Kyung Lee, PhD

Dr. Kyung Lee is an Associate Professor of Medicine in the Division of Nephrology. She received her B.S. in Biochemistry at State University of New York at Binghamton and Ph.D. in Molecular Cellular Biochemical and Developmental Sciences at Icahn School of Medicine at Mount Sinai (ISMMS). She completed her postdoctoral training in autosomal dominant polycystic kidney disease at ISMMS, and has since broadened the scope of her research interest to include other areas of chronic kidney disease, such as diabetic kidney disease, focal segmental glomerulosclerosis, and immune-mediated glomerulonephritis, and renal fibrosis. She is also a co-founder of Rila Therapeutics, Inc. (est. 2021), a biotechnology company focused on renal and other organ fibrosis and complications.

Research:

The focus of our research is on the elucidation of molecular mechanisms driving the progression of chronic kidney disease (CKD), ultimately for the identification of new therapeutic targets to combat the disease progression. In joint collaboration with He laboratory, the scope of our research encompasses a wide range of molecular pathways driving CKD and kidney fibrosis, which includes diabetic kidney disease (DKD), HIV-associated nephropathy (HIVAN), focal segmental glomerulosclerosis (FSGS), and glomerulonephritis. Our current NIH-funded studies include the following projects:

1) Investigating the mechanism by which LRG1 potentiates TGF- signaling in glomerular endothelial cells to promote DKD: Using an unbiased gene expression analysis of kidney cells from mouse models of DKD, we recently identified secreted molecule LRG1 as a potent angiogenic molecule and inducer of glomerular endothelial cell injury. Our study indicates that its increased expression accompanies accelerated DKD progression in mice and humans. As an important modulator of TGF- signal transduction, LRG1 also contributes to tubulointerstitial fibrosis development in CKD. We are working towards the development of LRG1 antagonists to mitigate CKD and fibrosis development.

2) Investigating the mechanisms by which increased expression of RARRES1 in podocytes in disease promotes podocyte injury and apoptosis: we recently identified RARRES1 as a gene whose expression was negatively correlated with estimated glomerular filtration rate (eGFR) decline and associated with worsened renal outcomes in patients with primary glomerular disease, suggesting that it may be a risk gene for glomerular disease. Our study indicates that cleavage of membrane-bound RARRES1 into a soluble ligand and its subsequent endocytic uptake by neighboring podocytes and tubular cells leads to injury in DKD. We are dissecting the mechanism of RARRES1 cleavage, which is critical for the podocyte and tubular apoptosis in vivo, and assessing whether plasma and urinary RARRES1 may serve as a prognostic marker of DKD progression in diabetic patients.

3) Investigating the mechanism by which HIV Vpr protein promotes cell cycle deregulation, tubular cell death, and proliferation defects in HIV-associated kidney disease: several lines of evidence from recent epidemiological and experimental studies indicate that concurrent HIV infection and age-related comorbidities, such as diabetes mellitus, have a synergistic effect on the incidence of CKD. Among the HIV proteins, viral protein R (Vpr) is a major culprit of kidney cell injury in HIVAN. This project is aimed to dissect the molecular mechanisms by which Vpr leads to tubular cell injury and atrophy as one outcome, while promoting hyperproliferation and inducing cystic kidney phenotype in the other, using in vitro and in vivo tools.