- Professor of Medicine, Cardiovascular Division
- Professor of Cell Biology and Physiology
Innate immunity, cardiac remodeling, and myocardial recovery.
Cellular and molecular mechanisms of cardiac remodeling and reverse remodeling
We are interested in the molecular and cellular basis of heart failure, with a particular emphasis on the maladaptive role of inflammatory mediators and innate immunity in disease progression in the failing heart. Our laboratory has focused on innate immune signaling factor in cardiac myocytes and cardiac fibroblasts, as well as in the intact heart using a variety of genetically modified mouse models. Collectively, these studies have suggested that inflammation contributes to cardiac remodeling and the progression of heart failure. A second related area of interest with respect to heart failure biology is the elucidation of the cellular and molecular mechanisms that are responsible for the reversal of the abnormalities of cardiac structure and function (reverse remodeling) following cardiac injury.
Cellular and molecular mechanisms of cytoprotection following cardiac injury
In addition to identifying the maladaptive effects of inflammation in the heat, we have also focused on the adaptive (beneficial) role of inflammatory mediators and innate immunity in the mammalian heart. These studies have identified a potentially important role for tumor necrosis factor receptor adaptor factor 2 (TRAF2) as scaffolding protein that mediates the cytoprotective effects of tumor necrosis factor in the adult heart. More recent studies have begun to use a bioinformatics approach to identify novel cytoprotective signal transduction pathways that are downstream from innate immune signaling in the heart.
Translational (T1, T2, T3) research
Over the past 15 years the Mann laboratory has also sought to translate concepts derived in the laboratory into “transitional” phase II and phase III clinical trials. To this end, Dr. Mann was the Principal Investigator on the RENAISSANCE, RENEWAL, Acorn Pivotal Trial, and the INOVATE-HF trial. These phase III clinical trials have targeted inflammation and/or cardiac remodeling in clinical heart failure.
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