Research in my laboratory centers on understanding the cellular and molecular mechanisms of tissue inflammation and injury, including the kidney, lung, and vasculature, in the pathogenesis of acute and chronic diseases. Our work has focused on examining the mechanisms of signal transduction by Transforming Growth Factor-beta1 (TGF-β1), a pleiotropic cytokine and key mediator of tissue injury response and kidney fibrosis. We have extensively examined how TGF-β1 effects are mediated by the distinct TGF-β receptors via activation of intracellular signaling molecules downstream to the receptors in a cell-specific manner to regulate cellular responses in renal cells.
Our investigations have included (1) cloning and characterization of the cell surface receptors, and identification of novel interacting proteins that are involved in TGF-β1 signal transduction, (2) delineating the downstream intracellular signal transducing pathways that mediate TGF-β1 signals, in particular, the role of the mitogen-activated protein kinase (MAPK) pathways, and (3) the cellular and molecular regulation of TGF-β1 induction of cytoprotectants, such as heme oxygenase-1 (HO-1) and carbon monoxide (CO).
We are currently investigating novel mechanisms of regulation and function of autophagy, inflammasomes, and necroptosis in models of organ injury, including the kidney, lung, and heart. In collaboration with laboratories at Weill Cornell Medical College, we are also studying mechanisms of multi organ injury in sepsis, acute and chronic lung injury (Dr. Augustine Choi, Chairman, Weill Department of Medicine and Professor, Division of Pulmonary & Critical Care Medicine), HIV/antiretroviral therapy related cardiac/kidney fibrosis (Dr. Jeffrey Laurence, Professor of Medicine, Division of Hematology & Medical Oncology), and juvenile chronic kidney disease (Dr. Oleh Akchurin, Assistant Professor of Pediatrics, Division of Pediatric Nephrology). The ultimate goal of our research is to identify novel therapeutic targets that will provide cytoprotection against tissue injury such as progressive kidney diseases.