Research in my 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. My laboratory has had a longstanding commitment to…
more 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. My research program also includes patient-based in vivo inquiries allowing further validation and translation of lab-based findings. I have had a particular interest in elucidating the responses of severely failing hearts to the mechanical unloading and neurohumoral changes that occur during circulatory assistance. In this area, our long-term goal is to identify reliable biomarkers of recoverability and develop targeted therapeutic strategies to promote the recovery of failing hearts. We have also been using advances in high-throughput genotyping, RNA sequencing and bioinformatics to conduct unique translational and discovery inquiries designed to gain new insights into mechanisms of hypertrophy and failure in human myocardium. Through a multicenter consortium of major heart transplant centers, these inquiries exploit phenotypic variability and involve the first-ever eQTL studies using approximately 2,000 high quality human myocardial specimens.
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