Public Data Commons

Chronic inflammatory DCM involves complex host interactions with a pathogen (viral, bacterial, or fungal) as well as dysregulated host immune responses in high-risk patients with a genetic predisposition. Dr. Miller recently established protocols to capture chromatin accessibility landscape in coronary artery tissues from explanted and donor hearts and Dr. Phillips has established a study to procure and analyze heart transplant recipient myocardial and vascular tissues to be integrated with advanced multi-modal cardiac imaging (e.g., echocardiography, cardiac CT, cardiac MRI, PET, etc) and genetic datasets. Finally, collaborator Dr. McNamara has collected single-cell proteomics data from circulating blood and derived PBMC samples in patients with various stages of inflammatory heart disease. By integrating these multi-modal datasets and tissues (immune cells, cardiac and perivascular tissues) there is an exciting opportunity to identify novel cross-tissue immune modulators underlying the initiation and/or progression of inflammatory DCM. We propose the following aims: Aim 1. Perform snATAC profiling of chronic inflammatory DCM and age-matched myocardial tissues to define cell-type specific regulatory mechanisms. Aim 2. Perform spatial transcriptomics profiling of chronic inflammatory DCM and age-matched myocardial heart tissues to identify region and stage-specific disease mechanisms. Aim 3. Perform integrative multi-modal bioinformatics and statistical analyses to identify shared and tissue specific inflammatory biomarkers associated with clinical outcomes related to HFrEF. Using this multi-dimensional, data-driven approach we expect to resolve both tissue resident and infiltrating immune markers of distinct pathological hallmarks of chronic inflammatory DCM. We expect to identify markers that may precede the adverse cardiac remodeling processes and improve the benefit/risk ratio for both follow-up preclinical and translational studies.