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The Margulies Lab examines mechanisms of myocardial remodeling to identify targets for therapeutic interventions. Many of our inquiries are initiated by multilevel examinations of explanted human heart tissues obtained at the time of transplantation or organ donation to identify dominant disease features and mechanisms and derive insights from the heterogeneity of myocardial adaptations. The Margulies lab has a longstanding focus on load-dependent myocardial remodeling encompassing studies of both physiologic and pathologic adaptation.  Related to this theme, multiple projects are examining how microtubules and other cytoskeletal elements regulate cardiomyocyte contractility and other cellular processes.  Active areas of inquiry also include disease-associated shifts in cardiac metabolism, mechanisms of inherited cardiomyopathies, and advanced myocardial phenotyping using digital pathology and machine learning techniques.  Our inquiries exploit multiscale techniques and models including ex vivo studies in primary cardiomyocytes and muscle slices and cardiomyocytes; complementary studies using cardiomyocytes and engineered cardiac microtissues derived from induced pluripotent stem cells; discovery-oriented "omics" platforms; and strategic patient-based clinical studies.