The long term goal of our research is to contribute to a greater understanding of the causes and consequences of birth defects and to apply this knowledge to the development of new therapeutic strategies in prevention and treatment.
More specifically we want to understand how environmental influences during gestation may adversely affect health outcome. Clinically, this may be manifest at parturition as an identifiable birth defect, or contrastingly, as a phenotypically normal infant who is predisposed, many decades later, to adult onset diseases. The study of birth defects is a critical health concern with serious social and economic consequences because it has been estimated that between 3-7 % of all infants are born with some form of identifiable anomaly, and moreover, birth defects are the leading cause of infant mortality. Although it has been demonstrated that the in utero environment can influence adult health outcomes, the full extent of its impact is unclear.
The ventricular septation defect (VSD) of the heart is the most common malformation noted clinically and in animal models; however, its aetiology remains unclear. To facilitate the study of this defect we have developed a rat model in which approximately 80% of pups present with VSD at parturition, and it is the primary focus of our laboratory. Using this model we aim to understand the common mechanism of action that allows an array of structurally and pharmacologically diverse chemicals to cause VSD. Interestingly, both clinically and in animal models, most VSD spontaneously repair; however, even in cases where the defect has spontaneously closed or been surgically repaired, patients are more susceptible in later life to non septum-related heart health concerns. Our goal is to understand why this is, and the embryological basis for these differences.