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
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
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 & Funding
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- Next-generation human liver gene therapySponsor: NIHSponsor ID: DP1DK130689Funding Period:Sep 2021-Jun 2026Principal Investigator
- Targeting AAV vectors to cell types involved in alcohol-induced liver injurySponsor: NIH/NIAAASponsor ID: R01AA026578Funding Period:Sep 2018-May 2023Principal Investigator
- Building a functional biliary system from hepatocytesSponsor: NIH/NIDDKSponsor ID: R01DK107553Funding Period:Sep 2016-Jul 2021Co-Principal Investigator
- Microphysiological systems to interrogate the Islet-Liver-Adipose Axis in normal physiology and Type-2 Diabetes MellitusSponsor: NIH/NIDDKSponsor ID: UG3DK120004Funding Period:Sep 2018-Jul 2020Co-Principal Investigator
- Myofibroblast-to-hepatocyte conversion as a therapy for alcoholic liver diseaseSponsor: NIH/NIAAASponsor ID: R21AA022158Funding Period:Sep 2013-Aug 2015Principal Investigator
- Liver regeneration with stems cells of uniparental originSponsor: NIH/NIDDKSponsor ID: R01DK080852Funding Period:Apr 2008-Aug 2013Co-Principal Investigator
Publications
MOST RECENT PUBLICATIONS FROM A TOTAL OF 70
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- Groeger M, Matsuo K, Heidary Arash E, Pereira A, Le Guillou D, Pino C, Telles-Silva KA, Maher JJ, Hsiao EC, Willenbring H. Modeling and therapeutic targeting of inflammation-induced hepatic insulin resistance using human iPSC-derived hepatocytes and macrophages. Nat Commun. 2023 07 03; 14(1):3902. View in PubMed
- Qi L, Matsuo K, Pereira A, Lee YT, Zhong F, He Y, Zushin PH, Gröger M, Sharma A, Willenbring H, Hsiao EC, Stahl A. Human iPSC-Derived Proinflammatory Macrophages cause Insulin Resistance in an Isogenic White Adipose Tissue Microphysiological System. Small. 2023 08; 19(34):e2203725. View in PubMed
- Laemmle A, Häberle J, Willenbring H. Reply. Hepatology. 2022 04; 75(4):1059-1060. View in PubMed
- Laemmle A, Poms M, Hsu B, Borsuk M, Rüfenacht V, Robinson J, Sadowski MC, Nuoffer JM, Häberle J, Willenbring H. Aquaporin 9 induction in human iPSC-derived hepatocytes facilitates modeling of ornithine transcarbamylase deficiency. Hepatology. 2022 09; 76(3):646-659. View in PubMed
- Lee-Montiel FT, Laemmle A, Charwat V, Dumont L, Lee CS, Huebsch N, Okochi H, Hancock MJ, Siemons B, Boggess SC, Goswami I, Miller EW, Willenbring H, Healy KE. Integrated Isogenic Human Induced Pluripotent Stem Cell-Based Liver and Heart Microphysiological Systems Predict Unsafe Drug-Drug Interaction. Front Pharmacol. 2021; 12:667010. View in PubMed
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In the News
- Willenbring Lab - - June 14, 2018In the medieval ages, alchemists dedicated their lifetimes searching for the formula that would transform ordinary metals into gold. In our bodies, several cases of "cellular alchemy" have been reported. Known as transdifferentiation, this process consists of one specialized cell type transmuting into a different one. Until now, this phenomenon had only been observed in the context of replenishing cells lost from pre-existing structures. Now, UCSF researchers, led by Holger Willenbring, MD, [...]
- Willenbring Lab - - July 08, 2017Holger Willenbring, MD, PhD is the receipient of a Discovery Stage Research Project award from the California Institute for Regenerative Medicine (CIRM). The project "Preclinical development of AAV vector-mediated in vivo hepatic reprogramming of myofibroblasts as a therapy for liver fibrosis" was approved for $1.6M in funding through the Discovery Quest Awards Program, which promotes the discovery of promising new stem cell-based technologies that could be translated to enable broad use and, [...]
- Willenbring Lab - - June 03, 2016UCSF News reports on the research of the Willenbring Lab and others demonstrating in mice that healthy new liver cells could be generated within the organ itself, thus making engraftment unnecessary. The article noted that the very cells that drive liver disease were converted, thereby reducing liver damage and improving liver function simultaneously. The study was recently reported on in a paper published by the journal Cell Stem Cell. Advances in stem cell research have made it possible [...]
- Willenbring Lab - February 23, 2014A recent paper in the journal Nature, reported by UCSF News by a research team including Associate Professor Holger Willenbring, M.D., Ph.D. and Senior Resident Jack Harbell, M.D., a former postdoctoral fellow in the Willenbring lab, reports a new method of cellular reprogramming with potential for treating liver disease: The power of regenerative medicine now allows scientists to transform skin cells into cells that closely resemble heart cells, pancreas cells and even neurons. However, a [...]
- Willenbring Lab - July 16, 2012Intrahepatic bile duct cancer, a rare and deadly form of cancer, known formally as cholangiocarcinoma, has been assumed to derive from cells in the bile ducts of the liver. However, an international team, led by Holger F. Willenbring, M.D., Ph.D., Associate Professor of Developmental and Stem Cell Biology in the Division of Transplant Surgery, Xin Chen, Ph.D.,and other prominent researchers, has shown that the disease actually may develop when hepatocytes, the most common type of liver cell, [...]
- Willenbring Lab - October 22, 2010UCSF scientists have received two large grants from the California Institute for Regenerative Medicine to refine their human embryonic stem cell-based strategies for treating neurological diseases and liver failure. A team led by Mark Zern, MD, of the University of California, Davis, and including co-principal investigator Holger Willenbring, M.D., (pictured left) Assistant Professor of Surgery in the Division of Transplant Surgery at UCSF will use their $5 million grant to develop [...]
- Willenbring Lab - May 14, 2008"International Stem Cell Corporation announced today that its human parthenogenetic stem cell lines will be used in studies aimed at creating liver cells to treat human liver disease. ......Holger Willenbring, MD, UCSF assistant professor of surgery, will direct the research. "The fact that Dr. Willenbring and the University of California at San Francisco are testing the ability of ISCO's human parthenogenetic stem cells to form liver cells is a strong validation of their potential value in [...]
- UCSF Department of Surgery - October 08, 2007Dr. Nancy Ascher and Dr. Holger Willenbring were interviewed by PBS NewsHour correspondent Spencer Michaels about the transformation of embryonic stem cells into new liver cells as a treatment for patients.
