Proceedings of the National Academy of Sciences of the United States of America

About the PNAS Member Editor
Name Nathan, Carl F.
Location Cornell University
Primary Field Immunology and Inflammation
Secondary Field Microbial Biology
 Election Citation
Nathan discovered a host defense pathway by which lymphocyte-derived cytokines activate macrophages. He identified interferon-(gamma) as a principal macrophage activating factor that induces phagocyte oxidase and inducible nitric oxide synthase (iNOS); purified, cloned and knocked out iNOS, revealing its broad role; and discovered pathways by which microbes resist its actions.
 Research Interests
My research deals with the basis of host defense at immunological and biochemical levels and the implications for therapy. Over four decades I established that lymphocyte products activate macrophages, that interferon-gamma is a major macrophage activating factor (which I helped introduce into clinical use), and that mechanisms of macrophage antimicrobial activity include induction of the respiratory burst and inducible nitric oxide synthase (iNOS). My colleagues and I purified, cloned, knocked out and characterized iNOS biochemically and functionally, discovered the cofactor role of tetrahydrobiopterin in NOS's and introduced iNOS as a potential target in diseases such as Alzheimer's. Although iNOS helps the host control Mycobacterium tuberculosis, the leading cause of death from bacterial infection, Mtb resists sterilization by host immunity. We are now studying the biochemical basis of Mtb's persistence. 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 that also serve in peroxynitrite reductase. We are identifying compounds that kill non-replicating bacteria and using this as an opportunity to test new collaborative models between academia and industry.

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