Treatment and Prevention of HIV/AIDS

Description of projects available to graduate students:
My research program is dedicated toward preventing, treating and curing HIV infection. Past work has provided critical insight into the relation between viremia and HIV disease progression, helped develop the first long-term effective antiretroviral therapy for HIV infection, and defined the genetic and biochemical basis for HIV resistance to nucleoside and non-nucleoside inhibitors of HIV-1 reverse transcriptase. More recent research projects focus on preventing HIV-1 infection through the use of antiretrovirals and on quantifying persistent HIV reservoirs in patients on antiretroviral therapy with the long-term goal of reducing or eliminating them.

Students and fellows in my laboratory use the latest techniques in molecular biology (qPCR, single genome sequencing, cloning, mutagenesis) and virology to detect, quantify and characterize HIV-1 variants that are resistant to antiretrovirals or that persist despite effective antiretroviral therapy

Students, fellows and staff in my laboratory have made major contributions to the fields of antiretroviral therapy and drug resistance, including the first to characterize HIV resistance several nucleoside, non-nucleoside and pyrophosphate analogs. Recent discoveries include more potent nucleoside analog reverse transcriptase inhibitors, antagonistic interactions between drug resistance mutations, novel mechanisms of drug resistance involving the connection and RNAse H domains of reverse transcriptase, the important role of low frequency drug resistant variant in failure of antiretroviral therapy, and the persistence of HIV-1 viremia in most patients despite long-term antiretroviral therapy.

Projects in my lab that are open to new students are:

1. Defining the molecular basis and clinical significance of resistance to reverse transcriptase inhibitors

2. Characterizing the activity, mechanism of action, and toxicity profile of new reverse transcriptase inhibitors.

3. Identifying the persistent anatomic and cellular reservoirs of HIV in patients on suppressive antiretroviral therapy.

4. Evaluating interventions to eliminate HIV reservoirs.

The laboratory is currently comprised of 2 postdoctoral fellows, 4 doctoral students, and 4 research technicians.

Techniques graduate student will learn:
Techniques graduate student will learn include:
cell and virus culture, antiviral drug susceptibility assays, cytoxicity assays, molecular cloning, site-directed mutagenesis, DNA sequencing, standard and real-time RT-PCR, allele-specific PCR, single genome sequencing, enzyme biochemistry, molecular modeling, drug evaluation and development.