386(6726):eadl4793.  View on PubMed
  2. Hendley AM, Ashe S, Urano A, Ng M, Phu TA, Peng XL, Luan C, Finger AM, Jang GH, Kerper NR, Berrios DI, Jin D, Lee J, Riahi IR, Gbenedio OM, Chung C, Roose JP, Yeh JJ, Gallinger S, Biankin AV, O'Kane GM, Ntranos V, Chang DK, Dawson DW, Kim GE, Weaver VM, Raffai RL, Hebrok M. nSMase2-mediated exosome secretion shapes the tumor microenvironment to immunologically support pancreatic cancer. bioRxiv. 2024 Sep 25.  View on PubMed
  3. 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. Author Correction: Genotype tunes pancreatic ductal adenocarcinoma tissue tension to induce matricellular fibrosis and tumor progression. Nat Med. 2024 Mar; 30(3):908.  View on PubMed
  4. Leonhardt L, Hebrok M. KRAS degradation averts PDAC chemoresistance. Nat Cancer. 2024 Mar; 5(3):375-377.  View on PubMed
  5. Puri S, Maachi H, Nair G, Russ HA, Chen R, Pulimeno P, Cutts Z, Ntranos V, Hebrok M. Sox9 regulates alternative splicing and pancreatic beta cell function. Nat Commun. 2024 Jan 18; 15(1):588.  View on PubMed
  6. Audrey M. Hendley, Atsushi Urano, Xianlu L. Peng, Sudipta Ashe, Tuan A. Phu, Martin Ng, Natanya R. Kerper, David I. Berrios, Jonghyun Lee, David Jin, Gun H. Jang, Oghenekevwe M. Gbenedio, Jeroen P. Roose, Jen J. Yeh, Steven Gallinger, Andrew V. Biankin, Vasilis Ntranos, David K. Chang, David W. Dawson, Grace E. Kim, Valerie M. Weaver, Robert L. Raffai, Matthias Hebrok. Abstract A046: nSMase2-generated ceramide promotes PDA aggression through exosome reprogramming of the stroma. Cancer Research. 2024 Jan 16; 84(2_Supplement):a046-a046.  View on PubMed
  7. Cochrane VA, Hebrok M. Stem cell-derived islet therapy: is this the end of the beginning? Nat Rev Endocrinol. 2023 Dec; 19(12):681-682.  View on PubMed
  8. Ashe S, Hebrok M. Role of Cell-Based Therapies in T2D. Semin Nephrol. 2023 05; 43(3):151432.  View on PubMed
  9. 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
  10. 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
  11. 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
  12. Veronica Cochrane, Yini Xiao, Hasna Maachi, Matthias Hebrok. Minimal SC-ß-Cell Properties for Transplantation in Diabetic Patients. Pluripotent Stem Cell Therapy for Diabetes. 2023 Jan 1; 529-545.  View on PubMed
  13. 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
  14. 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 11 08; 22(22):4430-4442.  View on PubMed
  15. 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
  16. 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
  17. 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
  18. 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
  19. 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
  20. 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

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