Research Interests
Throughout evolution, humans have been challenged by viral pathogens new to the species. For the most part, our immune system mounts an adequate response that protects us from the fatal consequences of infection. However, in some instances viruses can circumvent the immune system and cause fatal diseases such as cancer (EBV, KSHV, HCV), hemorrhagic fever (Ebola virus) and AIDS (HIV). Understanding the host pathogen relationship at a molecular level provides rational approaches to therapy and vaccine development. In addition, it also provides a better understanding of human biology. We are interested in how human viruses cause human cancer, how HIV causes AIDS and why the immune system is not able to control viral infections. Our working hypothesis is that specific viral genes are the key determinants of viral pathogenesis and are responsible for disease progression. To evaluate the role of these genes in disease progression, we have developed in vitro and in vivo models that recapitulate specific aspects of viral infection. Our emphasis has been placed on humanized mice as models where human specific pathogens can be studied and where novel therapeutic interventions can be evaluated. For example, lymphotropic viruses are responsible for a vast number of human cancers. Unfortunately, their study has been severely limited due to fact that the majority of these viruses do not infect other mammals. Thus the lack of animal models susceptible to infection by these human viruses has severely limited our ability to develop novel treatments and effective vaccines. Our laboratory has established novel animal models that recapitulate key aspect of infection by human-specific viruses such as EBV, HIV, HHV-8 and dengue virus. We are currently using these systems to evaluate novel interventions to treat and/or prevent the devastating diseases caused by these agents.

Training
Instituto Technologico y de Estudios, Superiores de Monterray, Mexico B.Sc. 1979 Chemistry
Georgetown University, Washington, D.C. Ph.D. 1984 Chemistry/Biochemistry
National Cancer Institute, NIH Fellow 1984-85 Biology/Immunology
Massachusetts Institute of Tech., Boston, MA Fellow 1985-87 Cell Biology
Fred Hutchinson Cancer Ctr., Seattle, WA Res. Assoc. 1987-92 Human Gene Therapy

Publications
Musk P, Szamania S, Galloway A, Johnson K, Scott A, Ta N, Guttman S, Bridges K, Bruorton M, Gatlin J, Garcia JV, Lamb L, Chian KY, Spencer T, Henslee-Downey J and Rhee FV. EBV-specific cytotoxic T cells for prevention of EBV-induced lymphoma in haplo-identical allogeneic stem cell transplantation. J. Immunotherapy 24, 312-322 (2001).

Islas-Ohlmayer M, Padgett-Thomas A, Domiati-Saad R, Melkus MW, Cravens PD, Martin M del P, Netto G, and Garcia JV. Experimental Infection of NOD/SCID Mice Reconstituted with Human CD34+ Cells with Epstein-Barr Virus. J. Virol. 78, 13891-13900 (2004).

Wei B, Arora VK, Raney A, Kuo L, Xiao G-H, ONeill E, Testa JR, Foster JL and Garcia JV. Activation of p21-activated kinase by human immunodeficiency virus type-1 Nef induces merlin phosphorylation. J. Virology. 79, 14976-14980 (2005).

Melkus MW, Estes JD, Padgett-Thomas A, Gatlin J, Denton PW, Othieno F, Wege AK, Hasse AT, and Garcia JV. Humanized mice mount specific adaptive and innate immune response to EBV and TSST-1. Nature Medicine. 12, 1322-1326 (2006).

Sun Z, Denton PW, Estes JD, Othieno F, Wei B, Wege AK, Melkus MW, Padgett-Thomas A, Zupancic M, Haase AT and Garcia JV. Intrarectal transmission, systemic infection and CD4 T cell depletion in humanized mice infected with HIV-1. J. Exp. Med. 204, 705-714 (2007).

Denton PW, Estes JD, Sun Z, Othieno F, Wei B, Wege AK, Powell DA, Payne D, Haase AT and Garcia JV. Antiretroviral Pre-exposure Prophylaxis Prevents Vaginal Transmission of HIV-1 in Humanized BLT Mice. PLoS Medicine Vol. 5, No. 1, e16 doi:10.1371 (2008).

E-mail: victor_garcia@med.unc.edu
Telephone: 843-9601
FAX: 966-6870
Address: 2044 Genetic Medicine Building Chapel Hill, NC 27599

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