A propos - Curriculum Vitae

 

CHRISTIAN BRECHOT

DATE/PLACE OF BIRTH: JULY 23, 1952, PARIS, FRANCE

POSITION TITLE:                   

Vice-President for medical and Scientific Affairs
Mérieux Alliance  

ADDRESS:  

35 Boulevard Pasteur
75015 Paris
 
Cell phone: + 33 6 08 97 98 99

Email: christianbrechot2005@yahoo.fr

                                

EDUCATION                                YEARS           DEGREE  

Certificate in General Immunology,         1980            M.D., PhD
Pasteur Institute, ParisM.D.,

Medical thesis: hepatitis                            1983
B virus infection and liver disease

Ph.D. in Biochemistry: Hepatitis                1985
B virus and primary liver cancer

Research fellowships

1979-1985       Research training in molecular biology. Pasteur Institute (Professor Tiollais laboratory), Paris

Academic appointments

1989-2001       Professor of cell biology, Necker School of Medicine - University Paris V

1992-              Member of “Institut Universitaire de France”, Paris

1993-2001 Director, Inserm research unit 370, Necker School of Medicine, Paris.

1990-1998 Head of Hybridotest laboratory, Pasteur Institute, Paris

1998-2001       Head of the National Reference Center on the molecular epidemiology of viral hepatitis, Pasteur Institute and Inserm U370, Paris

2001-2007      Director General of the French institute for health and medical research  (Inserm)

2002-2006       President of the French National Consortium for Research in Genomics (CNRG)

From January 2008: Vice-Président for Medical and Scientific Affairs of MERIEUX- ALLIANCE     Biomedical Company

Hospital appointment

  • 1997-2001 Head, Liver Unit, Necker Hospital, Paris.

Societies

  • European Association for the Study of the Liver (Secretary 1993-1997), French Association for the Study of the Liver (AFEF), American Association for the Study of Liver Diseases (AASLD), European Association for Virological Diagnosis

Awards and honors

  • 1982    « Biotrol » Award. Colloque Biologie et Prospective, Pont-à-Mousson
  • 1982    The « Fondation pour la Recherche Médicale » Award for clinical investigation
  • 1983    « Abott » Award for research on viral Hepatitis
  • 1985    The « Ligue Française contre le cancer » Paris Award, for research on liver cancer and hepatitis B virus
  • 1987    « APMS » Award, for research on prevention of transmissible diseases
  • 1987    The French Medical Society « René Fauvert » Award
  • 1986    The French Academy of Medicine Award,
  • 2000    The « Fondation de France » Jean Valade Award
  • 2002    Associate Professor, Pasteur Institute, Paris
  • 2002    Knight of the French national Order of Merit
  • 2005    Knight of the French national Legion of Honor
  • 2005    Honorary Professor of Shanghaï Jiao Tong University, 2005
  • 2006    Honory Degree “Honoris Causa Doctor of Science”, Glasgow University

Major committees assignments

  • 1990-1994      Inserm Specialized Scientific Commission 3
  • 1992-1996       Coordinator of a European Union Concerted Action on the molecular analysis of primary hepatocellular carcinoma in different geographical areas in Europe
  • 1993-1996      Scientific Committee “Agence Française du Sang”
  • 1988-2001 Scientific Committee of the «Association pour la Recherche sur le Cancer»
  • 1988-2001 WHO study coordinator for the standardization of PCR in the diagnosis of HIV infections
  • 1998-2001      Inserm Specialized Scientific Commission 8
  • 2002-              Member of Paris City’s Scientific Committee

Overview of the Main scientific and administrative achievements

Christian Bréchot graduated in medicine in Paris and presented his medical thesis in 1983. He holds MD Ph.D degrees, and beginning in 1981 he studied molecular biology, virology, and cellular biology at the laboratory of Pierre Tiollais at the Pasteur Institute, and at the Necker Faculty of Medicine; he obtained his Ph.D in biochemistry from the University of Paris VII in 1985. In 1989 he became full professor of Cell Biology and Hepatology, and in 1997 he was appointed head of the clinical department of liver diseases at the Necker-Enfants Malades Hospital. He has been in charge of a research unit at the Necker Faculty of Medicine, jointly supported by Inserm (the French national biomedical research agency), Paris Descartes University, and the Pasteur Institute; he was also head of the National Reference Centre on viral hepatitis from 1998 to 2001.

