Request for Funding

Medical Student Research Fellowship for Summer 2001

Mentor: Jeanne S. Sheffield, M.D.

Department: Obstetrics & Gynecology

Room number: G6.230

Mail Code: 9032

Phone number: (214) 648-2646

E-mail: Jeanne.Sheffield@UTSouthwestern.edu

Project title: Genital ulcer disease and HIV transmission

Human subjects IRB approved project number (where applicable): Approval pending

Animal subjects IRB approved project number (where applicable): n/a

Project Type (patient-based research, animal-based research, or basic research; this characterization is only to permit a general classification for grouping similar types of projects) :

Translational research involving patient-based and basic research.

Brief Description of Project:

There is now compelling evidence that genital ulcer disease (GUD) is a significant risk factor for the bidirectional transmission of the human immunodeficiency virus type-1 (HIV-1). A number of biologic and molecular mechanisms have been proposed which likely account for a large percentage of the increased risk for both acquisition and increased infectiousness of HIV in the setting of GUD. In in vitro model systems, specific etiological agents responsible for GUD (e.g., HSV and Treponema pallidum) increase HIV replication, ostensibly promoting HIV infectiousness under normal transmission conditions. In vitro studies also recently have provided strong evidence of HIV-1 coreceptor upregulation after stimulation with T. pallidum or synthetic lipopeptides modeled after its proinflammatory membrane lipoproteins. There is, however, a paucity of in vivo data confirming many of the molecular findings garnered using in vitro model systems.

The overall objective of this project is to further elucidate the cellular and molecular bases of the interrelationship between GUD and HIV-1 transmission in both pregnant & nonpregnant women. Patients will be recruited from the STD Clinics, genital ulcer specimens will be obtained, and evaluation of HIV-1 coreceptor status performed using molecular and immunohistochemical techniques. This project encompasses clinical evaluation, study recruitment, and laboratory evaluation.

Previous Research Activities or Publications with Medical Students:

1. Carolyn Lee: Recovery of herpes simplex virus in women undergoing cesarean delivery

for genital herpes (June-August, 2000)

2. Ashley Hickman: Knowledge of sexually transmissable diseases in high-risk pregnancy

women (June-August, 2000)

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