Paul Klotman Laboratory

The Paul Klotman laboratory studies HIV-associated nephropathy (HIVAN) and how the kidney responds to HIV infection. HIVAN only afflicts people of African descent, and remains a leading cause of renal disease in the African American community. Additionally, as highly active anti-retroviral therapy (HAART) is introduced to Africa, HIVAN represents a potential epidemic of renal disease.

Previous work by our group definitively established that HIV can cause kidney disease through direct infection of the renal epithelium. We found that the kidney is a reservoir for replicating virus distinct from peripheral blood. Additionally, we have elucidated how HIV disrupts signalling networks within the key filtration cells of the kidney, and how this leads to renal infection.

We also discovered Podocan, an upregulated gene in the setting of HIVAN. Podocan belongs to the small leucine-rich repeat proteins (SLRP), a group of extracellular matrix genes which regulate growth, fibrogenesis and wound healing. We are currently studying the role Podocan plays in mediating HIVAN and other related diseases. Given the importance of other SLRPs in a broad spectrum of diseases, we are also investigating the roles of Podocan in bone and cardiovascular diseases.

Another topic we are investigating is the role of myosin, heavy chain 9 (MYH9) in kidney disease. MYH9 deficiency is known to cause kidney disease, and recent work by other groups has shown that MYH9 genetic variation may explain the African predisposition to HIVAN and other related forms of kidney disease. Our group is actively exploring what role MYH9 has in mediating the pathogenesis of HIVAN, as well as MYH9’s role in maintaining normal kidney function.