Ira J. Fox, MD, Professor of Surgery
University of Pittsburgh School of Medicine
Director, Center for Innovative Regenerative Therapies
Children's Hospital of Pittsburgh of UPMC
and McGowan Institute for Regenerative Medicine
MD, Columbia University College of Physicians and Surgeons, 1976
Email: foxi@upmc.edu
Research Interest:
Dr. Fox's research interests involve the bench-to-bedside study of experimental therapies for liver disease, including liver assist devices, liver cell transplantation, and liver stem cells. His laboratory examines the biologic and immunologic barriers to successful transplantation of primary and xenogeneic hepatocytes, as well as conditionally-immortalized rodent and human hepatocytes. In order to accomplish this goal, his laboratory develops animal models that faithfully mimic human liver disease in rodents and non-human primates. His laboratory also studies differentiation of mouse and human embryonic stem (ES cells) and inducible pluripotent stem (iPS cells) cells into liver cells. The laboratory uses such cells to repopulate the livers of immune-deficient mice to model and study human liver diseases such as human alpha-1-antitrypsin deficiency and alcoholic liver disease. Based on laboratory studies, he and his associates have initiated clinical trials involving extracorporeal xenogeneic liver perfusion to treat patients with acute liver failure, and have demonstrated successful correction of liver-based metabolic deficiencies in newborns and young children by transplantation of isolated liver cells.
Representative Publication
Schumacher IK, Okamoto T, Kim BH, Chowdhury NR, Chowdhury JR, Fox IJ: Transplantation of conditionally immortalized hepatocytes to treat hepatic encephalopathy. Hepatology 1996;24(2):337-43.
Fox IJ, Roy Chowdhury J, Kaufman SS, Goertzen TC, Roy Chowdhury N, Warkentin PI, Dorko K, Sauter B, Strom SC: Treatment of Crigler-Najjar syndrome type I with hepatocyte transplantation. N Engl J Med 1998;338(20):1422-1426.
Horslen SP, Hammel JM, Fristoe LW, Kangas JA, Collier DS, Sudan DL, Langnas AN, Dixon RS, Shaw BW, Fox IJ. Extracorporeal liver perfusion with human and pig livers for acute liver failure. Transplantation 2000;70(10):1472-1478.
Cai J, Ito M, Westerman KA, Kobayashi N, Laboulch P, Fox IJ. Construction of a transplantable hepatocyte cell line: reversal of hepatocyte immortalization by site-specific excision of the SV40 T antigen. J Hepatology 2000;33(5):701-708.
Kobayashi N, Ito M, Nakamura J, Cai J, Gao C, Hammel JM, Fox IJ. Hepatocyte transplantation in rats with decompensated liver cirrhosis. Hepatology 2000;31(4):851-857.
Kobayashi N, Fujiwara T, Westerman KA, Inoue Y, Sakaguchi M, Noguchi H, Miyazaki M, Cai J, Tanaka N, Fox IJ, Leboulch P. Prevention of acute liver failure in rats with reversibly immortalized human hepatocytes. Science 2000;287(5456):1258-1262.
Cai J, Ito M, Nagata H, Westerman KA, LaFleur D, Roy Chowdhury J, Leboulch P, Fox IJ. Treatment of liver failure in rats with end-stage cirrhosis by transplantation of conditionally immortalized hepatocytes. Hepatology 2002;36(2):386-394.
Ito M, Nagata H, Cai J, Edge A, Platt JL, Fox IJ. Treatment of cirrhosis and liver failure by hepatocyte xenotransplantation. Gastroenterology 2003;124(2):422-431.
Horslen SP, McCowan TC, Guertzen TC, Warkentin PI, Strom SC, Fox IJ. Isolated hepatocyte transplantation in an infant with a severe urea cycle disorder. Pediatrics 2003;111(6):1262-1267.
Soto-Gutierrez A, Kobayashi N, Rivas-Carrillo JD, Navarro-Alvarez, N Zhao D, Okitsu T, Noguchi H, Matsumoto S, Chen Y, Tanaka K, Narushima M, Miki A, Ueda T, Stolz DB, Lebowski J, Jun H-S, Tanaka N, Yoon J-W. Fox IJ. Reversal of liver failure in mice using an implanted liver assist device containing ES cell-derived hepatocytes. Nature Biotechnology 2006;24(11):1412-1419.
Nagata H, Nishitai R, Shirota C, Zhang J, Koch CA, Cai J, Awaad M, Schuurman H-J, Christians U, Abe M, Baranowska-Kortylewicz J, Platt JL, Fox IJ. Prolonged survival of porcine hepatocytes in cynomolgus monkeys. Gastroenterology 2007;32:321-329.
Ito M, Ito R, Yoshihara D, Ikeno M, Kamiya M, Suzuki N, Horiguchi A, Nagata H, Yamamoto T, Kobayashi N, Fox IJ, Okazaki T, Miyakawa S. Immortalized hepatocytes using a human artificial chromosome. Cell Transplantation 2008;17:165-171.
Hyun I, Lindvall O, Ahrlund-Richter L, Cattaneo E, Cavazzana-Calvo M, Cossu G, De Luca M, Fox IJ, Gerstle C, Goldstein RA, Hermerén G, High KA, Kim HO, Lee HP, Levy-Lahad E, Li L, Lo B, Marshak DR, McNab A, Munsie M, Nakauchi H, Rao M, Rooke HM, Valles CS, Srivastava A, Sugarman J, Taylor PL, Veiga A, Wong AL, Zoloth L, Daley GQ. New ISSCR guidelines underscore major principles for responsible translational stem cell research. Cell Stem Cell 2008;3(6):607-609
Yamanouchi K, Zhou H, Roy-Chowdhury N, Mancuso F, Liu L, Yamamoto T, Yannam GR, Solberg TD, Adelson AB, Platt JL, Fox IJ, Roy-Chowdhury J, Guha C. Hepatic irradiation augments engraftment of donor cells following hepatocyte transplantation. Hepatology 2009;49(1):258-267.
Basma H, Alejandro Soto-Gutierrez A, Yannam GR, Liu L, Ito R, Ellis E, Carson SD, Sato S, Muirhead D, Navarro-Alvarez N, Wong R, Mercer DF, Miller JD, Strom SC, Kobayashi N, Fox IJ. Differentiation and transplantation of human embryonic stem cell-derived hepatocytes. Gastroenterology, in press (Epub ahead of publication).
