Mechanisms in the Pathogenesis of Congenital Heart Disease
Our ongoing research to understand the causes of Congenital Heart Disease (CHD) includes:
Perinatal viral infection on development of heart defects in animal models
Our long-term goal is to understand the burden and mechanism(s) of virally-induced CHD. We and others have data to support a role of “cardiotropic” viruses (i.e., viruses that have specific receptors in the fetal heart) in causing heart defects, by interfering with normal development during the critical window of first trimester. These studies have shown infection with type B coxsackievirus (CVB) in early gestation induces heart defects in mice (https://pubmed.ncbi.nlm.nih.gov/33440998/). To determine mechanisms in mediation of heart defects by CVB our studies include examination of the proliferation of CVB and signal transduction pathways.
The coxsackievirus-adenovirus (CAR) receptor plays a critical role in embryonic heart development, supporting our hypothesis that viral infections can be detrimental to normal cardiac formation (https://pubmed.ncbi.nlm.nih.gov/33369284/). Using Cre-lox technology to achieve tissue-specific deletion of the CAR gene we are examining heart development in mice.
Maternal risk factors in women carrying infants with heart defects
By comparing biospecimens in non-pregnant and pregnant women we are examining the influence of environmental and/or modifiable risk factors on development of heart defects in the offspring. Our research focus on examining a potential role for viral infections in CHD include analyses of the maternal gut virome (https://pubmed.ncbi.nlm.nih.gov/31993452/).