 

Christian Bréchot’s research has been mainly focussed on viral hepatitis: hepatitis B (HBV) and C (HCV), particularly with regard to their role in liver cancer (Hepatocellular carcinoma: HCC) and to the molecular mechanisms that drive liver regeneration and cancer (in particular, cell cycle deregulation). These topics have been investigated by combining basic and clinical research in molecular virology and cell biology. He has contributed to the understanding of the mechanisms that generate liver carcinogenesis in HBV- and HCV-chronically infected patients (notably the impact of HBV DNA integration and the interactions between HCV proteins and major cell signalling pathways, such as interferon and TGF-b); his group has also contributed to explaining several aspects of cell cycle regulation, in particular, through the identification of human cyclin A at the site of HBV genome insertion in an HCC. Concurrently, he has headed several projects that have led to the design of a novel diagnostic test for the detection and quantification of HBV DNA in serum. He has performed studies that investigate the clinical impact of HCV genetic variability, and his group has led several clinical studies that have contributed to demonstrating the efficacy of interferon-ribavirin combination for treating HCV infections; he has also conducted initial studies that investigate the efficacy of active specific immunotherapy against HBV in chronically infected subjects. In addition, his group has developed novel approaches based on gene therapy for treating liver cancer.

 

Since 2001, he has acted as General Director of Inserm, while maintaining research activities with the creation of a novel research unit (directed by Professor Didier Samuel) in the Hepato-Biliary Centre in Villejuif, a leading European centre for liver transplantation near Paris; his group’s present activities have been focusing on the identification of a novel mitogenic and anti-apoptotic factor (HIP/PAP/Reg) for liver cells with potential clinical relevance in stimulating liver regeneration. In addition, his group is investigating the expression patterns of the sodium iodide symporter (NIS) in normal and malignant biliary cells, and the clinical potential of these findings for the use of 131 Iodide in the treatment of cholangiocarcinomas; with this in view, they have demonstrated both the potential of NIS cDNA-based gene therapy to transduce Hepatocarcinoma tumor cells and the use of 131 Iodide to treat HCC’s. His group is also investigating the impact of HCV genetic variability in HCC development, presently focusing on the interplay between the HCV core protein and TGF-b signalling. Finally, they have also used laser-based microdissection of liver sections to detect HCV RNA and to investigate HCV quasi-species as well for liver proteomic analysis.

 

From 2001 to 2007, Christian Bréchot has acted as General Director of Inserm, the French National Agency for biomedical research. Thirteen thousand people are employed within its 300 research units and 25 research centres.

 

His various actions have led to a significant reorganization of the classical scheme of French research: he has set up new career tracks for young and seniors scientists, thus stimulating the emergence of new talents, providing earlier access to scientific autonomy, significantly reinforcing the financial attractiveness of career tracks, as well as the links between basic and clinical research, teaching, industry, and public health. He has proposed novel tools to clinicians to encourage training and research activity. In addition, his actions have led to a general reorganization of infrastructures and a reactivation of research units through the creation of several research centres. He has significantly reinforced Inserm’s European and international involvement, including the participation of Inserm in European and international programs as well as the establishment of Inserm’s units abroad (Heidelberg, Glasgow, Montreal, Shanghai, etc.) Finally, he has notably fostered the transfer of technology and valuation activities through the specific training of scientists, the reinforcement of programs for identification and development of “early projects”, and the creation of a private subsidiary (Inserm Transfert), which now oversees all valuation activities.

