Mary Klotman, MD is the chair of the Department of Medicine at Duke University Medical Center. The Klotman laboratory joined the Duke Human Vaccine Institute in December 2010. The laboratory includes Andrea Cara, Donatella Negri, and Bala.
The primary focus of Dr. Klotman’s research efforts is understanding fundamental host-viral interactions that provide insights into pathogenesis and approaches to prevention of Human Immunodeficiency Virus 1 (HIV-1) infection. A long-standing project is focused on HIV-associated nephropathy (HIVAN) as part of a multi-project NIH-funded initiative to understand the cell biology, virology and genetically determined host factors involved in disease pathogenesis. Recent important observations made by the Klotman lab include the demonstration that HIV resides in and evolves separately in kidney cells, that virus persists in renal cells despite therapy, and the viral proteins Nef and Vpr play significant roles in renal pathology. Current work is focused on defining the efficiency and consequences of cell-associated (compared to cell-free) HIV infection of renal tubule epithelial (RTE) cells via the virologic synapse; defining the mechanism by which specific viral genes, particularly HIV Vpr, induce pathologic changes in RTECs that are characteristic of HIVAN and characterization of the renal compartment as a long-term reservoir for HIV.
An additional focus in the laboratory is understanding the role of the genital mucosa and associated host proteins that protect or, in the context of a second sexually transmitted disease, might enhance HIV transmission. Ultimately, the goal of the latter work is to devise safe strategies for prevention, particularly around topical microbicides that might be applied directly to the genital mucosa to block sexual transmission. This work is presently focused on establishing in vitro models to study vaginal transmission and topical microbicides including genital cell monolayers and genital tissue explant models.