Holger Willenbring, MD, PhD
Professor
Surgery
School of Medicine

Websites

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• Willenbring Lab (willenbringlab.surgery.ucsf.edu)

Grants and Projects

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• Next-generation human liver gene therapy, NIH, 2021-2026
• Microphysiological systems to interrogate the Islet-Liver-Adipose Axis in normal physiology and Type-2 Diabetes Mellitus, NIH, 2018-2023
• Targeting AAV vectors to cell types involved in alcohol-induced liver injury, NIH, 2018-2023
• Building a functional biliary system from hepatocytes, NIH, 2016-2021
• Microphysiological systems to interrogate the Islet-Liver-Adipose Axis in normal physiology and Type-2 Diabetes Mellitus, NIH, 2018-2020
• Myofibroblast-to-hepatocyte conversion as a therapy for alcoholic liver disease, NIH, 2013-2016
• Liver regeneration with stems cells of uniparental origin, NIH, 2008-2013

Publications (71)

Top publication keywords:
LiverInduced Pluripotent Stem CellsDependovirusGenetic VectorsHepatectomyCapsidCholangiocarcinomaBile Duct NeoplasmsLiver RegenerationTyrosinemiasInsulinsCapsid ProteinsOrnithine Carbamoyltransferase Deficiency DiseaseBile DuctsHepatocytes

• Resolving fibrosis by stimulating HSC-dependent extracellular matrix degradation.
  Science translational medicine 2025 Sharma S, Prathigudupu V, Cable C, Serrano LR, Nerella S, Chen A, Hassan G, Lakins J, Valenzuela CL, Tsukui T, Ramamoorthi R, Kim JJ, Willenbring H, Mattis AN, Volk RF, Zaro BW, Coon JJ, Beresis R, …
• Identification of a robust promoter in mouse and human hepatocytes by in vivo biopanning of a barcoded AAV library.
  Molecular therapy : the journal of the American Society of Gene Therapy 2025 Becker J, Domenger C, Choksi P, Krämer C, Baumgartl C, Maiakovska O, Kim JJ, Weinmann J, Huber G, Schmidt F, Thirion C, Müller OJ, Willenbring H, Grimm D
• AAV capsid prioritization in normal and steatotic human livers maintained by machine perfusion.
  Nature biotechnology 2025 Kim JJ, Kurial SNT, Choksi PK, Nunez M, Lunow-Luke T, Bartel J, Driscoll J, Her CL, Dhillon S, Yue W, Murti A, Mao T, Ramos JN, Tiyaboonchai A, Grompe M, Mattis AN, Syed SM, Wang BM, Maher JJ, Roll GR…
• Pervasive and programmed nucleosome distortion patterns on single mammalian chromatin fibers.
  bioRxiv : the preprint server for biology 2025 Yang MG, Richter HJ, Wang S, McNally CP, Harris N, Dhillon S, Maresca M, de Wit E, Willenbring H, Maher J, Goodarzi H, Ramani V
• Adipocyte inflammation is the primary driver of hepatic insulin resistance in a human iPSC-based microphysiological system.
  Nature communications 2024 Qi L, Groeger M, Sharma A, Goswami I, Chen E, Zhong F, Ram A, Healy K, Hsiao EC, Willenbring H, Stahl A

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• Human Hepatocytes Can Give Rise to Intrahepatic Cholangiocarcinomas.
  Gastroenterology 2024 Hsu BY, Driscoll J, Human Cholangiocarcinogenesis Project, Tateno C, Mattis AN, Kelley RK, Willenbring H
• Modeling and therapeutic targeting of inflammation-induced hepatic insulin resistance using human iPSC-derived hepatocytes and macrophages.
  Nature communications 2023 Groeger M, Matsuo K, Heidary Arash E, Pereira A, Le Guillou D, Pino C, Telles-Silva KA, Maher JJ, Hsiao EC, Willenbring H
• Human iPSC-Derived Proinflammatory Macrophages cause Insulin Resistance in an Isogenic White Adipose Tissue Microphysiological System.