 

From January 2008, he will join Mérieux Alliance to become vice-president for international medical research and development. His task will be to define an overall scientific and clinical vision for the different components of this holding company (two companies in France, two in the US and one in India); also Mérieux Alliance has for many years demonstrated a major implication in promoting sustainable research development in developing countries.

  

SCIENTIFIC ACHIEVMENT

>>>  Basic Research

  • Contribution to the understanding of Hepatitis B-and Hepatitis C -related Liver Carcinogenesis.
  • Understanding hepatocyte cell cycle regulation and its dysregulation upon HBV and HCV infections.
  • Investigating interference between HBV and HCV proteins (HBx and HCV core) with TGF-beta-and calcium dependent-signaling, investigating HCC tumor and non tumor derived natural HCV mutants.
  • Unraveling mechanisms regulating liver regeneration: identification of a novel mitogenic and anti-apoptotic factor: Hepatocellular carcinoma - Intestine- Pancreas (HIP/PAP).

>>>   Setting up novel diagnostic tests

  • HBV/DNA as the most reliable marker for HBV multiplication detection.
  • Demonstration of the clinical, anatomo-pathological and biological implication of HBV and HCV genetic variability (HCV genotypes and quasi species).
  • Cyclin A as an important marker for tumor cell proliferation.
  • Isolation of circulating metastatic cells with the Isolation upon Size of Epithelial Tumor Cells (ISET) technology .
  • Novel therapy (HIP/PAP mitogenic factor) for treating fulminant hepatitis
  • Gene therapy (NIS) for liver cancer treatment

>>> Therapeutical contributions

  • Overall management of HBV and HCV chronically infected patients, focussing in particular on Interferon / Ribavirin therapy for chronic hepatitis C.
  • First protocol of therapeutic vaccination against chronic HBV infection using a DNA vaccine.
  • Recent demonstration of the potential of the HIP/HAP protein for treating acute liver failure and stimulating liver regeneration.
  • Gene therapy for liver cancer using a Sodium Iodide Symporter as target gene.

Overall these studies have been characterised by a close association between basic and clinical research. They have led to the creation of two biotechnology companies : Metagenex and ALFACT Innovation.

Administrative and Management Achievements

General Director of the Institut National de la Santé et de la Recherche Médicale (Inserm) from 2001. Inserm is the French National Agency for biomedical research. Thirteen thousand peoples are working in its 360 research units.

The different actions have led to a significant reorganization of the classical scheme of French research :

  • New career tracts for young and seniors scientists.
  • Stimulation of new talent emergence, earlier access to scientific autonomy, significant reinforcement of financial attractivity of the career tracts and of the links between basic and clinical research, teaching, industry, public health.
  • Stimulation of training and participation of clinicians to research.
  • General reorganization of the infrastructures and dynamization of the research units. Creation of several research centres.
  • Significant reinforcement of the European and International implication of Inserm, including participation to European and International programs as well as establishment of Inserm Units abroad (Heidelberg, Glasgow, Montreal, Shanghaï, etc).
  • Reinforcement of technology transfer and valorisation activities : training of scientists, reinforcement of programs for identification and development of “early projects”, creation of a private subsidiary (Inserm Transfert) which is now in charge with the overall valorisation activities.

  

Main publications

Christian Bréchot has been the member of numerous scientific committees and societies and has received prestigious awards. Overall, he is the author of over 350 articles published in medical and scientific journals, of which 85 with a citation index exceeding 50 and a factor “H” of 67 (HIRSCH, J.E. (2005) http://arxiv.org/abs/physics/0508025. Nature (2005) vol. 436 : 900).  He also ranked 4th in the ISI survey on the most cited authors concerning hepatitis C.

In addition, his research activities have led him to obtain x patents and to contribute to the creation of two biotech companies: Metagenex and ALFACT Innovation.

