R56 NIH Grant Awarded to Physician-Scientist Ying Maggie Chen

Congratulations to Ying Maggie Chen, MD, PhD, Associate Professor, WashU Nephrology, on receiving an R56 grant from the National Institutes of Health (NIH)/National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) to study impaired autophagy underlying the disease pathogenesis of autosomal dominant tubulointerstitial kidney disease (ADTKD).

Dr. Chen is a nephrotic syndrome specialist who treats rare, protein-spilling kidney diseases.  A physician scientist, she is the director of both the Autosomal Dominant Tubulointerstitial Kidney Disease Clinic and the Nephrotic Syndrome Clinic at WashU Nephrology as well as head of the Y. Maggie Chen Lab.

ADTKD caused by uromodulin mutations (ADTKD-UMOD) is one of the most common hereditary kidney diseases.  It represents as many as 25% of patients with inherited kidney disease, after exclusion of polycystic kidney disease and Alport syndrome.  ADTKD is characterized by progressive renal fibrosis, and currently there is no treatment.

Using CRISPR/Cas9 to develop targeted therapies, Dr. Chen’s laboratory generated the first ADTKD-UMOD mouse model harboring a leading human UMOD deletion mutation.  UMOD is largely synthesized and secreted by tubular cells of thick ascending limb (TAL).  Chen’s mouse model shows that autophagy deficiency in TALs leads to increased accumulation of mutant UMOD protein-the root cause of the disease, eventually causing TAL cell death and renal fibrosis in ADTKD.

“The goal of this R56 award is to delineate the molecular mechanism regulating autophagy in ADTKD. The proposed study will pave the way to develop new therapeutic strategies for ADTKD patients, with a specific focus on the autophagy receptor p62.”

Ying Maggie Chen