Research

My research focuses on understanding the molecular and epigenetic mechanisms that regulate cardiac development.

Current Research

Investigating epigenetic regulation of Hox genes during cardiac development and its implications for congenital heart defects. We already know that epigenetic regulators e.g., trithorax group (trxG), polycomb group (PcG) genes regulate heart development and patterning by activating or repressing transcription during development. We also know that Hox genes are critical for heart development both in fruit fly and mice. Mutations in these epigenetic regulators and Hox genes are directly or indirectly associated with congenital heart defects (CHDs). However, we do not completely understand how trxG and PcG regulate heart development and patterning via hox regulation. Given the necessity of Hox activity and epigenetic regulation in heart development, the goal of my ongoing and future research is to explore the mechanisms by which trxG and PcG genes regulate Hox expression, and thereby, how these genes contribute to CHDs. Congenital heart defects (CHDs) are among the most common birth defects within the United States with a prevalence of approximately 2.4 million individuals of all age groups. High-throughput DNA sequencing investigations of CHD patients have identified deleterious mutations in chromatin modifying genes that may disrupt the expression of key developmental cardiac genes. Several of the identified genes are the human orthologous genes of the Drosophila (fruit fly) trithorax (trxG) group and polycomb group (PcG) which antagonize one another to regulate Hox gene transcription. Individual Hox gene mutations can also generate a spectrum of developmental and congenital abnormalities. For example, the autosomal recessive HOXA1 syndrome patients present with CHDs of varying penetrance and severity. Therefore, trxG and PcG genes likely play critical functions regulating Hox activity within the cardiac genetic network. My current research focuses on identifying and characterizing the roles of trithorax (trx) and polycomb (Pc) genes in cardiac Hox expression and anterior and posterior patterning of the heart using fruit fly (Drosophila melanogaster) heart tube as the system. By defining the functions of these genes my model of trx and Pc regulation of cardiac patterning via Hox control will be able to help to understand the pathogenesis of CHDs.

Techniques

• Immunohistochemistry
• Cell culture
• Cloning
• Embryonic developmental studies