Congratulations to Ying Maggie Chen, MD, PhD, FASN, who is featured in the September issue of the Division of Physician-Scientists (DPS) newsletter.
Dr. Chen is a physician-scientist specializing in nephrotic syndrome and rare, protein-spilling kidney diseases and autosomal dominant tubulointerstitial kidney disease (ADTKD). She serves as Associate Professor in both the Division of Nephrology and the Department of Cell Biology & Physiology at Washington University. In addition, she directs the Autosomal Dominant Tubulointerstitial Kidney Disease Center and the Nephrotic Syndrome Clinic at WashU Nephrology.
The following interview with Dr. Chen is excerpted from the September DPS Newsletter:
What motivated you to become a physician-scientist?
I feel passionate about developing novel therapeutics for kidney disease, especially for monogenic kidney disease. I am also fascinated with organelles, including endoplasmic reticulum (ER), mitochondria and lysosome. Thus, it is motivating to me to discover non-canonical functions of novel ER stress-inducible proteins, which could be great candidates for drug targets.
Tell us about your research
My research focus is regulation and therapeutic manipulation of organelles in kidney disease. My research spans from basic biology to translational study to future investigator-initiated clinical trials based on novel drug targets identified in our cell, mouse and patient hiPSC-differentiated kidney organoid models. We have been studying various kidney diseases triggered by endoplasmic reticulum (ER) dysfunction, including primary nephrotic syndrome (NS) caused by podocyte ER stress, autosomal dominant tubulointerstitial kidney disease (ADTKD), a prototypical protein misfolding disease resulting from mutant protein aggregates in the ER, and acute ischemic kidney injury intensified by ER calcium depletion.
We have pioneered discovery of urinary ER stress biomarkers, including mesencephalic astrocyte–derived neurotrophic factor (MANF), cysteine-rich with EGF-like domains 2 (CRELD2) and BiP in the kidney disease. In addition, we have discovered podocyte ER calcium stabilizers as a new class of drugs to treat NS. Recently, we have identified thioredoxin interacacting protein (TXNIP) as an important drug target to control ER-mitochondria crosstalk in NS, and MANF as a biotherapeutic protein to stimulate autophagy for the treatment of ADTKD.
What is the future plan of your research?
I will continue delving deep into ER-mediated organelle cross talk in kidney disease to identify novel therapeutic targets. Introduced by Dr. Fumi Urano, my long-term collaborator and one of my great mentors, I have been working closely with a group of resourceful investigators at NIH/NCATS who are experienced in drug discovery. My goal is to develop novel chemical compounds and therapeutic peptides conjugated with unique cell penetrating peptide (CPP), file composition patents and get FDA Investigational New Drug (IND) approval for conducting clinical trials. I have been very interested in RNA-based therapy for a couple of years, but was unable to move forward. I am recently approached by a leading RNAi company and look forward to productive collaboration with industry.
With support from our Division, I have established an ADTKD Center and NS Clinic to assemble genotyped patient cohorts to prepare for future clinical trials. We will continue working with patient organizations, including NephCure and Rare Kidney Disease Foundation, to push the field forward.
