The rockefeller university

Jean-Laurent Casanova, a distinguished pediatrician and immunologist, will join the faculty at The Rockefeller University as professor of medicine and head of the Laboratory of Human Genetics of Infectious Diseases in September 2008.

Casanova, who comes from Hospital Necker for Sick Children in Paris, has identified genetic mutations that predispose individuals to specific pathogens, a finding that has both challenged and brought together divergent theories in the field of immunology. With this unified conceptual framework, Casanova has provided experimental evidence for a new perspective for understanding why some children get sick during the course of infection while others exposed to the same pathogen do not. This has paved the way for developing treatments that are based on a rational understanding of the human genetics of infectious diseases.

“Dr. Casanova’s research has forced scientists to reexamine accepted ideas in immunology and clinical medicine,” says Rockefeller president Paul Nurse. “This innovative approach to translational research cuts across many fields and opens up new and exciting opportunities for collaboration.”

As a clinical scientist, Casanova will establish part of his research program at The Rockefeller University Hospital and the Center for Clinical and Translational Science, where he will recruit children from around the globe who are selectively predisposed to developing infectious diseases, particularly tuberculosis, invasive pneumococcal diseases and herpes simplex encephalitis. By studying the immune systems of these children, Casanova will work to identify genetic lesions that confer this vulnerability and to prove that, as a rule, life-threatening infectious diseases in children are caused by mutations in a single gene.

“We’ve shown that these genetic mutations are like ‘Mendelian holes’ in the defense against specific pathogens,” says Casanova. “The goal is to learn where they exist in certain diseases and then try to patch them up by restoring the missing element.”

Casanova and his colleague Laurent Abel now have a better idea of where to look for these mutations. Recently, they found that mutations in various immune system pathways tend to make children susceptible to specific pathogens. In this context, they found that children who are prone to tuberculosis do not produce enough of the chemical that thwarts tuberculosis-causing bacteria, whereas children prone to herpes simplex encephalitis do not produce enough of the chemical that thwarts the virus responsible for that disease. By restoring this deficient response in patients, Casanova has shown that they can significantly benefit from this treatment.

In the case of herpes simplex encephalitis, Casanova has already identified two genes that can predispose children to the infection. At Rockefeller, Casanova aims to decipher the entire genetic basis of herpes simplex encephalitis and identify alleles that make children susceptible to the disease. He will also continue to test various infectious diseases and prove, for each, that one specific pathway is primarily altered.

“Certain human genes exert an almost pathogen-specific effect in protective immunity,” says Casanova. “This raises the exciting possibility that animals and microbes coevolved just as plants and pathogens did. Those that developed resistance to these pathogens lived on.”

Casanova received his M.D. in 1987 from the University of Paris René Descartes and his Ph.D. in immunology from the Pasteur Institute in Paris and the Ludwig Institute for Cancer Research in Lausanne in 1992. He is currently professor of pediatrics and, with Laurent Abel, director of the Laboratory of Human Genetics of Infectious Disease at the Necker Medical School Hospital for Sick Children in Paris. In 2004, he received the Professor Lucien Dautrebande Prize from the Belgian Royal Academy of Medicine and, in 2008, the Richard Lounsbery Award from the French and American Academies of Sciences.