Sherwin Ng

Program: Molecular Cell Biology

Current advisor: Stacey L. Rentschler, MD, PhD

Undergraduate university: Cornell University, 2017

Enrollment year: 2019

Research summary
Effects of ionizing radiation on cardiac electrophysiology

We are studying the anti-arrhythmic mechanisms of cardiac radiotherapy using a combination of electrophysiological and molecular approaches. To establish efficacy of murine cardiac irradiation, we used in vivo programmed electrical stimulation and demonstrated decreased ventricular arrhythmia inducibility and reduced arrhythmia severity in mice treated with 15 and 25 Gray (Gy) compared to sham controls. Furthermore, 25 Gy irradiation increased ejection fraction six weeks post-RT compared to baseline, with no significant changes to end diastolic volume. Given these changes to cardiac function and electrophysiology, we next identified transcriptomic changes in the left ventricle six weeks after 25 Gy radiation using single nucleus-RNA sequencing. Notably, KEGG pathway analysis of upregulated genes identified ‘axonal guidance’ as the top pathway in irradiated cardiomyocytes. Genes in this pathway included semaphorin3a as well as members of the Slit/Robo family, both of which mediate axon repulsion. Consequently, Western blot showed decreased expression of tyrosine hydroxylase at the scar border zone of irradiated mice. Consistent with homogenized sympathetic innervation, optical mapping revealed changes in repolarization and potassium channel expression. These findings suggest a novel role for radiation-induced remodeling of the sympathetic nervous system in the anti-arrhythmic response to SBRT.

Graduate publications
Brumback BD, Dmytrenko O, Robinson AN, Bailey AL, Ma P, Liu J, Hicks SC, Ng S, Li G, Zhang DM, Lipovsky CE, Lin CY, Diamond MS, Lavine K, Rentschler SL. 2023 Human Cardiac Pericytes are Susceptible to SARS-CoV-2 Infection. JACC Basic Transl Sci, 8(2):109-120. PMCID: PMC9473702

Pedersen LN, Valenzuela Ripoll C, Ozcan M, Guo Z, Lotfinaghsh A, Zhang S, Ng S, Weinheimer C, Nigro J, Kovacs A, Diab A, Klaas A, Grogan F, Cho Y, Ataran A, Luehmann H, Heck A, Kolb K, Strong L, Navara R, Walls GM, Hugo G, Samson P, Cooper D, Reynoso FJ, Schwarz JK, Moore K, Lavine K, Rentschler SL, Liu Y, Woodard PK, Robinson C, Cuculich PS, Bergom C, Javaheri A. 2023 Cardiac radiation improves ventricular function in mice and humans with cardiomyopathy. Med (N Y), 4(12):928-943.e5. PMCID: PMC10994563