Medical Student Research Fellowship for Summer 2008

Mentor: Dr. J. Victor Garcia
Department: Internal Medicine
Room number: Y9.206
Mail Code: 9114
Phone number: 214-648-9970
E-mail: Victor.Garcia@utsouthwestern.edu
Project title: Novel Approaches for the Prevention of Vaginal HIV Transmission

Human subjects IRB approved project number (where applicable): 1099-479

Animal subjects IRB approved project number (where applicable): 0855-07-11-1

Project Type Basic research

Brief Description of Project:
In the absence of an effective vaccine to prevent HIV infection other preventive options such as the use of topical microbicides have been explored. Unfortunately, despite extensive in vitro efficacy testing and any lack of overt toxicity in phase I clinical trials virtually all first generation of microbicides either failed efficacy trials or were shown to increase the risk of infection. Therefore alternative approaches must be considered. Dr. Garcia's laboratory has developed a novel system designated BLT mice (for bone marrow/liver/thymus) for the in vivo analysis of mucosal HIV-1 transmission (Melkus et al Nature Medicine, Sun et al J. Exp. Med., Denton et al PLoS Medicine). My summer research project will be to test the ability of a novel HIV-1 inhibitor, PSC-RANTES to prevent vaginal HIV-1 transmission in this model. For this purpose, I will first construct BLT mice and characterize their reconstitution with human cells, second I will challenge these mice after vaginal application of PSC-RANTES or placebo, and third I will determine HIV-1 transmission by both molecular and immunological techniques. I intend to show that the results obtained in humanized BLT mice clearly reflect the ultimate effectiveness previously seen in either non-human primate models. These results will serve to provide proof of principle of usefulness of topically applied microbicides to prevent vaginal HIV-1 transmission. In addition, these pre-clinical studies will also provide further evidence that the BLT model can serve as an outstanding platform for the in vivo evaluation of novel and highly effective approaches aimed at stopping the spread of AIDS.

Previous Research Activities or Publications with Medical Students: