BBS Faculty Member - Da-Zhi Wang

Da-Zhi Wang

Department of Pediatrics

Boston Children's Hospital
Enders 1260
320 Longwood Avenue
Boston, MA 02115
Tel: 617-919-4768
Fax: 617-731-0787
Email: dwang@enders.tch.harvard.edu
Visit my lab page here.



Cardiovascular development and disease, muscle biology, non-coding RNAs

Our lab is interest in the molecular mechanisms that regulate animal development, cell fate determination, as well as related human diseases. We apply cardiac and skeletal muscle as our model systems and we unitize both in vitro and in vivo studies. In particular, we study transcriptional regulation and miRNA-mediated post-transcriptional regulation and have made significant contributions to our understanding of the molecular mechanisms controlling cardiac, skeletal and smooth muscle gene expression during development and function. We study the myocardin family of transcription factors and their roles in the cardiovascular system. In the past ten years, we have focused on the role of non-coding RNAs, including microRNAs (miRNAs) and long non-coding RNAs (lncRNAs), in the regulation of gene expression in normal and diseased cardiovascular systems.

Non-coding RNAs represent more than 98% of our genomic sequences, and they are now known to be actively transcribed. We have identified and investigated many miRNAs and lncRNAs that control mammalian heart growth and differentiation, cardiac muscle differentiation and regeneration, and play a role in human cardiovascular disorders, such as congenital heart defects, cardiac hypertrophy and heart failure. We apply a variety of molecular, cellular, and genetic approaches, and we have generated transgenic and knockout mice to study the in vivo function of these important non-coding RNAs. Our studies have significantly contributed to our understanding of the molecular mechanisms underlying cardiac development and function. Most recently, we studied the function of lncRNAs, and we reported that lncRNAs participate in the regulation of smooth muscle proliferation and atherosclerosis. We also develop cutting-edge technologies and apply AAV-based experimental approaches to define the in vivo function of novel lncRNAs that we identified in diseased hearts. Our ultimate goal is to develop novel therapeutic targets to treat human cardiovascular disease.

Current research in the lab has been focused on five major areas:

1. Transcriptional and epigenetic regulation of gene expression in the cardiovascular system
2. microRNAs in cardiac development, cardiac function and cardiomyopathy
3. The roles of miRNAs and epigenetic regulators in skeletal muscle biology
4. Novel lncRNAs in cardiovascular biology and disease
5. Molecular mechanisms of cardiac remodeling and stress-induced cardiac defects



Last Update: 7/27/2016



Publications

Wang, DZ, Chang, P.S., Wang, Z, Sutherland, L., Small, E., Krieg, P.A. and Olson, E.N., 2001. Activation of cardiac gene expression by Myocardin, a transcriptional cofactor for serum response factor. Cell 105, 851-862.

Chen JF, Mandel EM, Thomson JM, Wu Q, Callis TE, Hammond SM, Conlon FL,
Wang DZ. 2006. The role of microRNA-1 and microRNA-133 in skeletal muscle proliferation and differentiation. Nat Genet. 38: 228-233.

Ding J, Chen J, Wang Y, Kataoka M, Ma L, Zhou P, Hu X, Lin Z, Nie M, Deng ZL, Pu WT,
Wang DZ. 2015. Trbp regulates heart function through miRNA-mediated Sox6 repression. Nat Genet. 47:776-83.

Huang ZP, Kataoka M, Chen J, Wu G, Ding J, Nie M, Lin Z, Liu J, Hu X, Ma L, Zhou B, Wakimoto H, Zeng C, Kyselovic J, Deng ZL, Seidman CE, Seidman JG, Pu WT,
Wang DZ. 2015. Cardiomyocyte-enriched protein CIP protects against pathophysiological stresses and regulates cardiac homeostasis. J Clin Invest. 125:4122-34.



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of Harvard College