Awardee 2012

Jean-Laurent Casanova

for his work on the genetics of childhood infectious diseases

Prof. Casanova is a pediatrician and immunologist by training, and has in practice become a human geneticist investigating infectious diseases. The fundamental question in the field of infectious diseases is that of interindividual, interfamilial, and interpopulation clinical heterogeneity in the course of primary infection: why does only a small minority of infected children develop clinical diseases? This question was first posed around 1910 and has yet to be answered for most infectious diseases in children. The microbe is necessary, but not sufficient for disease development, so what other factors are involved? Contrary to the prevailing view, the pathogenesis of severe pediatric infectious diseases remains obscure. According to the genetic theory of infectious diseases, human germline genetic variability leads to clinical variability; infectious diseases of childhood are thus also genetic traits. From the 1950s until recently, it was thought that mutations in a single gene conferred susceptibility to multiple infectious diseases (one gene, multiple infections), with common infections instead being associated with the inheritance of multiple susceptibility genes (multiple genes, one infection).
Prof. Casanova hypothesized that severe infectious disease of childhood results from collections of rare single-gene inborn errors of immunity. He has identified and characterized a new group of genetic defects that predispose otherwise healthy children to a single type of infection (one gene, one infection), a new causal relation­ship modifying a paradigm that has prevailed in this field for decades. He has deciphered the molecular genetic basis of various pediatric infectious diseases, including mycobacterial diseases (mutations in IFNGR1, IFNGR2, STAT1, IL12B, IL12RB1, NEMO, IRF8, CYBB, ISG15), invasive pneumococcal disease (NEMO, IKBA, IRAK4, MYD88, HOIL1), herpes simplex encephalitis (UNC93B1, TLR3, TRAF3, TRIF, TBK1), and chronic mucocutaneous candidiasis (IL17F, IL17RA, STAT1). These studies have important clinical implications, as they provide a basis for genetic counseling and a rationale for developing new therapeutic approaches based on an understanding of the host component of infectious diseases. These studies also have major biological implications, as they define the function of host defense genes in natura, in the setting of a natural ecosystem governed by natural selection.

1982-1987 M.Sc. (Biochemistry) – Jussieu Faculty of Sciences, University Paris Pierre et Marie Curie, France
1981-1987 M.D. (Medicine) – Cochin Medical School, University Paris Descartes, France
1988-1992 Ph.D. (Immunology) – Ludwig Institute for Cancer Research, Zurich, Switzerland, and Pasteur Institute, University Paris Pierre et Marie Curie, France
1992-1995 Residency (Pediatrics) – Hospitals of Paris, University Paris Descartes, France
1995-1999 Clinical Fellowship (Pediatric Immunology and Hematology) – Necker Medical School, University Paris Descartes, France
Postgraduate Training
1972-1974 Muscular Dystrophy Association Postdoctoral Research Fellow with Dr. Marshall Nirenberg, Laboratory of Biochemical Genetics, NHLBI, NIH
Professional Experience
1995-1999 Research Fellow, Laboratory of Primary Immunodeficiencies (head: Alain Fischer), Necker Hospital and School of Medicine, Univer­sity Paris Descartes, France
  Clinical Fellow, Pediatric Immunology and Hematology Unit (head: Claude Griscelli and later Alain Fischer), Necker Hospital, Paris, France
1999-2008 Professor of Pediatrics, Pediatric Immunology-Hematology Unit (head: A. Fischer), Necker Hospital and School of Medicine, University Paris Descartes, France
  Head of Laboratory (with Laurent Abel), Laboratory of Human Genetics of Infectious Diseases, Necker Branch, Necker School of Medicine, University Paris Descartes, France
2008-present Professor, The Rockefeller University, New York, USA
  Head of Laboratory, St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, New York, USA
  Senior Attending Physician, Rockefeller University Hospital, New York, USA
  Visiting Professor, Necker Hospital and School of Medicine, University Paris Descartes, France