  Small (Weinheim an der Bergstrasse, Germany) 2023 Qi L, Matsuo K, Pereira A, Lee YT, Zhong F, He Y, Zushin PH, Gröger M, Sharma A, Willenbring H, Hsiao EC, Stahl A
• Reply.
  Hepatology (Baltimore, Md.) 2022 Laemmle A, Häberle J, Willenbring H
• Aquaporin 9 induction in human iPSC-derived hepatocytes facilitates modeling of ornithine transcarbamylase deficiency.
  Hepatology (Baltimore, Md.) 2021 Laemmle A, Poms M, Hsu B, Borsuk M, Rüfenacht V, Robinson J, Sadowski MC, Nuoffer JM, Häberle J, Willenbring H
• Integrated Isogenic Human Induced Pluripotent Stem Cell-Based Liver and Heart Microphysiological Systems Predict Unsafe Drug-Drug Interaction.
  Frontiers in pharmacology 2021 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
• Induced Pluripotent Stem Cell-derived Hepatocytes From Patients With Nonalcoholic Fatty Liver Disease Display a Disease-specific Gene Expression Profile.
  Gastroenterology 2021 Duwaerts CC, Le Guillou D, Her CL, Phillips NJ, Willenbring H, Mattis AN, Maher JJ
• Emerging cell therapy for biliary diseases.
  Science (New York, N.Y.) 2021 Kurial SNT, Willenbring H
• Transcriptomic Traces of Adult Human Liver Progenitor Cells.
  Hepatology (Baltimore, Md.) 2020 Kurial SNT, Willenbring H
• Broad Distribution of Hepatocyte Proliferation in Liver Homeostasis and Regeneration.
  Cell stem cell 2019 Chen F, Jimenez RJ, Sharma K, Luu HY, Hsu BY, Ravindranathan A, Stohr BA, Willenbring H
• Hepatocyte Nuclear Factor 4 Alpha Activation Is Essential for Termination of Liver Regeneration in Mice.
  Hepatology (Baltimore, Md.) 2019 Huck I, Gunewardena S, Espanol-Suner R, Willenbring H, Apte U
• De novo formation of the biliary system by TGFβ-mediated hepatocyte transdifferentiation.
  Nature 2018 Schaub JR, Huppert KA, Kurial SNT, Hsu BY, Cast AE, Donnelly B, Karns RA, Chen F, Rezvani M, Luu HY, Mattis AN, Rougemont AL, Rosenthal P, Huppert SS, Willenbring H
• Postnatal Organogenesis by Transdifferentiation.
  The FASEB Journal 2018 Holger Willenbring
• Advances in cholangiocarcinoma research: report from the third Cholangiocarcinoma Foundation Annual Conference.
  Journal of gastrointestinal oncology 2016 Abou-Alfa GK, Andersen JB, Chapman W, Choti M, Forbes SJ, Gores GJ, Hong TS, Harding JJ, Vander Heiden MG, Javle M, Kelley RK, Kwong LN, Lowery M, Merrell A, Miyabe K, Rhim A, Saha S, Sia D, …
• In Vivo Hepatic Reprogramming of Myofibroblasts with AAV Vectors as a Therapeutic Strategy for Liver Fibrosis.
  Cell stem cell 2016 Rezvani M, Español-Suñer R, Malato Y, Dumont L, Grimm AA, Kienle E, Bindman JG, Wiedtke E, Hsu BY, Naqvi SJ, Schwabe RF, Corvera CU, Grimm D, Willenbring H
• Assessing the therapeutic potential of lab-made hepatocytes.
  Hepatology (Baltimore, Md.) 2016 Rezvani M, Grimm AA, Willenbring H
• Physiological ranges of matrix rigidity modulate primary mouse hepatocyte function in part through hepatocyte nuclear factor 4 alpha.
