Biography

Specialties and research/medical interests

Cell Biology, Basic science research on Podocyte cell biology, Bone and mineral disorders, Kidney stones, Nephrotic syndrome, Osteogenesis Imperfecta, Osteoporosis

Research Summary

Biomechanical forces in hyperfiltration-mediated injury: I have focused my research on developing strategies to attenuate the progression of chronic kidney disease (CKD) mediated by hyperfiltration in children. Hyperfiltration is the main cause of early progression of CKD in children with Congenital anomalies of the kidney and urinary tract (CAKUT). There is no specific treatment, and ACE inhibitors have been ineffective in children with CAKUT. Identifying additional molecular targets for these children will be of great value to any pediatric nephrologist. The mechanism of hyperfiltration-mediated glomerular injury remains unclear. We propose that a hyperfiltration-mediated increase in biomechanical forces within the glomerulus directly injures glomerular cells, specifically podocytes. Our systematic studies on biomechanical forces using in vivo animal models and in vitro models based on cultured podocytes and isolated glomeruli support this concept. We have developed tools and techniques to study flow-induced mechanical shear stress on cultured cells and isolated glomeruli to gain insights into the interactions between fluid mechanics and cellular processes. Immunological dysregulation in idiopathic nephrotic syndrome: The immune system is believed to cause podocyte injury in idiopathic nephrotic syndrome of childhood, specifically, minimal change disease (MCD) and focal segmental glomerulosclerosis (FSGS). The role of the immune system in MCD and FSGS is indicated by our work and by others. We have demonstrated the presence and significance of Toll-like Receptors in podocytes. I collaborate with Dr. Virginia Savin and her research group at KCVAMC who have done pioneering work in FSGS. I am closely involved with the ongoing project on the role of cardiotrophin like cytokine factor-1 (CLCF-1) in the development and post-transplant recurrence of FSGS. My basic science research related to MCD and FSGS is further complemented by conducting clinical trials related to MCD and FSGS in collaboration with other pediatric nephrologists across the country. I serve as an investigator on multi-center clinical trials on nephrotic syndrome in children.