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© Research
Member: Honorary President of the Departement - Alumni

Moshe Yaniv

Alumni
Scientific Fields
Diseases
Organisms
Applications
Technique

About

            During his PhD thesis with François Gros, Moshe Yaniv studied the genetic control of protein synthesis in E. coli. He isolated temperature sensitive mutants for growth and showed that they occur in several aminoacyl-tRNA synthetases. The second part of his thesis involved the purification of several tRNA and the determination of their sequence in the laboratory of Fred Sanger in Cambridge. In collaboration with A. Favre he showed that the 4-thioU residue of the tRNA could be specifically cross-linked to a non- adjacent C residue. With this information in hand together with J. Ninio they proposed a tri-dimensional model of tRNA that was not far from the final structure established later by X ray crystallography. During his postdoctoral stay in Paul Berg’s laboratory in Stanford he produced the first evidence that the anticodon of tRNA is required for its specific recognition by the cognate aminoacyl-tRNA synthetase.

            Following his return to France he started a group studying the structure of Polyoma and SV40 mini-chromosomes. They discovered the nucleosome free region in these chromosomes and showed that such sequences are linked to enhancer function. Together with D. Blangy his group analyzed the sequence of Polyoma mutants that overcame the growth restriction of the virus in pluripotent embryonic cells and showed that they involve sequence rearrangements in the enhancer. This was the first demonstration that small sequence changes in enhancers can change the cell type specificity of gene expression. Following the replication of the viral mini-chromosomes they produced the first evidence showing that both parental histones and the newly synthesized histones associate with newly replicated DNA setting up the principles for transmission of epigenetic information.

            In collaboration with G. Orth, Yaniv and colleagues cloned, sequenced and functionally characterized the first human papillomavirus genome. These were crucial insights that led to the later identification, by others, of genital papillomaviruses associated with cervical cancer. They discovered that the viral E2 protein can act both as a transcription activator and repressor depending on the position of binding sites on the viral DNA.

Developing methods to detect and characterize eukaryotic transcription factors interacting with viral or cellular transcription control elements, they adapted the gel shift assays of DNA- proteins complexes that were previously used in bacteria and drosophila to mouse or human cell extracts. With this approach his group was among the first to isolate and analyze the AP1 transcription factor (an heterodimer between Jun and Fos proteins), and to dissect its role in both transcription and replication of viral DNA. Together with R. Bravo they produced the first evidence that c-Jun is mediating the response to growth factors.

            Moving on from viruses to study the elements in the genome that direct cell type specific gene expression and to investigate their potential role in development, Yaniv’s group collaborated with the laboratory of M. Weiss to map the sequence elements that control liver specific gene expression . This was followed by the purification and cloning of two key transcription factors, Hepatic Nuclear Factor 1a & b (HNF1a, b). Two highly divergent homeobox containg proteins that constitute a distinct mini family among homeobox genes. They produced HNF1a, b deficient mice as well as conditional inactivation that unravelled the key roles of these homeoproteins in directing liver, kidney and pancreas organogenesis and in diseases including phenylketonuria, familial type II diabetes and polycystic kidney disease in humans.

            Coming back to chromatin, his group cloned the Brm helicase gene from humans, a major component of the human SWI/SNF or BAF chromatin remodelling complex and showed that it is important for the transcriptional activation of hormone responsive genes among others. Their studies also revealed a key role for the Brm helicase in growth control and suggested that the SWI/SNF complex may be considered as a candidate tumour suppressor complex. This was directly confirmed by the finding of O. Delattre and his group at the Curie Institute, who demonstrated that bi-allelic mutations or deletions of the SNF5/INI1 gene, another subunit of the complex that they cloned in collaboration with C. Sardet, is found in the quasi totality of infants with rhabdoid brain or kidney tumours. Identical tumours appeared in SNF5+/- mice that they generated. These mice served to unravel the cellular defects that occur in these tumours. Since then, exome sequencing revealed that mutations in the different subunits of the SWI/SNF complex occur in close to 40% of human tumours.

            These studies were made possible by the contributions of many students, postdoctoral fellows and permanent members of the unit whose names are mentioned in the publication list.

