Research in the Zhao Wang Lab centers on cardiovascular disease, a condition that is not fully understood despite being the leading cause of death worldwide, including among diabetes and hypertension patients. Additionally, cancer treatment with chemotherapy, radiation or targeted drugs can have side effects that lead to heart disease. We explore the underlying cellular and molecular mechanisms that cause changes to the heart seen in cardiovascular disease and its treatment, including those involving metabolism, stress and signals sent out by fat cells. Our ultimate goal is to apply the knowledge we discover to develop new prevention strategies for heart failure — and, one day, a cure.
The Zhao Wang Lab focuses on pathological cardiac remodeling due to cardiac hypertrophy, heart failure, cancer treatment, myocardial infarction, senescence and diabetes. We use approaches that span biomedical disciplines, integrating genetics in lab models, tissue culture, imaging and multi-omics. Our work has yielded exciting insights into the roles of myocardial metabolism, the unfolded protein response (UPR), the integrated stress response (ISR), translation regulation and adipokines.
Ischemic heart disease is common in both developed and developing countries. The main treatment, reperfusion of a blocked coronary artery, can cause additional damage, accounting for up to 40 percent of the final infarct size — an important predictor of patient outcomes. We have found that the UPR and the ISR are potently activated by heart attack and reperfusion treatment, and showed that these adaptive pathways protect the heart.
Enlargement of the heart can occur as a protective response to high blood pressure. Unfortunately, this adaptive cardiac hypertrophy may progress into heart failure. Our research has shown that the condition is driven by metabolic alterations and protein folding in a process with two-way traffic. We now focus on the role of glycolysis, hexosamine biosynthesis, the pentose phosphate pathway and the UPR in cardiac hypertrophy and heart failure under pressure overload.
Diabetes and heart disease
More than two-thirds of diabetic patients develop heart disease, the major cause of death for these patients. There are at least two reasons: Metabolic stress in obesity and diabetes may directly impair the heart, and the systemic nature of the metabolic disease may spur other tissues to send signals that interfere with the heart. To improve our understanding of diabetes-related heart disease, we investigate the role of the UPR, glucose metabolism and inter-organ crosstalk.
In addition to the well-known, life-threatening dangers of cancer, the disease and its treatment are associated with cardiac impairment. The Zhao Wang Lab aims to uncover the biochemical basis for not only cancer therapy’s toxicity to cardiomyocytes and endothelial cells but also the interplay between the cardiovascular system and tumors, with a focus on metabolism, senescence and inflammation.
Principal Investigator: Zhao Wang, Ph.D.
An Associate Professor in the Department of Diabetes Complications & Metabolism
Genetic Deletion of the LINC00520 Homolog in Mouse Aggravates Angiotensin II-Induced Hypertension
Tang, X., Lai, C. H., Malhi, N. K., Chadha, R., Luo, Y., Liu, X., Yuan, D., Tapia, A., Abdollahi, M., Zhang, G., Calandrelli, R., Shiu, Y. T., Wang, Z. V., Rhee, J. W., Zhong, S., Natarajan, R., & Chen, Z. B.
Rewiring of 3D Chromatin Topology Orchestrates Transcriptional Reprogramming and the Development of Human Dilated Cardiomyopathy
Feng Y, Cai L, Hong W, Zhang C, Tan N, Wang M, Wang C, Liu F, Wang X, Ma J, Gao C, Kumar M, Mo Y, Geng Q, Luo C, Lin Y, Chen H, Wang SY, Watson MJ, Jegga AG, Pedersen RA, Fu JD, Wang ZV, Fan GC, Sadayappan S, Wang Y, Pauklin S, Huang F, Huang W, Jiang L.
Pharmacological inhibition of arachidonate 12-lipoxygenase ameliorates myocardial ischemia-reperfusion injury in multiple species
Zhang XJ, Liu X, Hu M, Zhao GJ, Sun D, Cheng X, Xiang H, Huang YP, Tian RF, Shen LJ, Ma JP, Wang HP, Tian S, Gan S, Xu H, Liao R, Zou T, Ji YX, Zhang P, Cai J, Wang ZV, Meng G, Xu Q, Wang Y, Ma XL, Liu PP, Huang Z, Zhu L, She ZG, Zhang X, Bai L, Yang H, Lu Z, Li H.
PKM1 Exerts Critical Roles in Cardiac Remodeling Under Pressure Overload in the Heart
Li Q, Li C, Elnwasany A, Sharma G, An YA, Zhang G, Elhelaly WM, Lin J, Gong Y, Chen G, Wang M, Zhao S, Dai C, Smart CD, Liu J, Luo X, Deng Y, Tan L, Lv SJ, Davidson SM, Locasale JW, Lorenzi PL, Malloy CR, Gillette TG, Vander Heiden MG, Scherer PE, Szweda LI, Fu G, Wang ZV.