专家人才库数据----中国科学院上海巴斯德研究所

Principal investigator2016

Name:	Sansonetti, Philippe J	Gender:
Education:	Internal Medicine, Faculty of Medicine, Paris, France (1979) MS, Biochemistry/Microbiology, Faculté des Sciences, Paris 7, France (1976)
Academic degree:	M.D.	Academic title:	Principal Investigator
Departments:	Microbial Molecular Pathogenesis and Symbiosis	Discipline:	Microbiology
Phone:		E-mail:	philippe.sansonetti@ips.ac.cn
Mailing Address:	Life Science Research Building No.320 Yueyang Road, Xuhui District, 200031 Shanghai

Curriculum vitae:

2019- 2019 - 2021 2008 -	Pricipal Investigator, Chief Scientist of The Center for Microbes in Development and Health Institut Pasteur of Shanghai, Chinese Academy of Science Emeritus Professor, Institut Pasteur Professeur titulaire, Chaire de Microbiologie et Maladies Infectieuses, Collège de France
2005 - 2019	Director of INSERM UNIT 786 (2005-2013) and 1202 (2013-2019)
2000 - 2019	Professor of exceptional class, Institut Pasteur
1995 - 2000	Medical Director, Institut Pasteur, Paris, France
1994 - 2000	Professor, Institut Pasteur
1989 -	Head of Unité de Pathogénie Microbienne Moléculaire, Institut Pasteur, Paris, France
1985 - 1995	Head, Out-patient Clinic, Institut Pasteur Hospital, Paris, France
1983 - 1987	Researcher at the Institut Pasteur at the Institut Pasteur Hospital, Paris, France
1981 - 1985	Head of Clinic-Assistant, Institut Pasteur Hospital, Paris, France

1979 – 1981 Postdoctoral Fellow Walter Reed Army Institute of Research, Washington DC, USA

Research direction:
Medicine, particularly infectiology, has been my constant source of inspiration and stimulation in research. It is an endless resource of questions and challenges. I have made basic discoveries that have forged the multidisciplinary field of microbial pathogenesis, while also developing translational research programs largely aimed at improving health of children in the most impoverished areas of the planet, well in line with the pasteurian tradition. My research is focused on: 1) Basic research on *Shigella* pathogenesis 2) *Shigella* vaccine development 3) Gut microbiome, from homeostasis to disease 4) Translational research

Research direction:

Medicine, particularly infectiology, has been my constant source of inspiration and stimulation in research. It is an endless resource of questions and challenges. I have made basic discoveries that have forged the multidisciplinary field of microbial pathogenesis, while also developing translational research programs largely aimed at improving health of children in the most impoverished areas of the planet, well in line with the pasteurian tradition. My research is focused on:

1) Basic research on Shigella pathogenesis

2) Shigella vaccine development

3) Gut microbiome, from homeostasis to disease

4) Translational research

Research progress:
1) Basic research on *Shigella* pathogenesis I am among those who pioneered molecular pathogenesis of infections, using the invasive enteric pathogen Shigella that I established as a model. I have contributed detailed understanding of the molecular mechanisms of Shigella pathogenesis. We eventually provided a unique integrative view of infection, in vitro and in vivo, leading to better understanding how the host senses the bacterial danger and how the pathogen uses and subverts innate immune responses to respectively disrupt the epithelial barrier and survive humoral and cellular immune effectors. This succession of original discoveries set the basis of a novel model of interdisciplinary study of infections, also known as “cellular microbiology”. Our recent successive discoveries represent a true “second breath’ of Shigella research and are of more global value in the study of bacterial pathogenesis. 2) *Shigella* vaccine development I was the first to develop a vaccine against shigellosis by rational genetic attenuation of virulence based upon the knowledge our group had accumulated on the genetic bases of cell and tissue invasion. These candidate vaccines have successfully gone through phase 1 and 2 clinical trials in USA, UK and France. In 2009, I was successful in being awarded the coordination of a major European-Union funded grant (12 million Euros) - STOPENTERICS - to hasten the conception and clinical development of a novel generation of vaccines against Enterotoxigenic Escherichia coli (ETEC) and Shigella, the two major causes of severe enteric infections in the developing world. Following this program, a novel prototype of conjugate vaccine in which the somatic/serotype specific O- polysaccharides are chemically synthesized has now provided evidence of excellent tolerance and strong immunogenicity in a phase 1 trial. Thanks to a large scale grant of the Bill and Melinda Gates Fundation, the program will now move to phases 2/3 in sub-saharan Africa. 3) Gut microbiome, from homeostasis to disease In the past 10 years, thanks to the support of the Howard Hughes Medical Institute and the successive award of two prestigious European Council (ERC) Advanced grants respectively called HOMEOEPITH and DECRYPT, I started to tackle the field of bacterial symbiosis, with the aim of switching it from descriptive metagenomics to a true mechanistic “cellular microbiology of symbiosis”, capitalizing on our work on pathogens to identify the molecular cross-talks achieving symbiotic/mutualistic interactions between the gut mucosa and the microbiome - “from metagenomics to experimentomics” - particularly how bacteria of the gut microbiome regulate epithelial homeostasis. 4) Translational research On these basis, in addition to our vaccine programs, we develop several translational projects such as: a discovery program of molecules stimulating the expression of epithelial antimicrobial peptides; a parallel clinical study on gut bacterial translocation in leukemic patients in bone marrow aplasia following chemotherapy and how it relates to the bactericidal role of antimicrobial peptides.We have also initiated an ambitious study of the pathogenesis of Pediatric Environmental Enteropathy (PEE) in sub-Saharans Africa (Central African Republic and Madagascar). Our study –MICROBIOTA – is largely aimed at identifying the composition of this dysbiosis and, in this basis, disentangle the pathogenesis of PEE and offer biomarkers for early detection, as well as preventive and therapeutic solutions to eliminate stunting and psychomotor retardation that are the dominant consequences of PEE. In Summary, I have made basic discoveries that have forged the multidisciplinary field of microbial pathogenesis, while also developing translational research programs largely aimed at improving health of children in the most impoverished areas of the planet, well in line with the pasteurian tradition. My work has been recognized by numerous awards and I am an elected member of national and international organisations, including EMBO, the French Academy of Sciences, The Royal Society and the US National Academy of Sciences.

