Researcher

Title

• Chief, Division of Gastroenterology, Hepatology and Nutrition, CHU Sainte-Justine, University of Montreal, 2009.
• Professor, Department of Microbiology and Immunology, University of Montreal, 2005.
• Co-Director, Intercultural Pediatrics Unit (Medical Anthropology), CHU Sainte-Justine, University of Montreal, 2001.
• Professor, Division of Gastroenterology, Hepatology and Nutrition, CHU Sainte-Justine, University of Montreal, 1999.
• Professor, Department of Pediatrics, University of Montreal, 1999.
• Director, Hepatic Transplantation Program, CHU Sainte-Justine, University of Montreal, 1995.

• Postdoctorate, Department of Cell Biology, New York University, 1982-1985.
• Postdoctoral training, Liver Diseases Unit, Hôpital de Bicêtre, Université de Paris, 1972-1982.
• Residence in Pediatrics, Children’s Hospital, Buenos Aires, 1975-1978.
• MD, University of Buenos Aires, 1974.

As the liver is constantly exposed to food antigens and intestinal flora products, it deploys immune tolerance mechanisms while maintaining its ability to respond efficiently to infection. In certain pathologies such as autoimmune hepatitis, this immune tolerance is disrupted. And, conversely, in certain chronic viral infections such as hepatitis B and C, this tolerance ability may be harmful. Our laboratory studies hepatic immune tolerance using murine models of autoimmune hepatitis and hepatic inflammation caused by viral infection. Currently our work focuses on the understanding of immunological mechanisms that underlie this tolerance and rupture. In the long run, we aim to develop precise immunotherapies that target mechanisms of hepatic immune homeostasis, which will allow us to reconstitute immune tolerance or the induction of an effective immune response in patients with hepatic autoimmune diseases or chronic infections with hepatitis B and C.

Significant Contributions

• Study of viral hepatitis in immunosuppressed patients (study in progress).
• Development of autoimmune hepatitis animal models (J Immunol 2002, Hepatology 2004). These models allow us to study the pathogenesis of the disease and test new therapies. The model has thus far allowed us to describe the influence of non-HCM genes (J Autoimmunity, 2006) and find the mechanism behind the influence of age and sex in the development of the disease (Hepatology, 2010).
• Development of new diagnostic tests (two of which have been patented) (J Immuno Methods 2002). Contribution to a better understanding of the pathogenesis of autoimmune hepatitis.
• Identification of formiminotransferase cyclodeaminase as an antigen recognized by anti-LC1 antibodies in patients with type 2 autoimmune hepatitis (Gastroenterology 1999).
• Identification of the cytochrome P450 2D6 as the antigen recognized by liver-kidney microsomal autoantibodies type 1 from patients with AIH type 2. Characerization of the antigen sites (J Exp Med 1985, J Exp Med 1988, Gastroenterology 1988).
• Description of patients with AIH type 2 and chronic hepatitis C with in sera LKM1 antibodies (Gastroenterology 1993, Eur J Immunology 1993, JPGN 1999) and anti-LC1 antibodies (J Autoimmunity 2004). Identification of their underlying mechanisms (Hepatology 2005).
• Characterization of antigenic sites of the asialoglycoprotein receptor recognized by autoantibodies in sera of patients with AIH (Clin Exp Immunol 1998, Eur J Pediatr 2000).
• Intracellular mechanisms of retention and degradation of 1-anti-trypsine PZ. This work contributed to the understanding of cell toxicity in 1 anti-trypsine deficiency associated with the Z mutation (FEBS Letters 1999, Eur J Biochem 1993).
• Vitamin A and E deficiencies: Diagnosis and treatment in children with cholestasis. Role of vitamin E in the development of neurological diseases. Our work contributed to an improvement in the follow-up of children with chronic cholestasis. These children are currently treated systematically with vitamin A and E (Hepatology 1983, Hepatology 1985, JPGN 1984, J Pediatr 1985).
• Long-term culture of rat and human hepatocytes. This work showed that hepatocytes in primary culture can stay in a differentiate status for several months and described some of the condition required (Exp Cell Res 1990, Exp Cell Res 1992, Biol Cell 1994).

Career Summary

Professional Experience

• Director, Department of Pediatrics, University of Montreal, 2001-2006.
• Chief, Department of Pediatrics, CHU Sainte-Justine, 2001-2006.