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

  • 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/NIDDK, Sponsor Award ID: UH3DK120004
  • May 1, 2015 - July 31, 2023 - Regulation of beta cell identity and dedifferentiation, Principal Investigator. Sponsor: NIH/NIDDK, 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/NIDDK, Sponsor Award ID: U01DK123559
  • 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/NIDDK, Sponsor Award ID: UG3DK120004

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. 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 Nov 17; 4(1):1298.  View on PubMed
  2. 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 Oct 18.  View on PubMed
  3. Kerper N, Ashe S, Hebrok M. Pancreatic β-Cell Development and Regeneration. Cold Spring Harb Perspect Biol. 2021 Sep 27.  View on PubMed
  4. 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 Aug 17; 36(7):109538.  View on PubMed
  5. 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 Dec; 109(12):2438-2448.  View on PubMed
  6. 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
  7. de Klerk E, Hebrok M. Stem Cell-Based Clinical Trials for Diabetes Mellitus. Front Endocrinol (Lausanne). 2021; 12:631463.  View on PubMed
  8. 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
  9. 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
  10. 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
  11. Zhou X, Nair GG, Russ HA, Belair CD, Li ML, Shveygert M, Hebrok M, Blelloch R. LIN28B Impairs the Transition of hESC-Derived β Cells from the Juvenile to Adult State. Stem Cell Reports. 2020 01 14; 14(1):9-20.  View on PubMed
  12. 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 03; 69(3):342-354.  View on PubMed
  13. 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
  14. 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
  15. 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 β-cell metabolic plasticity during maturation and diabetes. J Clin Invest. 2019 07 02; 129(10):4124-4137.  View on PubMed
  16. 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 β-Cell Function. Diabetes. 2019 09; 68(9):1806-1818.  View on PubMed
  17. 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 β cells. Nat Cell Biol. 2019 06; 21(6):792.  View on PubMed
  18. 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
  19. 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
  20. 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 β cells. Nat Cell Biol. 2019 02; 21(2):263-274.  View on PubMed

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