Ying Maggie Chen, MD, PhD, FASN, Associate Professor of Medicine in the Division of Nephrology, has been awarded a National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) R01 grant totaling $2.969 million for her project, “Activating Autophagy to Treat Uromodulin-Associated Genetic Chronic Kidney Disease.”
Autosomal dominant tubulointerstitial kidney disease caused by uromodulin mutations (ADTKD‑UMOD) is one of the leading hereditary kidney diseases, marked by renal fibrosis and progressive loss of kidney function. Despite its impact, there are currently no targeted therapies for patients with this condition.
To address this critical gap, Dr. Chen’s team developed a novel CRISPR/Cas9‑engineered mouse model carrying the Umod p.Tyr178‑Arg186 deletion – the mouse equivalent of the most common human UMOD mutation. Their work has shown that mutant uromodulin triggers endoplasmic reticulum (ER) stress and disrupts autophagy and mitophagy in thick ascending limb (TAL) cells. This deficiency leads to the accumulation of toxic UMOD aggregates, TAL cell death, and ultimately renal fibrosis (see manuscript in Nature Communications, 2023).
The newly funded project aims to develop autophagy‑activating therapies as a highly targeted treatment strategy for ADTKD‑UMOD, offering new hope for patients with this currently untreatable genetic kidney disease.
Dr. Chen leads the ADTKD Center, established at WashU Nephrology in 2024, which offers personalized clinical management alongside state-of-the-art molecular phenotyping technology to identify novel drug targets and validate emerging biomarkers. The clinic works closely with patients, patient organizations, pharmaceutical companies, and international ADTKD consortia to identify the optimal treatment for ADTKD.
“The R01 funding will further catalyze our research and deepen the impact we can have for patients through our ADTKD Center.”
Ying Maggie Chen
In addition to this major grant, Dr. Chen has been invited to speak at the Center for Drug Discovery’s 10‑Year Anniversary Scientific Symposium next week, March 25, 2026. Her talk, “Developing Molecular Therapeutics for Genetic Kidney Disease,” will highlight her team’s translational efforts to advance precision therapies for inherited kidney disorders.
The symposium celebrates a decade of discoveries, collaborations, and therapeutic innovations made possible through CDD‑supported research, and Dr. Chen’s work exemplifies the center’s mission to accelerate the development of novel treatments.
For details and registration for the CDD 10‑Year Anniversary Symposium, visit the symposium website. See itinerary below.
