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Resident Research »  Leadership »  Research Committee Members »  Holger Willenbring, M.D., Ph.D.
Holger Willenbring, M.D., Ph.D.

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

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
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  • 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
  • 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
  • Oregon Health & Science University, Portland, Oregon, Department of Molecular and Medical Genetics, 10/2001 -10/2005
  • Liver Cell Therapy
  • LIver Development
  • Liver Regeneration

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. 

ResidentYearsGrant or Funding Source
Hubert Luu, M.D., M.S. 07/2016 - Eli and Edythe Broad Regeneration Medicine and Stem Cell Fellowship
Jack Harbell, M.D. 07/2011 – 06/2013 SUS/Ethicon Resident Research Scholarship
Garrett R. Roll, M.D. 07/2009 – 06/2011 Hepatology Training Grant at UCSF (NIH T32DK060414)
  1. 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
  2. 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
  3. 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
  4. 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
  5. 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
  6. Mattis AN, Willenbring H. A ZFN/piggyBac step closer to autologous liver cell therapy. Hepatology. 2012 Jun; 55(6):2033-5.
    View in: PubMed
  7. 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
  8. 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
  9. 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
  10. Willenbring H. A simple code for installing hepatocyte function. Cell Stem Cell. 2011 Aug 5; 9(2):89-91.
    View in: PubMed
  11. Eckardt S, McLaughlin KJ, Willenbring H. Mouse chimeras as a system to investigate development, cell and tissue function, disease mechanisms and organ regeneration. Cell Cycle. 2011 Jul 1; 10(13):2091-9.
    View in: PubMed
  12. D'Alessio JA, Ng R, Willenbring H, Tjian R. Core promoter recognition complex changes accompany liver development. Proc Natl Acad Sci U S A. 2011 Mar 8; 108(10):3906-11.
    View in: PubMed
  13. Malato Y, Willenbring H. The MAP3K TAK1: a chock block to liver cancer formation. Hepatology. 2010 Oct; 52(4):1506-9.
    View in: PubMed
  14. Espejel S, Roll GR, McLaughlin KJ, Lee AY, Zhang JY, Laird DJ, Okita K, Yamanaka S, Willenbring H. Induced pluripotent stem cell-derived hepatocytes have the functional and proliferative capabilities needed for liver regeneration in mice. J Clin Invest. 2010 Sep; 120(9):3120-6.
    View in: PubMed
  15. Roll GR, Willenbring H. Transplanted nonviable human hepatocytes produce appreciable serum albumin levels in mice. Stem Cell Res. 2010 Nov; 5(3):267-70.
    View in: PubMed
  16. Saunders LR, Sharma AD, Tawney J, Nakagawa M, Okita K, Yamanaka S, Willenbring H, Verdin E. miRNAs regulate SIRT1 expression during mouse embryonic stem cell differentiation and in adult mouse tissues. Aging (Albany NY). 2010 Jul; 2(7):415-31.
    View in: PubMed
  17. Erker L, Azuma H, Lee AY, Guo C, Orloff S, Eaton L, Benedetti E, Jensen B, Finegold M, Willenbring H, Grompe M. Therapeutic liver reconstitution with murine cells isolated long after death. Gastroenterology. 2010 Sep; 139(3):1019-29.
    View in: PubMed
  18. Song G, Sharma AD, Roll GR, Ng R, Lee AY, Blelloch RH, Frandsen NM, Willenbring H. MicroRNAs control hepatocyte proliferation during liver regeneration. Hepatology. 2010 May; 51(5):1735-43.
    View in: PubMed
  19. Willenbring H, Sharma AD, Vogel A, Lee AY, Rothfuss A, Wang Z, Finegold M, Grompe M. Loss of p21 permits carcinogenesis from chronically damaged liver and kidney epithelial cells despite unchecked apoptosis. Cancer Cell. 2008 Jul 8; 14(1):59-67.
    View in: PubMed