  Hepatology (Baltimore, Md.) 2016 Desai SS, Tung JC, Zhou VX, Grenert JP, Malato Y, Rezvani M, Español-Suñer R, Willenbring H, Weaver VM, Chang TT
• A screen in mice uncovers repression of lipoprotein lipase by microRNA-29a as a mechanism for lipid distribution away from the liver.
  Hepatology (Baltimore, Md.) 2014 Mattis AN, Song G, Hitchner K, Kim RY, Lee AY, Sharma AD, Malato Y, McManus MT, Esau CC, Koller E, Koliwad S, Lim LP, Maher JJ, Raffai RL, Willenbring H
• AAV8-mediated in vivo overexpression of miR-155 enhances the protective capacity of genetically attenuated malarial parasites.
  Molecular therapy : the journal of the American Society of Gene Therapy 2014 Hentzschel F, Hammerschmidt-Kamper C, Börner K, Heiss K, Knapp B, Sattler JM, Kaderali L, Castoldi M, Bindman JG, Malato Y, Willenbring H, Mueller AK, Grimm D
• Evidence against a Stem Cell Origin of New Hepatocytes in a Common Mouse Model of Chronic Liver Injury.
  Cell Reports 2014 Johanna R. Schaub, Yann Malato, Coralie Gormond, Holger Willenbring
• Evidence against a stem cell origin of new hepatocytes in a common mouse model of chronic liver injury.
  Cell reports 2014 Schaub JR, Malato Y, Gormond C, Willenbring H
• Brief report: Parthenogenetic embryonic stem cells are an effective cell source for therapeutic liver repopulation.
  Stem cells (Dayton, Ohio) 2014 Espejel S, Eckardt S, Harbell J, Roll GR, McLaughlin KJ, Willenbring H
• Failure to achieve normal metabolic response in non-obese diabetic mice and streptozotocin-induced diabetic mice after transplantation of primary murine hepatocytes electroporated with the human proinsulin gene (p3MTChins).
  Transplantation proceedings 2014 Lee RH, Roll G, Nguyen V, Willenbring H, Tang Q, Kang SM, Stock PG
• Inhibition of microRNA-24 expression in liver prevents hepatic lipid accumulation and hyperlipidemia.
  Hepatology (Baltimore, Md.) 2014 Ng R, Wu H, Xiao H, Chen X, Willenbring H, Steer CJ, Song G
• Mouse liver repopulation with hepatocytes generated from human fibroblasts.
  Nature 2014 Zhu S, Rezvani M, Harbell J, Mattis AN, Wolfe AR, Benet LZ, Willenbring H, Ding S
• Addendum: A reproducible and well-tolerated method for 2/3 partial hepatectomy in mice.
  Nature protocols 2014 Mitchell C, Willenbring H
• Human induced pluripotent stem cell-based microphysiological tissue models of myocardium and liver for drug development.
  Stem cell research & therapy 2013 Mathur A, Loskill P, Hong S, Lee J, Marcus SG, Dumont L, Conklin BR, Willenbring H, Lee LP, Healy KE
• MicroRNA-494 within an oncogenic microRNA megacluster regulates G1/S transition in liver tumorigenesis through suppression of mutated in colorectal cancer.
  Hepatology (Baltimore, Md.) 2013 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
• Transplantable liver organoids made from only three ingredients.
  Cell stem cell 2013 Willenbring H, Soto-Gutierrez A
• Highly efficient differentiation of functional hepatocytes from human induced pluripotent stem cells.
  Stem cells translational medicine 2013 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
• A therapy for liver failure found in the JNK yard.
  Cell 2013 Willenbring H, Grompe M
• Akt/Notch activation drives rapid cholangiocarcinoma development originating from mature hepatocytes in the mouse.
