Here is a summary of the research works occurring in our laboratory, as we study Kidney Podocyte Injury in Glomerular Disease.
- Systems biology approach to study HIV-associated kidney disease: We found that HIV Nef induces Src-Stat3, Ras-cRAf-MAPK, and Rac1-PAK pathways leading to proliferation, dedifferentiation, and changes of the cytoskeletal structure in podocytes.
We are investigating the relationship between Nef-induced signaling pathways and the downstream transcription factor and gene activation in HIV-1 transgenic mice using systems biology approach. We are using genomic-wide promoter analysis and Gene2network analysis for protein-protein interaction.
Several key transcription factors and its target genes have been identified to play key roles in the pathogenesis and progression of HIV-associated kidney disease. We are further studying the role of these transcription factors or genes using knockout approach.
- Pathogenesis of glomerulosclerosis in diabetic nephropathy: We found that AGE causes podocyte apoptosis via activation of distinct intracellular pathways and transcription factors. We are investigating the role of Sirt1-FOXO4 in diabetic nephropathy.
- Effects of retinoic acid and its retinoic acid receptors in kidney disease: We found that retinoid acid can reverse abnormal phenotype in disease podocytes including podocytes infected with HIV or under high glucose treatment. Retinoic acid stimulates intracellular cAMP production and activates CREB transcription factor, leading to podocyte differentiation through binding to RARalpha.
We are further studying the role of RARalpha using transgenic and knockout approaches. The specific agonist for RARalpha has been tested to treat HIV-associated kidney disease and diabetic nephropathy. We are also investigating the metabolism of retinoids in normal and disease kidneys.
- Establish an in vitro model of glomerular filtration unit using nanotechnology, computational modeling, and high resolution in vivo image studies. The relationships between the morphology of podocyte foot process, cell signaling, and function, will be studied. The interaction between podocytes, GBM, and endothelial cells will be also investigated.
- Using systems biology approach, we identify HIPK2 as a key signaling molecule mediating TGF-beta signaling and kidney fibrosis. We are investigating the role of HIPK2 in epithelial-mesenchymal transformation in renal tubular epithelial cells.
Icahn Research Building
1425 Madison Avenue
12th Floor, Room 12-76 (Lab)
New York, NY 10029