Deepak Nihalani, PhD

Description of Research Expertise

Glomerular Diseases that affect kidney function such as diabetes and hypertension are major causes of ESRD (end stage renal disease) in the United States. Glomerular dysfunction leading to proteinuria and loss of kidney function is major cause of morbidity and mortality among kidney patients. Therefore, studies aimed at understanding the molecular events leading to proteinuria are important in developing therapeutic approaches towards prevention of ESRD. I was quite fascinated by the complexity of the filtration system that is unique in its structural and protein composition. Many studies have now established that podocytes and their specialized junctions commonly known as slit diaphragm are are physical barrier that perform the filtration function of kidney. It has been my long term goal to understand the molecular organization of this filtration assembly of the kidney. The current focus of my lab is to understand the dynamic changes in the slit diaphragm proteins that are induced in response to various glomerular disorders. Recent progress in identifying proteins such as Neph1 and Nephrin localized at these junctions suggests an active role for these proteins and their complexes in molecular events that regulate the integrity of slit diaphragm. We have recently identified a novel interaction between Neph1 and the motor protein Myo1c which we propose is involved in the organization of Neph1 complex during glomerular injury. We use modern microscopic, cell culture and animal models to investigate the role of Neph1 and other slit diaphragm proteins in podocyte biology. Our studies provide data on the critical molecular events leading to podocyte effacement and podocyte recovery during an injury/recovery event. Importantly, defining these critical molecular changes and their regulation will reveal novel therapeutic approaches to both reducing glomerular injury and improving recovery from a glomerular injury.