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Ronald Collman, M.D.

Professor of Medicine
Professor of Medicine in Microbiology
Virus/Cell/Molecular Core Director, Penn Center for AIDS Research

University of Pennsylvania Medical Center
Pulmonary, Allergy & Critical Care Division
522 Johnson Pavilion
36th & Hamilton Walk
Philadelphia, PA 19104-6061
tel.: (215) 898-0913
fax: (215) 573-4446
email: collmanr@mail.med.upenn.edu

Education:

  • MD: Boston University School of Medicine
  • Residency: Temple University
  • Fellowship: Hospital of the University of Pennsylvania

Research Program:

Mechanisms of HIV-1 entry and target cell tropism

Program Summary:

My lab studies the molecular pathogenesis of HIV-1 infection. HIV-1 utilizes the chemokine receptors CCR5 and CXCR4 to enter target cells, including lymphocytes and macrophages. CCR5-using strains (R5) are responsible for person-to-person transmission, but virus evolves over time in infected people to use both CCR5 and CXCR4 (R5X4), in association with disease progresses.

Our work is directed at defining how these receptors are used by HIV-1 to enter target cells, how the viral Envelope glycoprotein regulates target cell tropism, and the molecular evolution of virus over time. We have found that virus isolates differ in their ability to use these entry pathways on target cells taken from different tissues, such as macrophages, blood lymphocytes, and tissue-derived lymphocytes. We are working to understand how the cellular context affects the manner in which virus uses the receptors, and how this influences disease progression.

A second area of interest is directed at understanding how HIV can lead to immune dysfunction independent of infection. In addition to serving as viral entry coreceptors, CCR5 and CXCR4 are potent signaling molecules. We have shown that the viral Envelope glycoprotein can act as a functional ligand for these receptors on macrophages, triggering intracellular signaling responses and cytokine secretion. We are working to determine the pathways activated by HIV-1 through these receptors, and how they alter macrophage function and contribute to disease.

Clinical Interest:

Pulmonary complications of HIV infection

Representative publications:

Isaacman-Beck, J., Hermann, E.A., Yi, Y., Ratcliffe, S.J., Mulenga, J., Allen, S., Hunter, E., Derdeyn, D., Collman, R.G.  Heterosexual transmission of HIV-1 Subtype C: Macrophage tropism, alternative coreceptor use, and the molecular anatomy of CCR5 utilization.  J. Virology. (in press).

Malik, M., Chen, Y.Y., Tomkowicz, B.E., Kienzle, M.F., Collman, R.G., Ptasznik, A. Monocyte migration and LFA1 mediated attachment to activated brain microvascular endothelial cells is regulated by SDF-1α through the SRC family kinase Lyn.  J. Immunology. 181(7), 4632-4637, 2008.

Cheung, R., Ravyn, V., Wang, L., Ptasznik, A., Collman, R.G.  Signaling mechanism of HIV-1 gp120 and virion-induced IL-1b release in primary human macrophages. J. Immunology. 180(10):6675-84, 2008.

Yi, Y., Loftin, L., Wang, L., Ratcliffe, S.J., Isaacman-Beck, J., Collman, R.G.  Entry coreceptor use and fusion inhibitor T20 sensitivity of dual-tropic R5X4 HIV-1 in primary macrophage infection.  J. Acquired Immune Deficiency Synd. 47(3):285-92, 2008.

Twigg, H.L., Weiden, M., Valentine, F., Schnizlein-Bick, C.T., Bassett, R., Wheat, J., Day, R.B., Rominger-Grubbs, H., Collman, R.G., Fox, L., Brizz, B., Dragavon, J., Coombs, R.W., Bucy, R.P., for the AIDS Clinical Trials Group Protocol 723 Team.  Effect of highly active antiretroviral therapy on viral burden in the lungs of HIV-infected subjects. J. Infectious Diseases. 197:109-116, 2008.

Tomkowicz, B., Lee, C., Ravyn, V., Cheung, R., Ptasznik, A., Collman, R.G.  The Src kinase lyn is required for CCR5 signaling in response to MIP-1b and R5 HIV-1 gp120 in human macrophages. Blood. 108:1145-50, 2006

Lee, C.,  Tomkowicz, B., Freedman, B.D.,  Collman, R.G.  HIV-1 gp120-induced TNF-a production by primary human macrophages is mediated by phosphatidylinositol-3 kinase and mitogen-activated protein kinase pathways.  J. Leukocyte Biol. 78:1016-1023, 2005.

Yi, Y., Shaheen, F., Collman, R.G.  Preferential use of CXCR4 by R5X4 HIV-1 isolates for infection of primary lymphocytes. J. Virol. 79:1480-1486, 2005.

revised 6/09



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