Garcia Anastacia M

The focus of my lab is to better understand the adaptations governing pathological myocardial remodeling and the progression to heart failure in pediatric patients with severe congenital heart disease, such as single ventricle heart disease (SV).The ultimate goal of my research is to develop the critical knowledgebase and infrastructure necessary to identify efficacious therapies for improving outcomes in this vulnerable group. We plan to accomplish this by: 1) better understanding the molecular and metabolic adaptations of pediatric SV heart failure, 2) identifying novel therapeutic targets, 3) developing appropriate animal and cell-based models of pathological remodeling, 4) developing diagnostic and prognostic biomarkers, and 5) integrating multi-omic and functional data into a biologically and clinically relevant context. Through our publications we have demonstrated that the failing SV heart is typified by unique molecular, genetic, and functional changes when compared to the adult or pediatric biventricular failing heart. By using a combination of human cardiac and blood samples in combination with cell and animal models, we have evaluated both the basic biology of SV and have identified interventions that have the potential to address the decline in myocardial function. Currently, a major focus of the lab is to elucidate the molecular mechanisms involved in the modulation of cardiac energy metabolism in SV. This work will be important for the identification and development of drug therapies that improve cardiac function and enhance transplant-free survival in this population. Additionally, we are actively investigating the use of peripheral blood mononuclear cells (PBMCs) as non-invasive molecular biomarkers: 1) as a surrogate of the myocardial metabolic environment and presence of HF, 2) as a readout of inflammatory and immune remodeling, for risk stratification and prediction of clinical outcomes, and 3) as a platform to evaluate therapeutic efficacy of novel drug targets to treat SV pathology.