Won-Kyung Cho, MD

Assistant Professor of Medicine at the Warren Alpert Medical School of Brown University
Providence VA Medical Center

830 Chalkstone Ave.
Building 35, room 208
Providence, RI 02908

Email: won-kyung_cho@brown.edu

Won-Kyung Cho, MD

Bio

Won-Kyung Cho, MD is currently an Assistant Professor of Medicine at the Alpert Medical School of Brown University and staff pulmonary/critical care physician at the Providence VA Medical Center.

After completing her clinical training as a Pulmonary Critical Care physician in South Korea, she went to Canada to obtain research experience at McGill University and also studied at the University of Pittsburgh Medical Center. Thereafter she returned to South Korea to become an Assistant Professor at her alma mater, Ewha Womans University, but returned to the U.S. to restart her career as a physician scientist. She completed her second residency training in internal medicine at St. Mary’s Health Center in St. Louis and went to Yale University for fellowship in pulmonary/critical care/sleep medicine. After completing her fellowship, she continued to stay at Yale as an Associate Research Scientist to get further research training until she was appointed Instructor in Internal Medicine in the Pulmonary/Critical Care/Sleep Medicine Section at Yale in 2013. Then she moved to Brown University in 2015 with her recently funded K08 award from NHLBI.

Her research interest lies in understanding the important interplay between immune process and pulmonary vascular remodeling/pulmonary arterial hypertension (PAH). Thus far, the underlying mechanism of PAH has not been clearly understood. Her previous studies demonstrated that when IL-13 is chronically overexpressed in murine lungs using a transgenic approach, the mice develop significant vascular remodeling leading to pulmonary hypertension. Her previous work has opened up new opportunities and research avenues in the mitochondrial/metabolic field (the Warburg effect in noncancerous cells and the Randle cycle). Thus, she has expanded her research interest to study the interplay between immune and metabolic processes in the pathogenesis of PAH.

COBRE Abstract

Pulmonary arterial hypertension (PAH) is a lethal disease caused by elevated vascular resistance due to lumen obliterating processes in small pulmonary arteries. Recent studies including ours have implicated a key role for interleukin-13 (IL-13), a T helper type 2-cell (Th2) effector cytokine, in the pathogenesis of PAH. Our recently published findings in rodent models have corroborated these findings: 1) we found that IL-13 transgenic mice (IL-13 tg mice) develop significant pulmonary vascular remodeling and pulmonary hypertension (PH); 2) this was at least in part due to increased proliferation of pulmonary artery smooth muscle cells (PASMCs); and 3) we identified IL-13 receptor α2 (IL-13Rα2) and Arginase2 (Arg2), the mitochondrial isozyme that breaks down L-Arginine, as key modulators of the IL-13 effect on pulmonary vascular remodeling. Recently, increased fatty acid beta-oxidation that might lead to decreased glucose oxidation via the mutually inhibitory balance between two metabolic pathways (the Randle cycle), has been implicated to play a key role in the generation of proliferative phenotype in PH cells. In our preliminary studies, we observed that inhibition of fatty acid beta-oxidation by giving Ranolazine Dihydrochloride via drinking water (30mg/250ml) for one month significantly attenuated not only lung inflammation but also the PH phenotype of right ventricle (RV) of IL-13 tg mice (N=3 in each group). Based on these findings, we hypothesize that the development of tissue and cellular inflammatory responses by IL-13, including IL-13-induced pulmonary vascular phenotype, requires fatty acid beta-oxidation. To address this, we will do the following. First, we will do the same animal experiments using a large group of animals. Then remodeling assessment of pulmonary arteries and right ventricle (RV) as well as measurement of RV systolic pressure by performing right heart catheterization will be done. Second, we will determine the roles of fatty acid metabolism in the regulation of IL-13-specific effects on PASMCs, cardiac myocytes and inflammatory cells. Lastly, we will investigate the roles of the IL-13Rα2 – Arg2 axis in the regulation of fatty acid metabolism by IL-13 using Arg2 and IL-13Rα2 null mutant mice as well as PASMCs and cardiac myocytes transfected with the specific siRNA of Arg2 or IL-13Rα2.

Publications
Project Updates
Mentors

Mentor:
Dr. Sharon Rounds, MD
Professor of Medicine and of Pathology and Laboratory Medicine at the Alpert Medical School of Brown University