Cell biology, calcium handling, electrophysiology, regenerative medicine, stem cells. Disease interests: heart failure, congenital heart disease, cardiomyopathy, channelopathies
The Wagner laboratory research investigates postnatal changes in contractility and calcium handling in the heart, in particular, in human development. We have the unique ability to do extensive experiments from molecular analysis to single cell studies and to tissue contractility measurements, creating an integrated approach. Our focus on developmental differences in regulation of calcium handling by the heart, may suggest alternate treatment strategies which are developed specifically for the pediatric cardiac patient. We are particularly interested in the interaction of pathology and development in terms of alterations in whole heart function and single cell mechanics and calcium handling. We currently have several projects underway. A main focus of our laboratory is to examine electro-mechanical activity in single ventricular cells at different developmental ages. We have unique access to ventricular samples from children with congenital heart disease where removal of tissue is required as part of the surgical repair of their heart. We are able to isolate single cells from these samples and use live cell imaging to examine intracellular calcium movement as well as cell shortening. In addition we use patch clamp techniques to measure ionic currents in these cells. We have found significant changes in cell morphology, calcium movement and calcium current pharmacology which have identified potential molecular targets for therapy. Since these human samples are from children with congenital heart defects, we have developed several animal models to recapitulate some of the pathologies seen in these patients. We have a neonatal right heart failure model in rabbit caused by banding of the pulmonary artery. We also have a right ventricular failure model in juvenile rats. Through these animal models, we have recapitulated some of the dysfunction we measure in the human studies. Ultimately, we hope to identify novel targets for therapy for the pediatric heart through our basic science studies. To this end, we have identified a small calcium binding protein that has very low levels in the neonatal heart and, in collaboration with the Mike Davis Lab, are using bioactive nanoparticles to deliver this protein to heart failure cells. We have found that the nanoparticles themselves can normalize calcium handling such as decrease calcium leak and decrease calcium sparks. We are also working with the Davis lab to develop a cell based therapy for right heart failure. We obtain cardiac progenitor cells from the pediatric cardiac patients and are developing hydrogels to deliver these cells to the failing heart. We are also actively involved in collaboration with several stem cell researchers at Emory and Georgia Tech (Chunhui Xu, Todd McDevitt and Young-sup Yoon) to use our cell based techniques to characterize the phenotype of cardiomyocytes derived from induced pluripotent stem cells. These collaborative studies are focused on disease modeling and development of cell based therapies.