  Zeitschrift für Gastroenterologie 2013 M Evert, B Fan, Y Malato, S Ribback, F Dombrowski, H Willenbring, X Chen, DF Calvisi
• Cholangiocarcinomas can originate from hepatocytes in mice.
  The Journal of clinical investigation 2012 Fan B, Malato Y, Calvisi DF, Naqvi S, Razumilava N, Ribback S, Gores GJ, Dombrowski F, Evert M, Chen X, Willenbring H
• A ZFN/piggyBac step closer to autologous liver cell therapy.
  Hepatology (Baltimore, Md.) 2012 Mattis AN, Willenbring H
• A microRNA-21 surge facilitates rapid cyclin D1 translation and cell cycle progression in mouse liver regeneration.
  The Journal of clinical investigation 2012 Ng R, Song G, Roll GR, Frandsen NM, Willenbring H
• Stem cells in liver diseases and cancer: recent advances on the path to new therapies.
  Hepatology (Baltimore, Md.) 2012 Rountree CB, Mishra L, Willenbring H
• Fate tracing of mature hepatocytes in mouse liver homeostasis and regeneration.
  The Journal of clinical investigation 2011 Malato Y, Naqvi S, Schürmann N, Ng R, Wang B, Zape J, Kay MA, Grimm D, Willenbring H
• A simple code for installing hepatocyte function.
  Cell stem cell 2011 Willenbring H
• Mouse chimeras as a system to investigate development, cell and tissue function, disease mechanisms and organ regeneration.
  Cell cycle (Georgetown, Tex.) 2011 Eckardt S, McLaughlin KJ, Willenbring H
• Core promoter recognition complex changes accompany liver development.
  Proceedings of the National Academy of Sciences of the United States of America 2011 D'Alessio JA, Ng R, Willenbring H, Tjian R
• The MAP3K TAK1: a chock block to liver cancer formation.
  Hepatology (Baltimore, Md.) 2010 Malato Y, Willenbring H
• Induced pluripotent stem cell-derived hepatocytes have the functional and proliferative capabilities needed for liver regeneration in mice.
  The Journal of clinical investigation 2010 Espejel S, Roll GR, McLaughlin KJ, Lee AY, Zhang JY, Laird DJ, Okita K, Yamanaka S, Willenbring H
• Transplanted nonviable human hepatocytes produce appreciable serum albumin levels in mice.
  Stem cell research 2010 Roll GR, Willenbring H
• miRNAs regulate SIRT1 expression during mouse embryonic stem cell differentiation and in adult mouse tissues.
  Aging 2010 Saunders LR, Sharma AD, Tawney J, Nakagawa M, Okita K, Yamanaka S, Willenbring H, Verdin E
• Therapeutic liver reconstitution with murine cells isolated long after death.
  Gastroenterology 2010 Erker L, Azuma H, Lee AY, Guo C, Orloff S, Eaton L, Benedetti E, Jensen B, Finegold M, Willenbring H, Grompe M
• MicroRNAs control hepatocyte proliferation during liver regeneration.
  Hepatology (Baltimore, Md.) 2010 Song G, Sharma AD, Roll GR, Ng R, Lee AY, Blelloch RH, Frandsen NM, Willenbring H
• Loss of p21 permits carcinogenesis from chronically damaged liver and kidney epithelial cells despite unchecked apoptosis.
  Cancer cell 2008 Willenbring H, Sharma AD, Vogel A, Lee AY, Rothfuss A, Wang Z, Finegold M, Grompe M
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• A reproducible and well-tolerated method for 2/3 partial hepatectomy in mice.
  Nature protocols 2008 Mitchell C, Willenbring H
• On the origin of the term "stem cell".
  Cell stem cell 2007 Ramalho-Santos M, Willenbring H
• Myeloid lineage progenitors give rise to vascular endothelium.
