1015 Walnut Street
Philadelphia, PA 19107
B.S.-M.Sc., Biochemistry/Clinical Chemistry, University of Sofia, Bulgaria, 1981-1987
PhD, Clinical Molecular Genetics, University of Sofia-Medical Academy of Sofia, Bulgaria, 1987-1991
Assitant Professor, Department of Medicine
Research and Clinical Interests
The main focus of my laboratory is to study the molecular mechanisms of HIV-1 entry into the brain. The molecular mechanisms of HIV-1 entry into the CNS remain enigmatic. A major possibility is via direct infection of brain microvascular endothelial cells (BMVECs), which along with astrocytes represent the major consistuent of the BBB. Given that these cells lack CD4, however, the primary cellular receptor for HIV-1 had been a major mystery. We have recently discovered that cell-associated proteoglycans (PGs) act as the primary receptors for HIV-1 on BMVECs. Our most recent data also indicate that PGs are implicated in viral attachment and entry into brain astrocytes. Itâ€™s also shown that unspecified PGs interact with HIV-1 Tat and gp1120, and we recently identified that perlecan, a specific PG class, mediates cellular uptake of Tat through a pathway responsible for biological activity. Our central hypothesis is that, distinct cell-associated PGs play differential role(s) in viral capture and transfer, via BMVECs and astrocytes. As well, PGs may be required for interactions of viral proteins (i.e. HIV-1 Tat, and gp120) with the BBBand CNS-derived cells. Our main objective is to identify the molecular mechanisms of HIV-1 entry and infection of the CNS, focusing on PG-species as the primary attachment receptors, and their interactions with certain HIV-1 proteins. Our studies should provide new insights into the role of distinct CNS-PGs in HIV-1 infection of the brain, as well as interactions with specific HIV-1 proteins and will help develop new strategies for the treatment of HIV-1 infection and AIDS-associated neuronal disorders.