The Wang Laboratory's research mainly focuses on genetic and molecular mechanisms of heart failure and metabolic disorders. We have made major advances in uncovering stress-signaling mechanisms in the pathogenesis of heart failure, and revealed the functional importance of amino acid catabolism in heart failure and metabolic disorders. In addition, we have reported novel regulatory mechanisms in cardiac transcriptome reprogramming, involving RNA-splicing regulation and non-coding RNA-mediated epigenetic modulation.
Our research seeks to understand the intracellular signaling networks involved in the stress response within mammalian cells, and translating that knowledge into potential therapies. We have three related areas of investigation:
- Discovering novel components in stress-signal transduction networks
- Establishing functional and molecular links among signaling pathways
- Translating mechanistic insights into novel therapies in disease models of heart failure.
Our work has led to the publication of more than 180 peer-reviewed scientific reports in high-quality scientific journals, including Nature Medicine, Journal of Clinical Investigation, Circulation, Circulation Research, and the Proceedings of the National Academy of Sciences (PNAS). Three of our recent publications with significant novelty and potential impact on the field of heart failure research and basic signal transduction are listed below. These studies illustrate the principal feature of our research: developing state-of-the-art experimental tools to explore frontier areas in biology and medicine.
Yibin Wang, PhD, is currently Professor of Molecular Medicine in the David Geffen School of Medicine at UCLA and Chair of the Cardiovascular Theme at UCLA. Dr. Wang received his Ph.D. in molecular genetics and cell biology from Baylor College of Medicine, and post-doctoral training in neurobiology and molecular cardiology at The Scripps Research Institute and the University of California at San Diego.
Gao C, Ren S, Lee JH, Qiu J, Chapski DJ, Rau CD, Zhou Y, Abdellatif M, Nakano A, Vondriska TM, Xiao X, Fu XD, Chen JN, Wang Y. RBFox1-mediated RNA splicing regulates cardiac hypertrophy and heart failure. J Clin Invest. 2016;126(1):195-206. PMCID: PMC4701548. https://www.ncbi.nlm.nih.gov/pubmed/?term=PMC4701548
This is the first paper revealing that RNA-splicing reprogramming is an important part of the pathogenesis of heart failure. RBFox1 is not only a master regulator of heart failure-associated, RNA-splicing reprogramming, but also a gene with major impact on the progression of heart failure under pathological stressors.
Zhihua Wang, Xiao-Jing Zhang, Yan-Xiao Ji, Peng Zhang, Ke-Qiong Deng, Jun Gong, Shuxun Ren, Xinghua Wang, Iris Chen, He Wang, Chen Gao, Tomohiro Yokota, Yen Sin Ang, Shen Li, Ashley Cass, Thomas Vondriska, Guangping Li, Arjun Deb, Deepak Srivastava, Huang-Tian Yang, Xinshu Xiao, Hongliang Li, Yibin Wang. A Long Non-coding RNA Defines an Epigenetic Checkpoint for Cardiac Hypertrophy. 2016, Nature Medicine Epub 2016/09/13. doi: 10.1038/nm.4179. PMID: 27618650. https://www.ncbi.nlm.nih.gov/pubmed/?term=27618650
This is a major report on the discovery of the functional importance of a non-coding gene, named the cardiac-hypertrophy-associated epigenetic regulator (Chaer), in the pathogenesis of cardiac hypertrophy and pathological remodeling. This paper received editorial comments from numerous on-line scientific blogging sites and Circulation Research.
Haipeng Sun, Kristine Olson, Chen Gao, Domenick A. Prosdocimo, Meiyi Zhou, Zhihua Wang, Darwin Jeyaraj, Ji-Youn Youn, Shuxun Ren, Olga Ilkayeva, Svati Shah, Christopher B. Newgard, Hua Cai, Peipei Ping, Isaac George, Paul Christian Schulze, Kemal Akat, Thomas Tuschl, Christopher Lynch, Mukesh K. Jain, Yibin Wang. Branched-Chain Amino Acid Catabolic Reprogramming in Heart Failure. Circulation 2016;133(21):2038-49. Epub 2016/04/10. doi: 10.1161/circulationaha.115.020226. PMID: 27059949.). https://www.ncbi.nlm.nih.gov/pubmed/?term=PMID%3A+27059949
This is a groundbreaking discovery on the role of an amino acid catabolic defect in heart failure and contractile dysfunction. By targeted manipulation of branched amino acid flux, the study shows the potential of restoring BCAA catabolic flux as a potential therapy for heart failure. This study received editorial comment from Science Translational Medicine.