Ira J. Fox, MD

  • Professor of Surgery and Clinical and Translational Science
  • Graduate Faculty, Cellular and Molecular Pathology Training Program

Administrative Assistant: Tamara Daviston

Dr. Ira Fox is a Professor of Surgery at the University of Pittsburgh School of Medicine, and a member of the Executive Committee of the McGowan Institute for Regenerative Medicine.  Prior to this, Dr. Fox served as Senior Associate Dean for Research and Development at the University of Nebraska College of Medicine as well as the Charles W. McLaughlin Professor of Surgery (and Pathology and Microbiology) at the University of Nebraska Medical Center.

Dr. Fox graduated from Harvard College with a degree in Chemistry and Physics. From there he attended Columbia University, College of Physicians and Surgeons, where he earned his medical degree. He completed post doctorate fellowships first at Harvard Medical School (Immunology Research Fellow) and then at the University of Pittsburgh School of Medicine (Transplant Fellow).

Dr. Fox’s primary research interests involve the study of experimental therapies for liver disease, including liver assist devices, liver cell transplantation, liver stem cells, and in vivo reprogramming of injured cells in cirrhosis. Dr. Fox’s laboratory examines the biologic and immunologic barriers to successful transplantation of primary and xenogeneic hepatocytes in rodents and primates. He has developed a model of acute liver failure that mimics the clinical entity in non-human primates and a model of end-stage liver failure resulting from cirrhosis in rodents. With these models he is able to assess the mechanisms responsible for liver failure in these two entities and studies various strategies for hepatic regeneration.

His laboratory also generates pluripotent stem cells (iPS cells) from normal individuals and patients with various liver diseases, and differentiates these human iPS and embryonic stem cells into liver cells to model diseases such as alpha-1-antitrypin deficiency and familial intrahepatic cholestasis, to study drug metabolism, and to develop source cells for hepatocyte transplantation. He has initiated clinical trials involving extracorporeal liver perfusion to treat patients with acute liver failure, and has demonstrated successful correction of liver-based metabolic deficiencies in newborns and young children by transplantation of isolated liver cells. Several FDA-approved clinical trials of hepatocyte transplantation for treatment of patients with Liver Based Metabolic Disorders, Acute Decompensated Liver Failure, and Phenylketonuria are underway that involve a conditioning regimen that is meant to selectively induce donor cell expansion.

Dr. Fox holds two U.S. investigational new drug patents and has authored over 150 peer reviewed publications as well as 20 book chapters.  He is the co-editor of the book, Cell Transplantation Methods (Artech House, May 2011). He is on the editorial board of Stem Cells, Cell Transplantation, and Cell Medicine, and is an ad hoc reviewer for many journals, including Nature, Nature Biotechnology, Nature Medicine, Nature Cell Biology, Science, Science Translational Medicine, Journal of Clinical Investigation, PNAS, Gastroenterology, and Hepatology.

Professional and Scientific Society Memberships

  • American Association for the Study of Liver Diseases
    • Surgery and Liver Transplantation Committee 2001-2004
  • American College of Surgeons
    • Scientific Program Director, Nebraska Chapter ACS Annual Spring Meeting 1998
  • American Society of Gene Therapy
    • Embryonic Stem Cells and Tissue Engineering Committee 2005-2008
  • American Society of Transplant Surgeons
    • Education Committee 1993-95, 1997-1999
    • Postgraduate Course Committee 1995-1996
    • Cell Transplant Committee 2001-2003
  • American Society of Transplantation
    • Cellular Transplantation Committee 2002-2007
    • Chair 2006-2007
    • Ad hoc AST-NIH Committee 2005-2006
    • Co-Organizer, Seventh Annual AST Winter Symposium, 2003
  • Metropolitan Omaha Medical Society
  • New York Surgical Society
  • Society of Critical Care Medicine
  • Society of University Surgeons
  • Surgical Research Society of Australasia - Honorary Membership
  • Transplantation Society
    • Local Organizing Committee- VI International Small Bowel Transplant Symposium
  • Transplantation Society of Australia and New Zealand
  • Cell Transplant Society
    • Council Member
  • American Surgical Association
  • The Henry Kunkel Society
  • International Society for Stem Cell Research
    • Member, Outstanding Young Investigator Award Committee 2009-2014
    • Member, Membership Committee 2016-Present
  • Tissue Engineering and Regenerative Medicine International Society (TERMIS)
  • International Advisory Board Committee for the 2009 TERMIS World Congress (and the 2009 Seoul Stem Cell Symposium)

Education & Training

  • AB cum laude, Chemistry and Physics, Harvard College, 1972
  • MD, Columbia University, College of Physicians and Surgeons, 1976
  • Internship, Department of Surgery, Columbia Presbyterian Medical Center, 1976-1977
  • Assistant Residency, Department of Surgery, University of California Medical Center, 1977-1979
  • Immunology Research Fellowship, Department of Pathology, Harvard Medical School, 1979-1981
  • Senior/Chief Residency, Deaconess-Harvard Surgical Service, New England Deaconess Hospital, 1981-1983
  • Transplant Fellowship, Department of Surgery, School of Medicine, University of Pittsburgh, 1983-1985

Selected Publications

Nishikawa T, Bell A, Brooks JM, Setoyama K, Melis M, Han B, Fukumitsu K, Handa K,  Tian J, Kaestner KH, Vodovotz Y, Locker J, Soto-Gutierrez A, Fox IJ.  Resetting the transcription network using a single factor reverses liver failure in end-stage cirrhosis.  Journal of Clinical Investigation 2015; 125(4): 1533-44.

