| Abstract |
Dr. Ramratnam’s focus will be on
antiretroviral therapeutics. Dr. Ramratnam's research has
focused on the problem of persistent HIV-1 virus replication
in the presence of therapeutic plasma drug concentrations.
It has been demonstrated that HIV-1 protease (PI) and nucleoside
reverse transcriptase inhibitors (NRTI) are substrates of
ATP Binding Cassette (ABC) Transporter Proteins such as P-glycoprotein
(Pgp) and Multi-drug Resistant Protein (MRP). These proteins
serve to non-specifically extrude a variety of compounds from
inside the cell. Cells high in Pgp expression also line the
gastrointestinal tract and blood brain barrier and decrease
the transit of certain drugs across these sites. P-gp expression
has been demonstrated in CD4+ T lymphocytes isolated from
HIV-1 infected individuals. The antiviral efficacy of PI's
is decreased in cells expressing Pgp, in vitro. Among proteins
belonging to the MRP class, MRP4 and MRP5 extrude NRTI's from
inside the cell and thereby decrease their antiviral efficacy,
in vitro. Dr. Ramratnam will investigate whether virus replication
during antiretroviral therapy originates from cells expressing
Pgp/MRP. His laboratory will seek to identify and clinically
evaluate antiretroviral drugs that are not substrates for
Pgp/MRP. Such agents may be far more effective in reducing
total HIV-1 burden and controlling virus replication.
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