CV

Education
1956-1961               M.A. Chemistry, Hebrew University, Jerusalem
1964-1969               Ph.D in Molecular Biology, Paris University (with F. Gros)

Professional experience
1969-1972        Jane Coffin Childs Memorial Fund Postdoctoral fellow, Department of Biochemistry,   Stanford University,  School of  Medicine (with P. Berg)
1972-1981        Chargé et Maître de Recherche, CNRS, Institut Pasteur
1982-2005        Directeur de Recherche, CNRS
2006-                  Directeur de Recherche Emerite, CNRS
1986-2005        Professor, Institut Pasteur 
2006-                  Emeritus Professor, Institut Pasteur                                                                                                                                     1975-2001        Head of Tumor Virus Unit, Institut Pasteur
2002-2005        Head of Gene Expression and Disease Unit, Institut Pasteur 
1986-1988        Chairman, Department of Molecular Biology, Institut Pasteur 
1992-1994        Chairman, Department of Biotechnology, Institut Pasteur                                                                                        2015-                  Honorary President, Department of Developmentam and Stem Cell Biology

Scientific expertise: Regulation of gene expression, signal transduction, genome organization, chromatin and epigenetics, viruses and cancer, mouse models of human cancer, development and organogenesis, type II diabetes

Honors
1978                         Member, European Molecular Biology Organization (EMBO)
1983                         Rosen Prize for Cancer Research, Foundation for Medical Research
1992                         Member, Academia Europaea
1995                         Member, French Academy of Sciences
1995                         Charles Léopold Mayer Prize, French Academy of Sciences
1999                         Chevalier dans l’Ordre de la Légion d’Honneur
2001                         Foreign Honorary Member, American Academy of Arts and Sciences
2001, 2003             Vallee Foundation Visiting Professor, Harvard Medical School
2006                          Mitjavile Prize for Cancer Research, French Academy of Medicine 
2008                          Member, European Academy of Cancer Sciences
2009, 2010 ,2013, 2015:  Short term Visiting Professorship, Weizmann Institute, Rehovot, Israel
2011                          Nature Award for Mentoring in Science

Editorial Service
1982-1986                EMBO Journal, Editorial Board
1996                           EMBO Journal, Editor in chief
1991-present         Journal of Molecular Biology, Associate Editor
1995-1998               Journal of Virology, Editorial Board
2004-present         Genes to Cells, Editor
2006-present         Epigenetics, Editorial Board

Committees and Boards
1981-1984                 EMBO, Fellowship Committee
1991-1994                 General Motors Cancer Research Foundation Assembly, USA
1991-1996                 Member, EMBO Council
1992-1995                Vice Chairman, EMBO Council                                                                                                                                      1996                            Chairman, EMBO Council
1992-1995                 Member, Bio Avenir Committee
1992-1996                 EC, Human Capital and Mobility Life Science Group
1995-1998                 Member, Conseil Supérieur de la Recherche et de la Technologie
1995-2014                 Chairman, section of Biochemistry and Molecular Biology, Academia Europaea
1995-2003                 Cell Cycle and Nucleus selection panels, DFG, Bonn, Germany
1995-2000                 CNRS, Paris, Scientific Council, Life Sciences
1996-2000                 AICR, St Andrews, Scotland, Grant panel
1996-2000                 Human Frontiers Science Program, Fellowship Committee
1997-2000                 Association for Cancer Research, Villejuif, France, Scientific Council
1997-2002                 RIKEN Institute, Japan, Scientific Advisory Committee
1999-2000                 Chairman of the Scientific Council of the Institut Pasteur, Paris, France
2002-2005                 Scientific Advisory Board, Friedrich Miesher Institute, Basel, Switzerland
2004-2015                Co-founder and Chairman of the SAB, Anaconda Pharma, Paris
2004-                          Scientific Advisory Board, Institut European de Chimie et Biologie, Bordeaux
2015-                          Chair, SAB, Institut European de Chimie et Biologie, Bordeaux
2005-2011                Science Advisory Group, Cancer Research UK, London Research Institute
2005-2011                Scientific Advisory Board, Institut Pasteur, Korea
2005-                         Scientific Advisory Board, Fritz Lipmann Institute for Aging Research, Jena
2009-                         Chair, Scientific Advisory Board, Fritz Lipmann Institute for Aging Research
2006- 2011              Cancer UK, Funding Committee member
2006-2008               DFG, Bonn, Excellence Universities selection panel
2010-2014               Member Executive committee, European Association for Cancer Research
2010- 2014              Wellcome Trust, Interview Panel for senior grants

Publications: More than 300 in peer review journals
Citations:  25521;  h-index     91

Publications