Inflammation and HIV disease: the role of tryptophan catabolism

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Joseph M. ("Mike") McCune, MD, PhD
Professor of Medicine
Chief of the Division of Experimental Medicine
University of California, San Francisco

Mike McCune is a Professor of Medicine and Chief of the Division of Experimental Medicine. He received his AB from Harvard College (1975), his PhD from Rockefeller University (1981), and his MD from Cornell University Medical College (1982). He completed his residency in internal medicine (1984), did fellowship training in infectious diseases at University of California at San Francisco (UCSF), and is board certified in internal medicine. After post-doctoral work at Stanford in the Department of Pathology (1988), he was a founder and the Chief Executive Officer of SyStemix, Inc., and then served as its Vice President, Research and Development until 1991. He started this biotechnology company to optimize and to standardize the use of “humanized mice” (which he invented while at Stanford) for the discovery of human hematopoietic stem cells and for the preclinical development of effective antiretroviral therapies, including gene therapy, against HIV. Thereafter and until his move to the Gladstone Institute of Virology and Immunology/UCSF in 1995, he was Vice President of the New Enterprise Research Division (an exploratory research group), a member of the Partnership Committee of Progenesys (a joint venture that he founded between SyStemix and Sandoz, aimed at developing hematopoietic stem cell-based gene therapies for HIV disease), and a Clinical Associate at UCSF (working at the San Francisco General Hospital AIDS Clinic).

His past research has focused on the definition of pathogenic mechanisms of viral diseases, particularly HIV disease. This focus has spanned a range of fields, from understanding critical structural determinants of infectivity, to devising a small animal model (the SCID-hu Thy/Liv mouse) to study HIV pathogenesis and to prioritize antiretroviral compounds against HIV, to studying mechanisms of T cell depletion and repletion in vivo. Throughout this body of work, he has engaged in hypothesis-driven, patient-oriented research that has involved collaborative teams of basic scientists, translational researchers, and clinicians. More recently, and as a consequence of a sabbatical year at the Institut Pasteur (2003-04), he has devoted all of his attention to understanding the correlates of protective immunity against HIV, with the specific intent to work with others to eradicate HIV from infected individuals and to end the AIDS epidemic once and for all. This change of focus has now been materialized at UCSF by the creation of the Division of Experimental Medicine, of which Dr. McCune is the Chief. From 2005-2008, he concomitantly served as the founding Principal Investigator and Director of the Clinical and Translational Science Institute at UCSF, an organization whose mission is to enhance and to facilitate the process by which better therapies can be brought from the lab bench to the community more quickly. In this capacity, he served as the Senior Associate Dean of Clinical and Translational Research in the Schools of Dentistry, Medicine, Nursing, and Pharmacy at UCSF.

Dr. McCune’s studies have led to the publication of over 200 peer-reviewed articles and he is the holder of 20 patents and inventions. On the basis of this work, he was awarded the Elizabeth Glaser Pediatric AIDS Foundation Scientist Award in 1996, the Burroughs Wellcome Fund Clinical Scientist Award in Translational Research in 2000, a MERIT Award from the NIH in 2001, the NIH Director’s Pioneer Award in 2004, a Gates Grand Challenges Explorations Phase II Award in 2011, and a number of mentoring awards for his activities with junior faculty, postdoctoral fellows, and graduate students. He is a member of many scientific and professional societies, including the American Society for Clinical Investigation, the American Association of Physicians, and the Henry Kunkel Society. He has also served on the editorial boards of multiple scientific journals.

His current activities embrace and are motivated by the experiences of 30 years of work in the HIV epidemic. In the case of the Division of Experimental Medicine, he has created a multidisciplinary, collaborative environment for the analysis of the human immunology of chronic infectious diseases of medical importance, including those caused by HIV, TB, malaria, and helminthic worms. The underlying hypothesis of the Division is that each of these agents has evolved patterns of interaction with the host which, in most cases, do not lead to overt disease; that these patterns are likely to embrace protective immune responses with mechanistic overlaps; and that elucidation of such common patterns of successful host-pathogen interaction may inform the development of interventions (e.g., vaccines and medicines) to successfully fight HIV. The Division is also established to train individuals in the processes of collaborative, multidisciplinary, patient-oriented research and to serve as a model for other research units that might be focused on other human disease states.

His focus now is to eradicate HIV from infected individuals who must otherwise take life-long antiretroviral therapy. With his colleagues, Drs. Steve Deeks and Rafick Sekaly, he is leading a worldwide consortium of scientists that is addressing a number of hypotheses about how eradication might be achieved. This work is enabled by a bridging network of basic research labs and venues for clinical investigation, many of which Dr. McCune helped to build. He wishes to achieve the type of survival rates, off antiretroviral medications, that are currently available to those who are uninfected. He anticipates that this will involve not only the addition of orally available adjunctive therapies to the existing antiretroviral medications, but also the creation of therapeutic interventions that will prompt effective host responses against HIV. He believes that this effort will eventually lead not only to the eradication (“cure”) of HIV within those who are infected, but also to the development of vaccines to prevent infection of those who are not. Not less importantly, he believes that the preventative and therapeutic interventions that serve to eradicate HIV may be applied to the treatment of other chronic infectious diseases (e.g., those caused by tuberculosis, malaria, and helminthic worms) and possibly even to the treatment of other chronic conditions that, like HIV, are accompanied by a state of aberrant inflammation (e.g., autoimmune diseases, atherosclerosis, malignancies, dementia, and obesity).

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