MD, National Taiwan University, Ph.D., Washington University in St Louis
Address: 1150 Room, 11F, College of Medicine, NTU.
TEL: (02)23123456 --88327
Next generation sequencing
2] Non-coding RNA biology
3] Ion channel regulation and electrophysiology
4] Cardiac oxidative stress and arrhythmias
The research interests in Yang lab spans from basic science targeting fundamental mechanisms underlying cardiovascular diseases, to translational medicine aiming at advancing the diagnosis and treatment of cardiomyopathy and arrhythmias. Our current research focuses on:
Deciphering the functional roles of non-coding RNAs in cardiovascular diseases
One of the research focuses in Yang lab is to explore the functional roles of non-coding RNAs, specifically long non-coding RNAs (lncRNA) and snoRNAs, in myocardial diseases and cardiac arrhythmias. Using next-generation sequencing technology, we have completed a comprehensive cardiac transcriptome profiling in human non-failing and cardiomyopathic samples, and have identified distinctive expression pattern and putative functions of hundreds of human cardiac lncRNAs and snoRNAs that are involved in the pathogenesis of cardiomyopathy. By combining comparative genomics and molecular genetics in cellular and animal models, we are beginning to uncover the molecular functions of several interesting lncRNAs and snoRNAs that are involved in myocardial fibrosis, cardiac hypertrophy and electrical remodeling. We are also applying CRISPR (clustered regularly interspaced short palindromic repeats) genome editing technology to control lncRNA expression levels in vitro and in vivo to advance our understanding of the functional roles of various cardiac lncRNAs and snoRNAs. In addition, we are exploring the possibility of using myocardial and circulating lncRNAs as the biomarkers for cardiovascular disease diagnosis and outcome prediction.
Mitochondrial oxidative stress, gap junction remodeling and cardiac arrhythmias
Oxidative stress has been shown to play a critical role in the pathogenesis of cardiac hypertrophy, heart failure and arrhythmias. It has been discovered that increased mitochondrial reactive oxidative species (mitoROS) is responsible for cardiac gap junction protein connexin 43 (Cx43) downregulation, slow conduction and increased arrhythmogenecity in response to enhanced renin-angtiotensin system (RAS) activity. Our recent work has shown that increased cardiac RAS signaling leads to eNOS-mediated caveolin 1 (Cav1) S-nitrosation, decreased Cav1-cSrc interaction, cSrc activation and increased Cx43 degradation. Pharmacological inhibition of mitoROS or cSrc tyrosine kinase abrogates RAS-induced Cx43 downregulation, conduction abnormality and arrhythmias. We are currently exploring the molecular mechanisms transducing RAS signaling to increased mitoROS production, as well as the intriguing molecular function of eNOS in sensing cellular redox status and modulating the electrical functioning in the cardiomyocytes.
Right Ventricular Myocardial Biomarkers in Human Heart Failure. J
Card Fail 2015; S1071-9164(15)00048-2.
Mechanisms of Sudden Cardiac Death: Oxidants & Metabolism.
Circulation Research 2015; 116:1937-55.
3] Mechanisms Contributing to Myocardial Potassium Channel Diversity, Regulation and Remodeling. Trends in Cardiovascular Research. 2015 (Accepted)
Caveolin-1 Modulates Cardiac Gap Junction Homeostasis and
Arrhythmogenecity by Regulating cSrc Tyrosine Kinase. Circulation:
Arrhythmia and Electrophysiology.
Cardiac Sodium Channel Mutations: Why So Many Phenotypes.
Nature Reviews Cardiology
2014. doi: 10.1038/nrcardio.2014.85. [Epub ahead of print]
Mitochondria and Arrhythmias.
Free Radical Biology & Medicine.
Deep RNA Sequencing Reveals Dynamic Regulation of Myocardial Noncoding
RNA in Failing Human Heart and Remodeling with Mechanical Circulatory
8] Oxidative stress and atrial fibrillation: finding a missing piece to the puzzle. Circulation 2013;128(16):1724-6. [Abstract]
9] Unfolded protein response regulates cardiac sodium current in systolic human heart failure. Circ Arrhythm Electrophysiol 2013;6(5):1018-24.
10]Exercise training and PI3Kα-induced electrical remodeling is independent of cellular hypertrophy and Akt signaling. J Mol Cell Cardiol 2012; 53(4):532-41.