Description of Clinical Expertise

My clinical interest is in human glomerular disease including specific entities such as focal segmental glomerulosclerosis, membranous nephropathy, ANCA vasculitis and lupus nephritis. I am one of three clinical supervisors that precept fellows in the busy nephrology clinic located in the Center for Advanced Medicine. Within this practice, referrals from other nephrologists in the NY metropolitan are seen where we manage complex glomerular disease including steroid resistant FSGS, IgA Nephropathy, relapsing minimal change disease and double positive/overlap syndromes. To advance the care we provide to patients with glomerular disease I have supervised and directly participated in several initiatives. First, a framework for making novel therapeutic approaches like Rituximab available directly to our patients has been developed. Second, we have opened the door to clinical trial participation for these rare disorders. Another is in development for lupus nephritis. Finally, I direct a Glomerular Disease Biorepository that has so far enrolled 300 patients. Here, the use of banked blood, urine and tissue at the time of kidney biopsy provides an opportunity for personalized therapeutic approaches to human glomerular disease.

Description of Research Expertise

I am a physician scientist working to characterize novel pathways in kidney podocyte injury and survival. Our goal is to advance the understanding of the underlying mechanism of glomerular disease progression while identifying potential targets for therapeutic intervention. We have identified the novel pro-injury signaling molecule dendrin as a key mediator of podocyte injury. We found that dendrin ablation delayed the onset and severity of proteinuria, renal failure, podocyte loss and most importantly, improved survival in a rodent model of progressive focal segmental glomerulosclerosis (FSGS). Additionally, we found that the Hippo signaling pathway Yes-Associated Protein (YAP) is an inhibitor of dendrin pro-injury function. We recently demonstrated that podocyte-specific deletion of YAP results in an FSGS phenotype analogous to human disease. These findings are significant as they establish dendrin as a potential therapeutic target in treating proteinuric disease and open the door to further definition of the role of the Hippo signaling pathway in podocyte hemeostasis. Our current research focus centers on determining the role of dendrin in glomerular cell crosstalk and disease progression while developing a pharmacologic strategy for dendrin inhibition. In parallel our group will continue to define the role of the Hippo pathway in podocytes under normal and disease conditions in an effort consistent with our goals of enhancing the therapeutic pipeline in this clinical area where no cell-specific therapy is currently clinically available.