Carl Nathan, TCOLF Trustee

Carl Nathan, MD is R.A. Rees Pritchett Professor and chairman of the Department of Microbiology and Immunology at Weill Cornell Medical College and co-chair of the Program in Immunology and Microbial Pathogenesis at Weill Graduate School of Medical Sciences of Cornell University. After graduation from Harvard College and Harvard Medical School, he trained in internal medicine and oncology at Massachusetts General Hospital, the National Cancer Institute and Yale before joining the faculty of The Rockefeller University from 1977-1986. He has been at Weill Cornell Medical College since 1986, where he has served as founding director of the Tri-Institutional MD-PhD Program, senior associate dean for research and acting dean. A member of the National Academy of Sciences, the Institute of Medicine of the National Academies and a Fellow of the American Academy of Microbiology, Nathan serves as associate scientific director of the Cancer Research Institute; a Trustee of the Hospital for Special Surgery and chair of the research committee; on the scientific advisory boards of the American Asthma Foundation, the Rita Allen Foundation and the Cambridge Institute for Medical Research; and since 1988, an editor of the Journal of Experimental Medicine. He received the Robert Koch Prize in 2009 for his work on host defense against infection.

In work spanning four decades Nathan established that lymphocyte products activate macrophages, that interferon-gamma is a major macrophage activating factor in mice and humans, and that mechanisms of macrophage antimicrobial activity include induction of the respiratory burst and inducible nitric oxide synthase (iNOS), which he and his colleagues purified, cloned, knocked out and characterized biochemically and functionally. Although iNOS helps the host control Mycobacterium tuberculosis, Mtb resists sterilization by host immunity. The biochemical basis of Mtb’s persistence is the lab’s present focus. Genetic and chemical screens have identified enzymes that Mtb requires to survive during non-replicative persistence, including the proteasome, a serine protease that controls intrabacterial pH, and components of pyruvate dehydrogenase and nucleotide excision repair, along with inhibitors of each.