Dr. Siddharth K. Prakash
The University of Texas Health Science Center at Houston
McGovern Medical School
Department of Internal Medicine
I am a clinician and scientist with a focus on the genetic basis of bicuspid aortic valves (BAV) and a commitment to translate my basic research into clinical detection and prevention of aortic disease. We first showed that rare CNVs and chromosomal aberrations in patients with thoracic aortic aneurysms are enriched for interacting genes that regulate vascular smooth muscle adhesion and contractility. These include rare CNVs involving the MYH11 locus in 16p13.1, which confer the highest additive risk for aortic dissections. We went on to show that rare CNVs are also enriched in patients with BAV, which is the most common cause of thoracic aortic disease. We found that young patients with aortic dissections have the highest prevalence of BAV (50%) and the largest percentage of individuals who harbor rare and recurrent CNVs that affect cardiac or vascular developmental genes. We then showed that copy variation of X chromosome genes is the most significant cause of BAV in women with Turner syndrome (TS), the disorder with the highest prevalence of BAV. I led a multi-institutional genetic study of BAV and other left-sided congenital cardiac defects in TS and identified new candidate genes for BAV. We are now utilizing transgenic zebrafish and patient-derived induced pluripotent stem cells (iPS cells) to investigate the contributions of these rare CNVs to aortic valve defects. We recently parlayed these efforts into our first R01 grant to investigate the genetic basis of early onset BAV disease.