Medical Student Research Fellowship for Summer 2008

Mentor: Julie Pfeiffer
Department: Microbiology
Room number: NA6.602
Mail Code: 9048
Phone number: 214-648-7319
E-mail: Julie.Pfeiffer@UTSouthwestern.edu
Project title: Ribavirin uptake in human blood

Human subjects IRB approved project number (where applicable):

082006-081 and 082007-080

Animal subjects IRB approved project number (where applicable): None

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)

Brief Description of Project:

In the U.S., approximately 4 million people are infected with hepatitis C virus (HCV). Unfortunately, half of HCV patients do not respond to the current interferon/ribavirin therapy, and most of these patients develop chronic liver disease. Factors that contribute to treatment failure are of great interest, but are currently not well defined. The role of ribavirin (RBV), a nucleoside analog, in HCV clearance is surprisingly understudied. Although there are several proposed mechanisms for RBV's antiviral activity, all likely require RBV import into cells. The goal of this project is to test a novel hypothesis; that RBV uptake may be an unappreciated factor that markedly affects the overall efficacy of treatment. We hypothesize that treatment response correlates with cellular RBV import, and that patients may become resistant over time, due to RBV toxicity. If even a few hepatocytes become RBV resistant during therapy, then these cells could produce high quantities of virus, possibly resulting in treatment failure. We will measure RBV uptake levels in peripheral blood mononuclear cells (PBMCs) from healthy volunteers, and from treatment responding vs. non-responding HCV patients to determine whether RBV uptake correlates with treatment response. This work has the potential to aid prediction of treatment response and guide the development of new diagnostics to facilitate tailored, individualized therapy to boost treatment response.

Previous Research Activities or Publications with Medical Students: None