The M. Chen Lab
Primary nephrotic syndrome (NS) is characterized by heavy proteinuria, hypoalbuminemia and increased risk of loss of kidney function. It causes serious morbidity and high mortality, accounting for ~15% of prevalent end-stage renal disease at an annual cost of more than $3 billion in the US. There is no effective treatment for most cases of NS caused by genetic mutations.
Our research centers on investigating the role of podocyte endoplasmic reticulum (ER) stress in NS caused by podocyte gene mutations. This focus integrates three major themes. First, we aim to define molecular mechanisms underlying genetic determinants of NS by utilizing a combination of stably transfected cell lines, transgenic and knock-out animal models, and next generation sequencing data and biospecimens, including blood, urine and induced pluripotent stem cells, derived from human NS patients. Second, we discover and validate podocyte ER stress biomarkers in human NS patients. Finally, we identify ER stress modulators by employing high throughput drug screening. Ultimately, we hope to develop highly-targeted clinical trials to treat NS patients.
We are also interested in dissecting the role of endothelial cells (ECs) in glomerulosclerosis and renal interstitial fibrosis with an emphasis on a vascular growth factor angiopoietin-1 (Ang-1) and its receptor Tie2 in kidney. Ang-1/Tie2 signaling is pivotal in regulating blood vessel development and modulating vascular response to injury. We are using cutting-edge research approaches to investigate the cross-talk between ECs and podocytes or between ECs and pericytes, respectively.