Some representative papers:

  • 1. BRECHOT, C., POURCEL, C., LOUISE, A., RAIN B., and TIOLLAIS P. Presence of integrated hepatitis B virus DNA sequences in cellular DNA of human hepatocellular carcinoma. Nature, 1980, 286, 533-535.
  • 2. BRECHOT, C., HADCHOUEL, M., DEGOS, F. LUGASSY, C., THIERS, V., ZAFRANI, S., FRANCO, D., BISMUTH, H., TREPO, C., BENHAMOU, J.P., WANDS, J., ISSELBACHER, K., TIOLLAIS, P., and BERTHELOT, P. Hepatitis B virus DNA in patients with chronic liver disease and negative tests for hepatitis B surface antigen. N. Engl. J. Med., 1985, 312, 270- 276.
  • 3. WANG, J., CHENIVESSE, X., HEINGLEIN, B., and BRECHOT, C. Hepatitis B virus integration in a cyclin A gene in hepatocellular carcinoma. Nature, 1990, 343, 557-557.
  • 4. MURPHY, M., STINNAKRE, M.G., SENAMAUD-BEAUFORT, C., SWEENEY, C., KUBELKA, M., CARRINGTON, M., BRECHOT, C., and SOBCZAK-THEPOT, J. Delayed early embryonic lethality following disruption of the murine cyclin A2 gene. Nature Genetics. 1997, 15: 83-86.
  • 5. BARBA, G., HARPER, F., HARADA, T., KOHARA, M., GOULINET, S., MATSUURA, Y., EDER, G., SCHAFF, Z.S., CHAPMAN, M.J., MIYAMURA, T., and BRECHOT, C. Hepatitis C virus core protein shows an exclusively cytoplasmic localization and associates to cellular lipid storage droplets. The Proceeding National Academy of Sciences USA. 1997, 94: 1200-1205.
  • 6. SOUSSAN, P., GARREAU, F., ZYLBERBERG, H., FERRAY, C., BRECHOT, C., and KREMSDORF, D. In vivo expression of a new hepatitis B virus protein encoded by a spliced RNA. Journal of Clinical Investigation. 2000. 105(1): 55-60.
  • 7. FONTAINE, H., CHAIX, M-L., LAGNEAU, J-L., BRECHOT, C., POL, S and a French multicentric study group. Recovery from chronic hepatitis C in long-term responders to ribavirin plus interferon-alpha. Lancet, 2000; 356: 41.
  • 8. GORDIEN, E., ROSMORDUC, O., PELTEKIAN, C., GARREAU, F., BRECHOT, C., and KREMSDORF, D. Inhibition of hepatitis B virus replication by the interferon-inducible MxA protein. Journal of Virology, 2001; 75:2684.
  • 9. PERLEMUTER, G., SABILE, A., LETTERON, P., VONA, G., TOPILCO, A., SAMSON-BOUMA, M.E., CHRETIEN, Y., PESSAYRE, D., KOIKE, K., CHAPMAN, J., BARBA, G., BRECHOT, C. Hepatitis C virus core protein inhibits microsomal triglyceride transfer protein activity and very low density lipoprotein secretion:a model of viral-related steatosis. FASEB Journal. 2002, 16:185-194.
  • 10. TRALHAO, G., ROUDIE, J., MOROSAN, S., GIANNINI, C., TU, H., GOULENOK, C., CARNOT, F., ZAVALA, F., JOULIN, V., KREMSDORF, D., BRECHOT, C. Paracrine in vivo inhibitory effects of hepatitis B virus X (HBx) protein on liver cell proliferation:a new mechanism of HBx-related pathogenesis. Proc. Natl Acad. Sci. (USA) 2002, 99:6991-6996
  • 11. SIMON MT, PAULOIN A, NORMAND G, LIEU HT, MOULY H, PIVERT G, CARNOT F, TRALHAO JG, BRECHOT C. HIP/HAP stimulates liver generation after partial hepatectomy and combines mitogenic and anti-apoptotic functions through the PKA signaling pathway. FASEB J. 2003, 17(11):1141-50.
