We are interested in understanding the fundamental molecular mechanisms and genetic pathways that control the formation and function of muscle cell types (cardiac, skeletal and vascular smooth muscle). In particular, we are interested in the transcriptional control of mammalian heart growth and differentiation, vascular smooth muscle differentiation as well as cell proliferation and differentiation-related human cardiovascular disorders, such as cardiac hypertrophy and heart failure. We also study how the develop and function of those three muscles are modulated by microRNAs (miRNAs), a recently identified class of non-coding small RNAs which play essential roles in regulating gene expression post-transcriptionally.

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 related transcription factors, signaling molecules and miRNAs during mouse development and function.

Understanding the molecular mechanisms that control early cardiovascular development has the potential for exciting therapeutic applications in cardiovascular diseases, the leading cause of death in United States.

Wang, D.-Z., Reiter, S. R., Lin, J. L-C., Wang, Q., Williams, H. S., Krob, S. L., Schultheiss, T. M., Evans, S., and Lin, J. J-C. 1999. Requirement of a novel gene, Xin, in cardiac morphogenesis. Development 126, 1281-1294.

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.

Wang*, D.-Z., Valdez*, M.R, McAnally, J. Richardson, J. and Olson, E.N. 2001. The mef2c gene is a direct transcriptional target of myogenic bHLH and MEF2 proteins during skeletal muscle development. Development 128, 4623-4633.

Shin, C. H., Liu, Z.-P., Passier, R., Zhang, C.-L., Wang, D.-Z., Harris, T. M., Yamagishi, H., Richardson, J. A., Childs, G., and Olson, E. N., 2002. Modulation of cardiac growth and development by HOP, an unusual homeodomain protein. Cell 110, 725-735.

Wang*, D.-Z., Li*, S., Hockemeyer, D., Sutherland, L.B., Wang, Z., Schratt, G., Richardson, J.A., Nordheim, A., and Olson, E.N., 2002. Potentiation of serum response factor activity by a family of myocardin-related transcription factors. Proc. Natl. Acad. Sci. U. S. A. 99, 14855-60.

Wang, D.-Z., Passier, R., Liu, Z-P., Shin, C.H., Wang, Z., Li, S., Sutherland, L.B., Small, E., Krieg, P.A., and Olson, E.N., 2002. Regulation of cardiac growth and development by SRF and its cofactors. Cold Spring Harb Symp Quant Biol. LXVII, 97-105.

Wang, Z., Wang, D.-Z., Pipes, G.C. T., and Olson, E. N., 2003. Myocardin is a master regulator of smooth muscle gene expression. Proc. Natl. Acad. Sci. U. S. A. 100, 7129-7134.

Shijie Li*, Da-Zhi Wang*¹, Zhigao Wang, James A. Richardson and Eric N. Olson1, 2003. The serum response factor coactivator myocardin is required for vascular smooth muscle development. Proc. Natl. Acad. Sci. U. S. A. 100, 9366-9370.

Wang Z, Wang D.-Z, Hockemeyer D, McAnally J, Nordheim A, Olson EN. 2004. Myocardin and ternary complex factors compete for SRF to control smooth muscle gene expression. Nature. 428, 185-9.

Jiyeon Oh*, Zhigao Wang*, Da-Zhi Wang*, Ching-Ling Lien, Weibing Xing, and Eric N. Olson, 2004. Target gene-specific modulation of myocardin activity by GATA transcription factors. Mol. Cell. Biol. 24, 8519-8528.

Wang, D.-Z. and Olson, EN, 2004. Myocardin and cardiac and smooth muscle gene expression. Curr Opin Genet Dev. 14: 558-566.

Li HH, Kedar V, Zhang C, McDonough H, Arya R, Wang DZ, Patterson C. 2004. Atrogin-1/muscle atrophy F-box inhibits calcineurin-dependent cardiac hypertrophy by participating in an SCF ubiquitin ligase complex. J Clin Invest. 114:1058-71.

Cao, D., Wang, Z., Zhang C., Oh, J., Xing, W., Li, S., Richardson, JA, Wang*, D-Z, and Olson*, EN. 2005. Modulation of smooth muscle gene expression by association of histone acetyltransferases and deacetylases with myocardin. Mol. Cell. Biol. 25, 364-376. (*Co-corresponding authors).

Eric M. Small, Andrew S. Warkman, Da-Zhi Wang, Lillian B. Sutherland, Eric N. Olson, and Paul A. Krieg. 2005. Myocardin is sufficient and necessary for cardiac gene expression in Xenopus. Development 132: 987-997.

Elizabeth M. Mandel, Tom Callis, Da-Zhi Wang*, Frank L. Conlon*. 2005. Transcriptional mechanisms of congenital heart disease. Drug Discovery Today. 2, 33-38. (*Co-corresponding authors).

Jim J.-C. Lin, Elisabeth A. Gustafson-Wagner, Haley W. Sinn, Sunju Choi, Shannon M Jaacks, , Sylvia Evans and Jenny L.-C. Lin. 2005. Structure, Expression and Function of a Novel Intercalated Disc Protein, Xin. J. Med. Sci. 25: 215-222.

Thomas E. Callis, Dongsun Cao, and Da-Zhi Wang*, 2005. Bone morphogenetic protein (BMP) signaling modulates myocardin transactivation of cardiac genes. Cir. Res. 97: 992-1000.

Ping Qiu^{1,2^}, Raquel Ritchie^{1,2^}, Zhiyao Fu¹, Dongsun Cao³, Jerry Cumming¹, Joseph M. Miano⁴, Da-Zhi Wang³, Hui J. Li⁵ and Li Li^1,2*, 2005. Myocardin enhances Smad3-mediated TGF-ß1 signaling in a CArG box-independent manner; Smad binding site (SBE) is a critical cis-element for SM22a transcription in vivo. Cir. Res. 97: 983-991.

Jian-Fu Chen^1,2, Elizabeth M. Mandel^1,3, J. Michael Thomson², Qiulian Wu^1,2, Tom E. Callis^1,2, Scott M. Hammond² , Frank L. Conlon^1,3 and Da-Zhi Wang^1,2,*, 2006. The role of microRNAs in SRF-mediated skeletal muscle differentiation. Nature Genetics. 38: 228-33. Epub 2005 Dec 25.

Weibing Xing¹,*, Tong-Cun Zhang¹,*, Dongsun Cao¹, Zhigao Wang², Christopher L. Antos², Shijie Li², Yibin Wang³, Eric N. Olson²,** and Da-Zhi Wang¹,**. 2006. Myocardin induces cardiomyocyte hypertrophy. Cir. Res. (In press).