Research interests
The high incidence of congenital heart disease necessitates an understanding of the mechanisms of disease. We are currently focusing on the study of hypoplastic left heart syndrome: a malformation characterized by underdevelopment of the left heart. We are studying the abnormalities in stem cell, growth factor and angiogenic signalling in these hearts and their role in dysregulation of chamber growth. With our collaborators, we hope to identify signalling targets that can be modulated in utero to promote cardiac growth and find cell-based therapies aimed towards this goal.This may help to establish interventions to optimize ventricular growth and function during fetal life in order to reduce the need for complex surgery. In addition, Dr. Mital is the site Principal Investigator for the National Heart, Lung, Blood Institute (NHLBI) sponsored Pediatric Heart Network study of infants with hypoplastic left heart syndrome aimed at assessing clinical and biologic determinants of outcomes.
We also study the molecular basis of right ventricular (RV) failure in cardiac malformations such as tetralogy of Fallot (TOF), the most common cyanotic heart defect and the most common cause of blue baby syndrome. We have previously shown that the right ventricle has an impaired ability to adapt to chronic hypoxia in children with TOF, which may influence long-term RV function. We are now studying the molecular basis for RV myocardial impairment.
A major research interest is the study of genes that cause heart disease using a genome-wide approach. Dr. Mital is the PI of the Heart Centre Biobank which has currently recruited ~1,400 children with heart disease to identify the genetic basis of disease as well as the genetic determinants of outcomes in patients with congenital heart disease and cardiomyopathies. This is an Ontario province-wide effort to enroll children and adults with heart disease for genomic studies (www.sickkids.ca/heartcentrebiobank). International collaborations with centres in France and the Netherlands have also been established for this effort (http://transatlanticgccm.org). We are also studying the influence of single nucleotide polymorphisms on disease phenotype in children with heart disease. This is being done as part of a multi-center, NHLBI funded Pediatric Heart Network ancillary study. Our objective is to identify genetic modifiers of heart disease in children in order to predict risk and tailor pharmacotherapy.