Research progress:

1) Basic research on Shigella pathogenesis

I am among those who pioneered molecular pathogenesis of infections, using the invasive enteric pathogen Shigella that I established as a model. I have contributed detailed understanding of the molecular mechanisms of Shigella pathogenesis. We eventually provided a unique integrative view of infection, in vitro and in vivo, leading to better understanding how the host senses the bacterial danger and how the pathogen uses and subverts innate immune responses to respectively disrupt the epithelial barrier and survive humoral and cellular immune effectors. This succession of original discoveries set the basis of a novel model of interdisciplinary study of infections, also known as “cellular microbiology”. Our recent successive discoveries represent a true “second breath’ of Shigella research and are of more global value in the study of bacterial pathogenesis.

2) Shigella vaccine development

I was the first to develop a vaccine against shigellosis by rational genetic attenuation of virulence based upon the knowledge our group had accumulated on the genetic bases of cell and tissue invasion. These candidate vaccines have successfully gone through phase 1 and 2 clinical trials in USA, UK and France. In 2009, I was successful in being awarded the coordination of a major European-Union funded grant (12 million Euros) - STOPENTERICS - to hasten the conception and clinical development of a novel generation of vaccines against Enterotoxigenic Escherichia coli (ETEC) and Shigella, the two major causes of severe enteric infections in the developing world. Following this program, a novel prototype of conjugate vaccine in which the somatic/serotype specific O- polysaccharides are chemically synthesized has now provided evidence of excellent tolerance and strong immunogenicity in a phase 1 trial. Thanks to a large scale grant of the Bill and Melinda Gates Fundation, the program will now move to phases 2/3 in sub-saharan Africa.

3) Gut microbiome, from homeostasis to disease

In the past 10 years, thanks to the support of the Howard Hughes Medical Institute and the successive award of two prestigious European Council (ERC) Advanced grants respectively called HOMEOEPITH and DECRYPT, I started to tackle the field of bacterial symbiosis, with the aim of switching it from descriptive metagenomics to a true mechanistic “cellular microbiology of symbiosis”, capitalizing on our work on pathogens to identify the molecular cross-talks achieving symbiotic/mutualistic interactions between the gut mucosa and the microbiome - “from metagenomics to experimentomics” - particularly how bacteria of the gut microbiome regulate epithelial homeostasis.

4) Translational research

On these basis, in addition to our vaccine programs, we develop several translational projects such as: a discovery program of molecules stimulating the expression of epithelial antimicrobial peptides; a parallel clinical study on gut bacterial translocation in leukemic patients in bone marrow aplasia following chemotherapy and how it relates to the bactericidal role of antimicrobial peptides.We have also initiated an ambitious study of the pathogenesis of Pediatric Environmental Enteropathy (PEE) in sub-Saharans Africa (Central African Republic and Madagascar). Our study –MICROBIOTA – is largely aimed at identifying the composition of this dysbiosis and, in this basis, disentangle the pathogenesis of PEE and offer biomarkers for early detection, as well as preventive and therapeutic solutions to eliminate stunting and psychomotor retardation that are the dominant consequences of PEE.

In Summary, I have made basic discoveries that have forged the multidisciplinary field of microbial pathogenesis, while also developing translational research programs largely aimed at improving health of children in the most impoverished areas of the planet, well in line with the pasteurian tradition. My work has been recognized by numerous awards and I am an elected member of national and international organisations, including EMBO, the French Academy of Sciences, The Royal Society and the US National Academy of Sciences.

Laboratory members: