Section of Endocrinlogy

• Zhiyong Zhao, Associate Research Scientist
  Special Interests:Developmental Biology

Current Grant Support

Name	Title	Funding Agency	Dates
Zhiyong Zhao	Influence of Rho GTPases and ROCK kinases on heart development	American Heart Association	7/1/02-6/30/05

Honors and Awards for 2001 and 2002:

• Zhiyong Zhao, American Heart Association Young Investigator Award

Publications for 2001 and 2002:

Original reports:
Zhao, Z. and Rivkees, S. A. (2001). Inhibition of cell proliferation in the embryonic myocardium by A1 Adenosine receptor activation. Developmental Dynamics 221, 194-200.

Zhao, Z. and Rivkees, S. A. (2003). Rho-associated kinases play an essential role in cardiac morphogenesis and cardiomyocyte proliferation. Developmental Dynamics 226:24-32.

Wei, L., Roberts, W., Wang, S., Yamada, M., Zhang, S., Zhao, Z., Rivkees, S.A., Schwartz, R.J. and Yoshida, K.I. (2001) Rho kinases play an obligatory role in vertebrate embryonic organogenesis. Development 128, 2953-2962.

Reviews and Chapters:
Rivkees, S.A., Zhao, Z., Porter, G. and Turner, C. (2001). Influences of adenosine on the fetus and newborn. Molecular Genetics and Metabolism 74, 160-171.

Research Interests and Activity
Our research is focused on Rho GTPases and Rho-associated kinases (ROCKs) in heart formation. Rho GTPases are intracellular signaling tranducers that mediate the effects of extracellular signaling factors. Rho GTPases exert their effects through activating their downstream effectors including ROCK kinases. To investigate the roles of Rho GTPases and ROCK kinases in cardiac development, we first examined the expression patterns of these genes and localization of these proteins in the developing heart. We then disrupted the activity of ROCK kinases in the embryos using ROCK inhibitor Y-27632 and examined the effects of ROCK inhibition on cardiac development. We have found that inhibition of ROCK activity causes cardiac malformations including cardia bifida and cardiac hypoplasia. We also investigated the mechanisms by which the Rho/ROCK system influences heart development. Using BrdU incorporation assays, we found that ROCKs influence cardiac cell proliferation. We also found that ROCKs affect cell proliferation by influencing the expression of cell cycle proteins, cyclin D3, CDK6, and p27KIP1. Our work demonstrates that the Rho/ROCK signaling system plays an important role heart formation. This work also provides information about the mechanisms of congenital cardiac defects and for development of therapeutic drugs.