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Department of Surgery »  Faculty »  Holger Willenbring, M.D., Ph.D.

Holger Willenbring, M.D., Ph.D.

Associate Professor of Surgery
Member, Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research
Associate Director, Liver Center


Contact Information

(415) 476-2417 Office
(415) 514-2346 Facsimile
willenbringh@stemcell.ucsf.edu

Education

  • Medical University Lübeck, Germany, 10/1989 - 07/1995
  • Harvard Medical School, Boston, MA 08/1995 - 04/1996
  • University of Münster, Germany, 05/1996 - 12/1996

Residencies

  • University of Münster, Germany, Department of Pediatrics, Medical Intern, 02/1997 - 07/1998
  • University of Münster, Germany, Department of Pediatrics, Medical Resident, 08/1998 - 09/2001

Postdoctoral Training

  • Oregon Health & Science University, Portland, Oregon, Department of Molecular and Medical Genetics, 10/2001 -10/2005

Research Interests

  • Liver Cell Therapy
  • LIver Development
  • Liver Regeneration

Research Overview

Our research is aimed at developing new therapies for patients with severe liver diseases. To restore liver function in patients with liver failure, we are working on generating hepatocytes from human pluripotent stem cells or by reprogramming of readily accessible human cell types. To be therapeutically effective, these cells need to replicate both function and the ability to proliferate of primary human hepatocytes. To establish and improve protocols for the production of such cells, we have been working on obtaining a detailed molecular understanding of hepatocyte differentiation and regeneration. For this, we are using mouse models for liver cell lineage tracing developed in our laboratory. In addition, we are using rigorous animal models of human liver failure to test the therapeutic efficacy of our surrogate hepatocytes. While developing novel liver cell therapies is our main focus, we are also using hepatocytes derived from human pluripotent stem cells or by reprogramming to generate in vitro and in vivo liver disease models. Another goal of our laboratory is to determine the origin and follow the fate of liver cancer-initiating cells with the goal to identify the molecular mechanisms that drive liver cancer formation and progression. For this, we are using new mouse models generated in our laboratory. By obtaining an improved understanding of hepatocarcinogenesis, we hope to contribute to the development of strategies for early detection and effective eradication of liver cancer. 

Research Pathways

  • Basic Biomedical Research

Mentored Research Residents

ResidentYearsGrant or Funding Source
Jack Harbell, M.D. 07/2011 – 06/2013 SUS/Ethicon Resident Research Scholarship
Garrett Roll, M.D. 07/2009 – 06/2011 Hepatology Training Grant at UCSF (NIH T32DK060414)
 

Publications

Most recent publications from a total of 37
  1. Zhu S, Rezvani M, Harbell J, Mattis AN, Wolfe AR, Benet LZ, Willenbring H, Ding S. Mouse liver repopulation with hepatocytes generated from human fibroblasts. Nature. 2014 Apr 3; 508(7494):93-7. View in PubMed
  2. Lim L, Balakrishnan A, Huskey N, Jones KD, Jodari M, Ng R, Song G, Riordan J, Anderton B, Cheung ST, Willenbring H, Dupuy A, Chen X, Brown D, Chang AN, Goga A. MicroRNA-494 within an oncogenic microRNA megacluster regulates G1 /S transition in liver tumorigenesis through suppression of mutated in colorectal cancer. Hepatology. 2014 Jan; 59(1):202-15. View in PubMed
  3. Willenbring H, Soto-Gutierrez A. Transplantable liver organoids made from only three ingredients. Cell Stem Cell. 2013 Aug 1; 13(2):139-40. View in PubMed
  4. Ma X, Duan Y, Tschudy-Seney B, Roll G, Behbahan IS, Ahuja TP, Tolstikov V, Wang C, McGee J, Khoobyari S, Nolta JA, Willenbring H, Zern MA. Highly efficient differentiation of functional hepatocytes from human induced pluripotent stem cells. Stem Cells Transl Med. 2013 Jun; 2(6):409-19. View in PubMed
  5. Willenbring H, Grompe M. A therapy for liver failure found in the JNK yard. Cell. 2013 Apr 11; 153(2):283-4. View in PubMed
  6. Fan B, Malato Y, Calvisi DF, Naqvi S, Razumilava N, Ribback S, Gores GJ, Dombrowski F, Evert M, Chen X, Willenbring H. Cholangiocarcinomas can originate from hepatocytes in mice. J Clin Invest. 2012 Aug 1; 122(8):2911-5. View in PubMed
  7. Mattis AN, Willenbring H. A ZFN/piggyBac step closer to autologous liver cell therapy. Hepatology. 2012 Jun; 55(6):2033-5. View in PubMed
  8. Ng R, Song G, Roll GR, Frandsen NM, Willenbring H. A microRNA-21 surge facilitates rapid cyclin D1 translation and cell cycle progression in mouse liver regeneration. J Clin Invest. 2012 Mar 1; 122(3):1097-108. View in PubMed
  9. Rountree CB, Mishra L, Willenbring H. Stem cells in liver diseases and cancer: recent advances on the path to new therapies. Hepatology. 2012 Jan; 55(1):298-306. View in PubMed
  10. Malato Y, Naqvi S, Schürmann N, Ng R, Wang B, Zape J, Kay MA, Grimm D, Willenbring H. Fate tracing of mature hepatocytes in mouse liver homeostasis and regeneration. J Clin Invest. 2011 Dec; 121(12):4850-60. View in PubMed
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