Immunology Graduate Program | University of California, San Francisco

Joseph (Mike) McCune, MD, PhD

HIV Immunopathogenesis

Professor of Medicine
Chief, Division of Experimental Medicine
Senior Associate Dean of Clinical and Translational Research
UCSF Box 1234
San Francisco, CA 94143-1234

(415) 206-8101 office
(415) 206-8091 fax
Email

AA: Olive Burk, 206-5765

Description of Research

The main research focus of my laboratory is 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 (McCune et al., Cell 1988), to devising a small animal model (the SCID-hu Thy/Liv mouse) to study HIV pathogenesis and to prioritize antiretroviral compounds against HIV (McCune et al., Science 1988a, 1988b, 1990), to studying mechanisms of T cell depletion and repletion in vivo (Bonyhadi et al., Nature 1993; Su et al., Immunity 1995; Komanduri et al., Nature Medicine 1998; Hellerstein et al., Nature Medicine 1998; Stoddart et al., Nature Medicine 2001; McCune Nature 2001). Throughout this body of work, hypothesis-driven, patient-oriented research has been pursued with collaborative teams of basic scientists, translational researchers, and clinicians. Most recently, ever more attention has been devoted to understanding the correlates of protective immunity against HIV, with the specific intent to work with others to develop an effective vaccine. This change of focus has now been materialized by the creation of the Division of Experimental Medicine.

The Division will grow over the next several years to include 7-8 labs, led by scientists who are doing cutting edge research on the immunology of HIV disease and/or of other chronic infectious diseases (for instance, tuberculosis, malaria, and hepatitis) that afflict people with HIV disease around the world. Its overall goal is to better understand the means by which the strengths of the human immune system can be garnered to fight HIV as well as these other infectious agents. With this knowledge, we hope to facilitate and expedite the development of effective vaccines against all of them.

At the same time, we are involved in the creation of the UCSF Clinical and Translational Sciences Institute, a multidisciplinary effort spanning each of the four UCSF professional schools and aimed at facilitating the process by which better therapies can be moved from the lab bench to the clinic.

McCune JM . The dynamics of CD4+ T-cell depletion in HIV disease. Nature 410:974-979, 2001.

Napolitano LA, Grant RM, Deeks SG, Schmidt D, De Rosa SC, Herzenberg LA, Herndier BG, Andersson J, McCune JM . Increased production of IL-7 accompanies HIV-1-mediated T-cell depletion: implications for T-cell homeostasis. Nature Med. 7:73-79, 2001.

Stoddart CA, Liegler TJ, Mammano F, Linquist-Stepps VD, Hayden MS, Deeks SG, Grant RM, Clavel F, McCune JM . Impaired replication of protease inhibitor-resistant HIV-1 in human thymus. Nature Med. 7: 712-718, 2001.

Hellerstein MK, Hoh RA, Hanley MB, Cesar D, Lee D, Neese RA, McCune JM . Subpopulations of long-lived and short-lived T-cells in advanced HIV-1 infection. J. Clin. Invest. 112: 956-966, 2003.

Lee MS, Hanspers K, Barker CS, Korn AP, McCune JM . Gene expression profiles during human CD4+ T cell differentiation. International Immunol, 16:1109-24, 2004.

Deeks SG, Martin JN, Sinclair E, Harris J, Neilands T, Maecker HT, Hagos E, Wrin T, Petropoulos CJ, Bredt B, McCune JM . Strong cell-mediated immune responses are associated with the maintenance of low-level viremia in antiretroviral-treated individuals with drug-resistant human immunodeficiency virus type 1. J. Infect. Dis. 189:312-21, 2004.

Roy AM, Schweighardt B, Eckstein LA, Goldsmith MA, McCune JM. Enhanced replication of R5 HIV-1 over X4 HIV-1 in CD4(+)CCR5(+)CXCR4(+) T cells. J Acquir Immune Defic Syndr . 2005 Nov 1;40(3):267-75.

Baum PD and McCune JM. Direct measurement of T cell receptor repertoire diversity with AmpliCot: a novel automated assay that measures the sequence diversity of PCR products. Nature Methods, 3:895-901, 2006.

Hartigan-O¹Connor D, Poon CK, Sinclair E, McCune JM. Human CD4+ regulatory T cells express lower levels of the IL-7 receptor alpha chain (CD127), allowing consistent identification and sorting of live cells. J Immunol Methods 30:41-52, 2007.

Miller CJ, Genesca M, Abel K, Montefiore D, Forthal D, Bost K, Li J, Favre D, McCune JM. Antiviral antibodies are necessary for control of SIV replication. J Virol, 81:5024-35, 2007.

Hartigan-O¹Connor D, Abel K, McCune JM. Suppression of SIV-specific CD4+ T cells by infant but not adult macaque regulatory T cells: implications for SIV disease progression, J Exp Med, in press, 2007.