  20. Mitchell C, Willenbring H. A reproducible and well-tolerated method for 2/3 partial hepatectomy in mice. Nat Protoc. 2008; 3(7):1167-70.
    View in: PubMed
  21. Ramalho-Santos M, Willenbring H. On the origin of the term "stem cell". Cell Stem Cell. 2007 Jun 7; 1(1):35-8.
    View in: PubMed
  22. Bailey AS, Willenbring H, Jiang S, Anderson DA, Schroeder DA, Wong MH, Grompe M, Fleming WH. Myeloid lineage progenitors give rise to vascular endothelium. Proc Natl Acad Sci U S A. 2006 Aug 29; 103(35):13156-61.
    View in: PubMed
  23. Rizvi AZ, Swain JR, Davies PS, Bailey AS, Decker AD, Willenbring H, Grompe M, Fleming WH, Wong MH. Bone marrow-derived cells fuse with normal and transformed intestinal stem cells. Proc Natl Acad Sci U S A. 2006 Apr 18; 103(16):6321-5.
    View in: PubMed
  24. Vogel A, Aslan JE, Willenbring H, Klein C, Finegold M, Mount H, Thomas G, Grompe M. Sustained phosphorylation of Bid is a marker for resistance to Fas-induced apoptosis during chronic liver diseases. Gastroenterology. 2006 Jan; 130(1):104-19.
    View in: PubMed
  25. Held PK, Al-Dhalimy M, Willenbring H, Akkari Y, Jiang S, Torimaru Y, Olson S, Fleming WH, Finegold M, Grompe M. In vivo genetic selection of renal proximal tubules. Mol Ther. 2006 Jan; 13(1):49-58.
    View in: PubMed
  26. Willenbring H. Therapeutic cell fusion. Br J Surg. 2005 Aug; 92(8):923-4.
    View in: PubMed
  27. Willenbring H, Grompe M. Delineating the hepatocyte's hematopoietic fusion partner. Cell Cycle. 2004 Dec; 3(12):1489-91.
    View in: PubMed
  28. Willenbring H, Bailey AS, Foster M, Akkari Y, Dorrell C, Olson S, Finegold M, Fleming WH, Grompe M. Myelomonocytic cells are sufficient for therapeutic cell fusion in liver. Nat Med. 2004 Jul; 10(7):744-8.
    View in: PubMed
  29. Willenbring H, Grompe M. Embryonic versus adult stem cell pluripotency: in liver only fusion matters. J Assist Reprod Genet. 2003 Oct; 20(10):393-4.
    View in: PubMed
  30. Wang X, Willenbring H, Akkari Y, Torimaru Y, Foster M, Al-Dhalimy M, Lagasse E, Finegold M, Olson S, Grompe M. Cell fusion is the principal source of bone-marrow-derived hepatocytes. Nature. 2003 Apr 24; 422(6934):897-901.
    View in: PubMed
  31. Linnebank M, Tschiedel E, Häberle J, Linnebank A, Willenbring H, Kleijer WJ, Koch HG. Argininosuccinate lyase (ASL) deficiency: mutation analysis in 27 patients and a completed structure of the human ASL gene. Hum Genet. 2002 Oct; 111(4-5):350-9.
    View in: PubMed
  32. Homberger A, Linnebank M, Winter C, Willenbring H, Marquardt T, Harms E, Koch HG. Genomic structure and transcript variants of the human methylenetetrahydrofolate reductase gene. Eur J Hum Genet. 2000 Sep; 8(9):725-9.
    View in: PubMed
  33. Poremba C, Willenbring H, Hero B, Christiansen H, Schäfer KL, Brinkschmidt C, Jürgens H, Böcker W, Dockhorn-Dworniczak B. Telomerase activity distinguishes between neuroblastomas with good and poor prognosis. Ann Oncol. 1999 Jun; 10(6):715-21.
    View in: PubMed
  34. Poremba C, Böcker W, Willenbring H, Schäfer KL, Otterbach F, Bürger H, Diallo R, Dockhorn-Dworniczak B. Telomerase activity in human proliferative breast lesions. Int J Oncol. 1998 Mar; 12(3):641-8.
    View in: PubMed
  35. Hiort O, Sinnecker GH, Willenbring H, Lehners A, Zöllner A, Struve D. Nonisotopic single strand conformation analysis of the 5 alpha-reductase type 2 gene for the diagnosis of 5 alpha-reductase deficiency. J Clin Endocrinol Metab. 1996 Sep; 81(9):3415-8.
    View in: PubMed
  36. Hiort O, Willenbring H, Albers N, Hecker W, Engert J, Dibbelt L, Sinnecker GH. Molecular genetic analysis and human chorionic gonadotropin stimulation tests in the diagnosis of prepubertal patients with partial 5 alpha-reductase deficiency. Eur J Pediatr. 1996 Jun; 155(6):445-51.
    View in: PubMed

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