(1) Podocyte biology and pathology: a. We are studying the effects of retinoic acid, retinoic acid receptors, and their downstream signaling pathways in podocyte differentiation and glomerular disease. We are studying the therapeutic effects of specific agonists of retinoic acid receptors in HIV-associated kidney disease and diabetic nephropathy. We are also investigating the role of retinoic acid in podocyte regeneration. b. We are studying the role of Sirt1, acetylation of transcription factors, and bromodomain inhibitors in podocyte injury and glomerular diseases. (2) Systems biology approach to study signaling networks in kidney disease: a. Using a systems biology approach, we identify HIPK2 as a key signaling molecule mediating TGF-βa signaling and kidney fibrosis. We are investigating the role of HIPK2 in renal fibrosis. b. We are analyzing gene expression and proteomic profiles in glomeruli of animal models of kidney disease and trying to identify new biomarkers and drug targets for the treatment of kidney disease. c. We have applied the Connectivity Map (CMAP) database developed at the Broad Institute to prioritize pairs of drugs that can potentially and optimally reverse the gene expression changes observed in diseased kidneys. We are using this approach to develop new combination therapy for kidney disease.