IBT Discovery Delves into Causes of Heart Damage October 29, 2008

Robert Schwartz, Ph.D., has worked on the muscle gene switching paradigm since 1981 and published his first paper on the subject that year in the journal Biochemistry. Schwartz was the first to show how muscle genes are switched on and off, and his paper opened up this area of research in developmental biology. Now his new research has proved that SRF is the key factor that allows for muscles being able to contract. This is true all along the evolutionary scale—for human, mouse, worm. His work has focused on muscles in the heart. This finding is important in understanding potential causes of heart damage. The study will be available online in Proceedings of the National Academy of Sciences and in an upcoming issue of the journal. Dr. Schwartz is the director of the Texas A&M Health Science Center Institute of Biosciences and Technology at Houston and head of its Center for Molecular Development and Disease. By itself, the factor SRF may regulate up to 1200 genes and requires other cardiac transcription factors working together to restrict cardiac gene activity. SRF and cofactors then turn on the entire cardiac developmental program that allows cardiac muscles to beat and contract. Schwartz was the first researcher to discover the sarcomeric gene switch program that turns on contractile gene activity. SRF is at the top of the muscle regulatory hierarchy. It keeps other genes from taking heart muscles down pathways that are detrimental to healthy development. In short, SRF regulates many different pathways. For example, he has now shown that approximately one-third of the 550 known microRNAs that are gene silencers are most likely regulated by SRF. “This is exciting because we now see that SRF is also involved in heart failure,” said Schwartz. “If SRF is working properly, then it keeps microRNAS in check so you get the right combination of factors to keep your heart working properly. Put another way, defective SRF promotes heart failure. This is a hot developmental discovery in heart research since it advances understanding of what causes heart damage. “ James F. Martin, M.D., Ph.D., professor in the Center for Cancer and Stem Cell Biology at HSC-Institute of Biosciences and Technology, contributed to the PNAS study. Also contributing were Zhiyv Niu and Dinakar Iyer of the Baylor College of Medicine in Houston; Simon J. Conway of the Indiana University School of Medicine in Indianapolis; Kathryn Ivey and Deepak Srivastava of the Gladstone Institute of Cardiovascular Disease in San Francisco; and Alfred Nordheim of Tuebingen University in Germany. Research was supported by the National Institutes of Health and Fondation Leducq Transatlantic Network of Excellence for Cardiovascular Research.

(c) 2005, Institute of Biosciences and Technology                                       Health Science Center, Texas A&M University System