Chen Y, Chang C-J, Li Y, Ding J, Atienza K, Wang X, Avsar Y, Tafaleng E, Strom S, Guha C, Bouhassira EE, Fox IJ, Roy-Chowdhury J, Roy-Chowdhury N.  Amelioration of hyperbilirubinemia in Gunn rats after transplantation of human induced pluripotent stem cell-derived hepatocytes. Stem Cell Reports 2015; 5(1): 22-30.

Tafaleng EN, Chakraborty S, Han B, Hale P, Wu W, Soto-Gutierrez A, Feghali-Bostwick CA, Wilson AA, Kotton DN, Nagaya M, Strom SC, Roy-Chowdhury J, Stolz DB, Perlmutter DH, Fox IJ.  Induced pluripotent stem cells model personalized variations in liver disease due to α1-antitrypsin deficiency. Hepatology 2015; 62(1): 147-57.

Sauer V, Tchaikovskaya T, Wang X, Li Y, Zhang W, Tar K, Polgar Z, Ding J, Guha C, Fox IJ, Roy-Chowdhury N,, Roy-Chowdhury J. Human urinary epithelial cells as a source of engraftable hepatocyte-like cells using stem cell technology. Cell Transplantation 2016; 25(12):2221-2243.

Soltys KA, Setoyama K, Tafaleng EN, Soto Gutiérrez A-S, Fong J, Fukumitsu K, Nishikawa T, Nagaya M, Rachel Sada R, Haberman K, Gramignoli R, Dorko K, Tahan V, Dreyzin A, Baskin K, Crowley JJ, Quader MA, Deutsch M, Ashokkumar C, Shneider BL, Squires RH, Ranganathan S, Reyes-Mugica M, Dobrowolski SF, Mazariegos G, Elango R, Stolz DB, Strom SC, Vockley G, Roy-Chowdhury J, Cascalho M, Guha C, Sindhi R, Platt JL, Fox IJ. Host conditioning and rejection monitoring in clinical hepatocyte transplantation. J Hepatology 2017; 66(5):987-1000.

Fukumitsu K, Handa K, Matsubara K, Guzman-Lepe J, Collin de l'Hortet A, Takeishi K, Wang Y, Strauser JC, Wendell S, Tobita K, Shapiro EM, Ye SH, Oertel M,  Stolz DB, Piganelli JD, Wagner WR, Gilbert TW,  Strom SC, Yagi H, Fox IJ, Soto-Gutierrez A. Assembly of a bioengineered liver capable of extended function and regeneration in vivo. Nat Biotech. 2018 (in revision)

Guzman-Lepe J, Cervantes-Alvarez E, Collin de l'Hortet A, Wang Y, Mars WM, Oda Y, Bekki Y, Shimokawa M, Wang H, Yoshizumi Y,  Maehara Y, Bell A, Fox IJ, Takeishi K, Soto-Gutierrez A. Liver-Enriched Transcription Factors Expression Relates to Chronic Hepatic Failure in Humans. Hepatology Comm 2018 2(5): 582-594.

Collin de l'Hortet A, Takeishi K, Guzman-Lepe J, Morita K, Achreja A, Popovic B, Wang Y, Handa K, Mittal A, Meurs N, Zhu Z, Weinberg F, Salomon M, Fox IJ, Deng CX, Nagrath D, Soto-Gutierrez A. Generation of Human Fatty Livers Using Custom-engineered Induced Pluripotent Stem Cells with Modifiable SIRT1 metabolism. Cell Metab. 2019 Aug 6;30(2):385-401.e9. doi: 10.1016/j.cmet.2019.06.017. PMID: 31390551

Florentino RM, Fraunhoffer NA, Morita K, Takeishi K, Ostrowska A, Achreja A, Animasahun O, Haep N, Arazov S, Agarwal N, Collin de l’Hortet A, Guzman-Lepe J, Tafaleng EN, Mukherjee A, Troy K, Banerjee S, Paranjpe S, Michalopoulos GK, Bell A, Nagrath D, Hainer SJ, Fox IJ, Soto-Gutierrez A. Cellular location of HNF4α is linked with terminal liver failure in humans. Hepatology Communications 2020 May 31; 4(6) DOI:10.1002/hep4.1505 

Kazuki Takeishi K, Alexandra Collin de l’Hortet A, Wang Y, Handa K, Guzman-Lepe J, Matsubara K,  Morita K, Jang S, Haep N, Florentino RM, Yuan F, Fukumitsu K, Tobita K, Sun W, Franks J, Delgado ER, Shapiro EM, Fraunhoffer NA, Duncan AW, Yagi H, Mashimo T, Fox IJ, Soto-Gutierrez A. Assembly and Function of a Bioengineered Human Liver for Transplantation Generated Solely from Induced Pluripotent Stem Cells. Cell Reports 2020 (in press).

Research Grants

2018-2023, PI NIH RO1 “Hepatocyte Transplantation for Liver Based Metabolic Disease, RO1 DK117916 (5yr) Total Direct Costs $3,065,472; (Year 1) $616,712.

2019-2024, PI (Project 3), NIH PO1, “New therapies for liver fibrosis and hyperproliferation in alpha1-AT deficiency” (Perlmutter, PI), Project 3:  “Models of AT deficiency using Human Hepatocytes”. PO1 DK096990, Total Direct Costs (Project 3 (5yr) $2,000,000; (Year 1) $400,000. SS Score 29