The Division of Nephrology’s 2020 Translational Innovation grant of $50,000 has been awarded to Sanjay Jain, MD, PhD, and Tingting Li, MD, MSCI. Their project focuses on developing methods for single nucleus transcriptomic studies on archived diagnostic frozen kidney biopsy tissue from patients with pauci-immune glomerulonephritis (PIGN). WashU Nephrology’s Translational Grant program has been offered for the past five years to stimulate innovative, collaborations between a basic scientist and a clinician in the Division.
PIGN is a hallmark of ANCA (anti-neutrophil cytoplasmic antibody)-associated vasculitis (AAV) and is the most common cause of crescentic glomerulonephritis in the adults. Despite advances in treatment, a significant proportion of PIGN patients do not achieve complete or sustained remission and many remain at high risk for end-stage renal disease and death.
“Using single nucleus transcriptomics, we will redefine PIGN at a molecular level, provide novel insights into pathogenesis and transformation of cellular phenotypes and uncover diagnostic and prognostic biomarkers,” says Jain. “We hope that our methods of interrogating archived frozen biopsy using single cell technologies, which is paradigm-shifting in the field, will be broadly applicable to other diseases and tissues.”
LI, an associate professor of medicine in our division, recently earned a master’s degree in clinical investigation at WashU in 2018. “This formal training has enriched and strengthened my investigative skills and has helped me become an independent clinical investigator,” she says. Li is also the director of the Glomerular Disease/Vasculitis Clinic at WashU. This clinic not only delivers comprehensive patient care, but also fosters translational and clinical investigation in glomerular diseases and facilitates biobanking for genome-based studies.
Associate professor of medicine Jain is the director of the Kidney Translational Research Center (KTRC) at WashU. He has built a state-of-the-art biorepository of clinical data from more than 500 patients with urinary tract malformations and more than 3500 enrolled patients with other kidney diseases, and more than 200 adults with bladder diseases for researchers worldwide. Jain has further augmented the KTRC resources by banking urine specimens from more than 200 patients with COVID-19 to study its effects on the kidneys. “Dr. Li and I have devised our proposal by bringing our complementary expertise to tackle the challenges of interrogating clinical biopsy samples and a debilitating autoimmune kidney disease, pauci-immune glomerulonephritis.”
To date, there are no reliable biomarkers that predict therapy response, relapse, or clinical outcomes for patients with PIGN . If Jain and Li’s proof-of-concept studies are successful, it will provide critical insights into the immunopathogenesis of PIGN and could pave the way for translational studies that will have broad implications in diagnosis, outcome prediction, and targeted therapies for this disease.