David Zhang

Program: Molecular Cell Biology

Current advisor: Stacey L. Rentschler, MD, PhD

Undergraduate university: University of Pennsylvania

Research summary
I am conducting my thesis research in the lab of Dr. Stacey Rentschler to explore the electrophysiologic and molecular effects of high-dose, single fraction radiation to the adult mammalian heart. Ventricular tachycardia (VT) is a dangerous arrhythmia that leads to sudden cardiac arrest and death if left untreated. VT most often occurs in regions of the diseased heart that are structurally and/or electrically heterogeneous and predispose to electrical reentry. Current available antiarrhythmic and catheter ablation therapies are limited. In patients with VT that is refractory to conventional therapy, radiation therapy (RT) has emerged as a promising new treatment. Although the reduction in in VT burden after cardiac RT has now been replicated at several hospitals, the mechanism of radiation-induced VT reduction remains unclear. My research centers around the hypothesis that ionizing radiation to the mammalian heart leads to cardiomyocyte reprogramming. I seek to characterize key physiologic and molecular mechanisms by which ionizing radiation influences cardiac biology. I am implementing a number of techniques ranging from optical mapping of Langendorff-perfused hearts or human organotypic cardiac slices to cardiomyocyte nuclei isolation and next-generation sequencing to determine whether ionizing radiation to the heart causes permanent, epigenetic reprogramming of the heart to prevent drug- and ablation-refractory arrhythmias.

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. 2022 Human Cardiac Pericytes are Susceptible to SARS-CoV-2 Infection. JACC Basic Transl Sci, (Epub ahead of print):.

Li G, Brumback BD, Huang L, Zhang DM, Yin T, Lipovsky CE, Hicks SC, Jimenez J, Boyle PM, Rentschler SL. 2022 Acute Glycogen Synthase Kinase-3 Inhibition Modulates Human Cardiac Conduction. JACC Basic Transl Sci, 7(10):1001-1017.

Zhang DM, Szymanski J, Bergom C, Cuculich PS, Robinson CG, Schwarz JK, Rentschler SL. 2021 Leveraging Radiobiology for Arrhythmia Management: A New Treatment Paradigm?. Clin Oncol (R Coll Radiol), 33(11):723-734.

Zhang DM, Navara R, Yin T, Szymanski J, Goldsztejn U, Kenkel C, Lang A, Mpoy C, Lipovsky CE, Qiao Y, Hicks S, Li G, Moore KMS, Bergom C, Rogers BE, Robinson CG, Cuculich PS, Schwarz JK, Rentschler SL. 2021 Cardiac radiotherapy induces electrical conduction reprogramming in the absence of transmural fibrosis. Nat Commun, 12(1):5558.

Lipovsky CE, Jimenez J, Guo Q, Li G, Yin T, Hicks S, Bhatnagar S, Takahashi K, Zhang DM, Brumback BD, Goldsztejn U, Nadadur RD, Perez-Cervantes C, Moskowitz IP, Liu S, Zhang B, Rentschler SL. 2020 Chamber-specific transcriptional responses in atrial fibrillation. JCI Insight, 5(18):e135319.