  • 12. FAIVRE J, CLERC J, GEROLAMI R, HERVE J, LONGUET M, LIU B, ROUX J, MOAL F, PERRICAUDET M, BRECHOT C. Long-term radioiodine retention and regression of liver cancer after Sodium Iodide Symporter gene transfer in Wistar rats. Cancer Research. 2004. Nov 1;64 (21): 8045.51.
  • 13. GIRARD S, VOSSMAN E, MISEK D E, PODEVIN P, HANASH S, BRECHOT C, BERETTA L. HCV NS5A-regulated gene expression and signaling revealed by microarray and comparative promoter analyses. Hepatology. 2004. Oct; 40(3) 708-18.
  • 14. MANCINI-BOURGINE M, FONTAINE H, SCOTT-ALGARA D, POL S, BRECHOT C, MICHEL ML. Induction or expansion of T-cell responses by a hepatitis B DNA vaccine administered to chronic HBV carriers. Hepatology, vol 40 (4) 874-882.
  • 15. ANDRE P., PERLEMUTER G., BUDKOWSKA A., BRECHOT C., LOTTEAU V. Hepatitis C virus particles and lipoprotein metabolism. Semin Liver Dis. 2005, Feb 25,(1):93-104.
  • 16. MURAKAMI Y., SAIGO K., TAKASHIMA H, MINAMI M., OKANOUE T., BRECHOT C., PATERLINI-BRECHOT P. Large scaled analysis of hepatitis B virus (HBV) DNA integration in HBV related hepatocellular carcinomas. Gut, 2005 Aug,54(8):1162-8.
  • 17. PAVIO N, BOUCREUX D, BATTAGLIA S, ARNULF B, SOBESKY R, HERMINE O, BRECHOT C. Hepatitis C virus core variants isolated from liver tumor but not from adjacent non tumor interact with Smad3 and inhibit the TGF-beta signaling. Oncogene. 2005, Sept 8;24(40):6119-32.
  • 18. LIEU HT., BATTEUX F., SIMON MT., CORTES A., NICCO C., ZAVALA F., PAULOIN A., TRALHAO JG., SOUBRANE O., WEILL B., BRECHOT C., CHRISTA L. HIP/PAP accelerates liver regeneration and protects against acetaminophen injury in mice. Hepatology, 2005 Sep, 42(3):618-26.
  • 19. HAEFFNER-CAVAILLON N., GRAILLOT-GAK C., BRECHOT C. Automated grading of research performance clearly fails to measure up. Nature, 2005, Dec 1, 438(7068):559.
  • 20. LIEU HT, Simon HT, NGUYEN-KHOA T, KEBEDE M, CORTES A, TEBARr L, SMITH AJ, BAYNE R, HUNT SP, BRECHOT C, CHRISTA L. Reg2 inactivation increases sensitivity to Fas hepatotoxicity and delays liver regeneration post-hapatectomy in mice. Hepatology. 2006 Dec;44(6):1452-64.

•21. LIU B, HERVE J, BIOULAC-SAGE P, VALOGNE Y, ROUX J, YILMAZ F, BOISGARD R, GUETTIER C, CALES P, TAVITIAN B, SAMUEL D, CLERC J, BRECHOT C and FAIVRE J; Sodium iodide symporter is expressed at the preneoplastic stages of liver carcinogenesis and in human cholangiocarcinoma. Gastroenterology. 2007 Apr;132(4):1495-503. Epub 2007 Jan 26.

22. HERVE J, SA CUNHA A, LIU B, VALOGNE Y, LONGUET M, BOISGARD R, BREGERIE O, ROUX J, GUETTIER C, CALES C, TAVITIAN B, SAMUEL D, CLERC C, BRECHOT C and FAIVRE J. Internal radiotherapy of liver cancer with rat Hepatocarcinoma-Intestine-Pancreas gene as a liver tumor-specific promoter.