  Proceedings of the National Academy of Sciences of the United States of America 2006 Bailey AS, Willenbring H, Jiang S, Anderson DA, Schroeder DA, Wong MH, Grompe M, Fleming WH
• Bone marrow-derived cells fuse with normal and transformed intestinal stem cells.
  Proceedings of the National Academy of Sciences of the United States of America 2006 Rizvi AZ, Swain JR, Davies PS, Bailey AS, Decker AD, Willenbring H, Grompe M, Fleming WH, Wong MH
• Sustained phosphorylation of Bid is a marker for resistance to Fas-induced apoptosis during chronic liver diseases.
  Gastroenterology 2006 Vogel A, Aslan JE, Willenbring H, Klein C, Finegold M, Mount H, Thomas G, Grompe M
• Myeloid Lineage-Restricted Progenitors Contribute to Vascular Endothelium.
  Blood 2005 Alexis S. Bailey, Holger Willenbring, Shuguang Jiang, David A. Schroeder, Daniel A. Anderson, Markus Grompe, Melissa H. Wong, William H. Fleming
• In vivo genetic selection of renal proximal tubules.
  Molecular therapy : the journal of the American Society of Gene Therapy 2005 Held PK, Al-Dhalimy M, Willenbring H, Akkari Y, Jiang S, Torimaru Y, Olson S, Fleming WH, Finegold M, Grompe M
• Therapeutic cell fusion.
  The British journal of surgery 2005 Willenbring H
• Delineating the hepatocyte's hematopoietic fusion partner.
  Cell cycle (Georgetown, Tex.) 2004 Willenbring H, Grompe M
• Myelomonocytic cells are sufficient for therapeutic cell fusion in liver.
  Nature medicine 2004 Willenbring H, Bailey AS, Foster M, Akkari Y, Dorrell C, Olson S, Finegold M, Fleming WH, Grompe M
• Embryonic versus adult stem cell pluripotency: in liver only fusion matters.
  Journal of assisted reproduction and genetics 2003 Willenbring H, Grompe M
• Cell fusion is the principal source of bone-marrow-derived hepatocytes.
  Nature 2003 Wang X, Willenbring H, Akkari Y, Torimaru Y, Foster M, Al-Dhalimy M, Lagasse E, Finegold M, Olson S, Grompe M
• Argininosuccinate lyase (ASL) deficiency: mutation analysis in 27 patients and a completed structure of the human ASL gene.
  Human genetics 2002 Linnebank M, Tschiedel E, Häberle J, Linnebank A, Willenbring H, Kleijer WJ, Koch HG
• Genomic structure and transcript variants of the human methylenetetrahydrofolate reductase gene.
  European journal of human genetics : EJHG 2000 Homberger A, Linnebank M, Winter C, Willenbring H, Marquardt T, Harms E, Koch HG
• Telomerase activity distinguishes between neuroblastomas with good and poor prognosis.
  Annals of oncology : official journal of the European Society for Medical Oncology 1999 Poremba C, Willenbring H, Hero B, Christiansen H, Schäfer KL, Brinkschmidt C, Jürgens H, Böcker W, Dockhorn-Dworniczak B
• Telomerase activity in human proliferative breast lesions.
  International journal of oncology 1998 Poremba C, Böcker W, Willenbring H, Schäfer KL, Otterbach F, Bürger H, Diallo R, Dockhorn-Dworniczak B
• Nonisotopic single strand conformation analysis of the 5 alpha-reductase type 2 gene for the diagnosis of 5 alpha-reductase deficiency.
  The Journal of clinical endocrinology and metabolism 1996 Hiort O, Sinnecker GH, Willenbring H, Lehners A, Zöllner A, Struve D
• Molecular genetic analysis and human chorionic gonadotropin stimulation tests in the diagnosis of prepubertal patients with partial 5 alpha-reductase deficiency.
  European journal of pediatrics 1996 Hiort O, Willenbring H, Albers N, Hecker W, Engert J, Dibbelt L, Sinnecker GH