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.



The Wang lab is interested in molecular regulation of mammalian cardiac, skeletal and vascular smooth muscle growth and differentiation, and how these pathways go awry in human cardiovascular and muscular disorders such as congenital heart defect, heart failure and muscular dystrophy. We apply a variety of molecular, cellular, and genetic approaches, including transgenic and knock-out mice, to investigate the in vitro and in vivo functions of transcription factors and microRNAs. In particular, our lab focuses on:

I. Transcriptional and epigenetic control of mammalian cardiovascular development and function. We seek to identify cell growth and differentiation signals that modulate the activity of transcription factors. The lab is also investigating how pathophysiological signals, such as cardiac hypertrophy and congenital heart failure, mediate changes in cardiac gene expression. In addition, we study how epigenetic factors, which modify chromatin, impact cardiac transcription factors and gene expression during cardiovascular development.

II. miRNAs in cardiac muscle development and function. We are investigating the in vivo function of miRNAs in cardiac muscle. The lab is experimentally identifying the mRNA targets of key cardiac miRNAs, using a combination of bioinformatics-based candidate approaches and unbiased screening approaches (genomics and proteomics). These studies will allow us to define the underlying molecular mechanisms for miRNA activity in cardiac muscle cells.

III. miRNAs in skeletal muscle stem cell and regeneration. Skeletal muscle satellite cells are adult stem cells responsible for postnatal skeletal muscle growth and regeneration. We hypothesize that miRNAs are required for proper satellite cell fate determination and self-renewal. We will investigate how miRNAs regulate the self-renewal, proliferation and differentiation of satellite cells. Our studies will shed new lights into the molecular mechanisms of stem cell biology and regenerative medicine.

Congenital heart disease represents one of the most common classes of birth defects in humans. Cardiovascular disease is the leading cause of death in United States. Research conducted in the Wang laboratory, which aims at understanding the molecular mechanisms that control early cardiac development, has the potential for exciting therapeutic applications in cardiovascular diseases.



Last Update: 8/22/2013



Publications

Wang, D.-Z., 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.

Jian-Fu Chen, Elizabeth P. Murchison, Mauricio Rojas, Ruhang Tang, Mariko Tatsuguchi, Thomas E. Callis, Scott M. Hammond, Gerhard Meissner, Craig Selzman, Michael Schneider, Gregory J. Hannon, Cam Patterson and
Da-Zhi Wang. 2008. Targeted Deletion of Dicer in the Heart Leads to Dilated Cardiomyopathy and Heart Failure. Proc. Natl. Acad. Sci. U. S. A. 105: 2111-2116

Thomas E. Callis, Kumar Pandya, Ruhang Tang, Hee Young Seok, Jian-Fu Chen, Monte S. Willis, Craig H. Selzman, Oliver Smithies, and
Da-Zhi Wang. 2009 MicroRNA-208a is a key regulator of cardiac remodeling and conduction. J Clin Invest 119:2772–2786.



© 2013 by the President and Fellows of Harvard College