Dr. Falguni Das

Dr. Falguni Das
Department of Medicine, Division of Nephrology, University of Texas Health Science Center at San Antonio (UTHSCSA), United States
 
Biography
Department of Medicine, Division of Nephrology, University of Texas Health Science Center at San Antonio (UTHSCSA)
 
Research Interest
My research focuses on understanding the cellular and molecular mechanisms of different types of kidney disease and to identify the signaling pathways that regulate kidney disease. Understanding the components in these signaling pathways and their mechanisms of action is key for developing therapeutic approaches that will improve kidney function. After joining the laboratory of Dr. Goutam Ghosh Choudhury, I took up a new challenge of investigating the molecular signaling mechanism of transforming growth factor beta (TGF-?) in chronic kidney disease (CKD). We discovered a novel signaling mechanism whereby TGF? plays a role in CKD. We showed that TGF? acts through two important enzymes, phosphatidylinositol 3?kinase (PI3K) and Akt which leads to expression of a gene called plasminogen activator inhibitor-1 (PAI-1). For the first time our data demonstrated a novel mechanism of PAI-1 gene expression in response to TGF?, which plays a pathologic role in kidney damage.These unique studies have provided new insights into the pathogenesis of kidney fibrosis and possible therapeutic option for prevention and treatment of chronic kidney disease. This significant work was published in the highly reputable biomedical journal Journal of Cellular Physiology (Das F et al .214:513-527, 2008). My study also investigated the pathophysiology of diabetic nephropathy. We discovered a novel molecular pathway underlying diabetic nephropathy. We demonstrated that Rictor, a novel binding partner of the signaling molecule mammalian target of rapamycin complex (mTOR), negatively regulates TORC1 activity to control basal protein synthesis, thus conferring tight control on cellular hypertrophy, which is one of the pathological features of diabetic nephropathy. This study provided a better understanding of the molecular mechanism involved in the diabetic kidney. This innovative and important work published in the prestigious journal Cellular Signaling (Das F et al 20:409-423, 2008). We discovered a preventive role of TGF? in proliferative signaling pathway of another growth factor, platelet-derived growth factor (PDGF), which plays important role in the development of mesangioproliferative glomerulonephritis of kidney (Das F et al FEBS Letter 581: 5259-5267,2007). I demonstrated the first evidence that TGF?-stimulated a protein called p90RSK (p90 ribosomal S6 kinase), which plays an important role in cell growth by activating several transcription factors, and contributes to mesangial cell protein synthesis and hypertrophy. (Das F et al. FEBS Letter 2010). I made a potentially major scientific breakthrough in understanding and treating kidney disease that is associated with diabetes. We discovered novel roles of a cancer promoting protein called DJ-1 and a tumor suppressor protein called PTEN in diabetic kidney disease. We demonstrated for the first time the elevated levels of DJ-1 protein in diabetic conditions. Our outstanding research finding for the first time linked a protein, which is absent in Parkinson?s disease, to the pathologic features of diabetic kidney disease and the novel protein DJ-1 may represent a therapeutic target for the prevention of diabetic kidney disease. This important work provided potential new avenues for preventing the development and progression of diabetic nephropathy (Das F et al., Cellular Signaling, 23: 1311-1319, 2011). For the first time we demonstrated a novel signal transduction mechanism for the expression of PTEN, which contributes to renal pathology in many diseases including diabetes, cancer and TSC. These original high quality studies were published recently in highly reputed prestigious journal JBC (Das F et al., 287(6)3808-22.2012). Recently, We showed a novel mTOR interacting protein called Deptor which functions as an endogenous inhibitor of the kinase activity for both TORC1 and TORC2 may be amenable for rational drug designing to increase its expression that may ameliorate renal disease such as diabetic nephropathy where mesangial cell hypertrophy plays a pathologic role. (Das F et al., JBC, 15; 288(11):7756-68. 2013)