Physician-Scientist Ying Maggie Chen Receives VA Merit Award

Congratulations to Associate Professor of Medicine, Ying Maggie Chen, MD, PhD, WashU Nephrology, who received a four-year, $1.15M VA Merit Award from the U.S. Department of Veterans Affairs.  The funding will support her research on therapeutic targeting of mitochondria in uromodulin-associated chronic kidney disease (CKD). 

The $1.15M grant award includes the $750,000 grant (direct costs) plus $399,000 for the principal investigator’s research time.  The VA Merit Award is equivalent to an R01 grant from the National Institutes of Health.

A physician-scientist, Dr. Chen is a nephrotic syndrome (NS) specialist who treats rare, protein-spilling kidney diseases.  She is the Director of WashU Nephrology’s Nephrotic Syndrome Clinic. 

A major focus of the M. Chen Laboratory is investigating the molecular pathogenesis of organelle dysfunction-induced kidney diseases, to discover endoplasmic reticulum (ER) stress biomarkers, and to develop highly-targeted therapies by employing high-throughput drug screening.  Her group has pioneered discovery of urinary ER stress biomarkers, including MANF, CRELD2 and BiP (Patent 10156564, 2018).  They have also discovered a new class of drugs, podocyte ER calcium stabilizers in the treatment of NS, and are currently leading the investigation of the function of the novel ER protein MANF in the treatment of kidney disease.

The current study focuses on uromodulin (UMOD)-associated chronic kidney disease (CKD), or autosomal dominant tubulointerstitial kidney disease caused by UMOD mutations (ADTKD-UMOD), which is characterized by progressive renal fibrosis and CKD.  Currently, there is no targeted therapy.  Frequently, the disease is not manifested until adulthood and its prevalence has been significantly underestimated in Veterans and the general population. 

The VA Merit Award will help fund the development of novel therapies to restore mitochondrial function and alleviate mitochondria-mediated inflammation in ADTKD. The study will provide critical insights into the molecular pathogenesis of ADTKD and other forms of organelle stress-induced CKD, as well as discover mitochondria-targeted and mechanism-based novel treatments for ADTKD and CKD in Veterans.

“Getting this grant is a collective effort from multiple members in our lab, including the previous lab manager Yeawon Kim, and three outstanding postdocs, Chuang, Chenjian and Yili.  This grant will provide important monetary resources to catalyze our research effort in ADTKD, for which we have established an ADTKD Clinic.
Through close collaboration with NIH/NCATS, investigators in other academic institutions and patient organizations, we hope to advance to investigator-initiated clinical trials in the future based on the drug targets we have identified.”

Ying Maggie Chen