Research in the Margulies laboratory focuses primarily on myocardial remodeling and myocardial responses to physiological and pathological stress with an emphasis on multilevel inquiries that balance the benefits and drawbacks of reductionism and integration.
The laboratory has had a longstanding commitment to characterizing the human myocardium through physiological and molecular analyses of tissues obtained at the time of heart transplantation and organ donation. Careful characterization of human myocardial biology permits insights into both the heterogeneity of myocardial adaptations to disease and identification of dominant mechanisms and responses. Human tissue phenotyping also allows selection and validation of appropriate models that permit more mechanistic studies and preclinical inquiries. Active studies utilizing human studies include integrated genetic, epigenetic and genomic inquiries designed to identify molecular mechanisms modifying disease susceptibility, preclinical pharmacologic assessments of novel therapeutics and multilevel characterization of recovery and repair process within human hearts.
The lab has had a longstanding interest in elucidating the responses of severely failing hearts to the mechanical unloading and neurohumoral changes that occur during circulatory assistance. This phenomenology within human hearts and appropriate animal models yields new insights into mechanisms of myocardial plasticity, load-modulated signaling, and the biology of myocardial recovery. Our long-term goal is to identify reliable biomarkers of recoverability and develop targeted therapeutic strategies to promote the recovery of failing hearts.
Our recent studies of cardiac stem/progenitor cells (S/PCs) have stimulated several new lines of research including several versatile in vitro models well-suited to studies of S/PC biology. Integrated use of multiparameter flow cytometry and cell sorting, cell culture, isolated-perfused hearts, and in vitro studies of cell and tissue mechanics models permit us to characterize mechanisms regulating S/PC homing, differentiation and maturation. These models are complemented by tissue engineering approaches that enable manipulation of the myocardial microenvironment, rigorous in vitro characterization of newly differentiated cardiac myocytes, and in vivo translational studies in humans.
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Last updated: 10/05/2016
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