Research
Microarray analysis of HIV-1-infected renal epithelial cells
HIV-associated nephropathy (HIVAN) is the leading cause of end stage
renal disease among HIV-infected patients. HIV infection of renal
epithelial cells is responsible for progression of renal failure in
HIVAN. We are using oligonucleotide microarrays to examine differential
gene expression in human renal epithelial cells following infection by
HIV-1 in vitro.
Using this approach, we are able to profile the expression of thousands
of cellular genes at multiple time points after infection by HIV-1. We
have identified several candidate genes that may be important in the
pathogenesis of HIVAN and we are studying the roles of these genes in
causing progressive renal failure in patients with HIVAN.
Study of the role of FAT10 in the pathogenesis of renal disease
We have determined that the ubiquitin-like protein FAT10 is one of the
most upregulated genes in renal epithelial cells after HIV-infection.
We also have shown that FAT10 is upregulated in renal epithelial cells
kidney tissue from patients with HIVAN and autosomal dominant
polycystic kidney disease. Moreover, we have found that FAT10
expression induces apoptosis in renal epithelial cells and that
blocking FAT10 expression protects renal epithelial cells against
HIV-induced apoptosis. We are studying the molecular mechanisms by
which FAT10 induces apoptosis and cell cycle dysregulation. We employ a
wide array of cutting edge molecular techniques including molecular
cloning, quantitative PCR, confocal microscopy, immunoprecipitation,
and creation and characterization of transgenic models of renal
disease.
Publications
Ross MJ, Klotman PE, Winston JA. HIV-associated nephropathy: case study and review of the literature. AIDS Patient Care and STDs 2000; 14(12): 637-45.
Ross MJ, Bruggeman LA, Wilson PW, Klotman PE. Microcyst formation and HIV-1 gene expression occur in multiple nephron segments in HIV-associated nephropathy. J Am Soc Nephrol 2001; 12(12): 2645-51.
Ross M, Klotman PE. Recent progress in HIV-associated nephropathy [review]. J Am Soc Nephrol 2002 Dec; 13(12): 2997-3004.
Kaufman L, Hayashi K, Ross MJ, Ross MD, Klotman PE. Sidekick-1 is upregulated in glomeruli in HIV-associated nephropathy. J Am Soc Nephrol 2004 Jul; 15(7): 1721-30.
Ross M, Klotman PE. HIV-associated nephropathy. AIDS 2004 May 21; 18(8): 1089-99.
Ross MJ, Martinka S, D'Agati VD, Bruggeman LA. NF-kappaB regulates Fas-mediated apoptosis in HIV-associated nephropathy. J Am Soc Nephrol 2005 Aug; 16(8): 2403-11.
Lu TC, Ross M. HIV-associated nephropathy: a brief review. Mt Sinai J Med 2005 May; 72(3): 193-9.
Schwartz EJ, Szczech LA, Ross MJ, Klotman ME, Winston JA, Klotman PE. Highly active antiretroviral therapy and the epidemic of HIV+ end-stage renal disease. J Am Soc Nephrol 2005 Aug; 16(8): 2412-20.