The Bristow Laboratory investigates chronic heart failure, specifically the molecular mechanisms involved in the genesis and progression of pathologic hypertrophy and contractile dysfunction that are hallmarks of this disease. We measure myocardial gene expression in human clinical studies, and we also work with animal and cell models to gain an understanding of how gene expression changes relate to phenotypic changes and/or differences. More recently, based on previous work we did with the human heart ACE2 enzyme, we have added to the area of investigation mechanisms by which the SARS-CoV-2 virus attaches to, enters and damages myocardial cells.
Our studies correlating expression and phenotype have also allowed us to determine some of the genetic basis for the variability in therapeutic responses routinely observed for most classes of drugs, and these observations have been useful in the development of new pharmaceutical and device-based approaches to treat heart failure and other cardiovascular diseases. Over a more than 30 year period we have collected and processed diseased and control human heart samples from transplant and organ donor programs to create what is likely the largest tissue bank of its kind in the world. This tissue bank has proved extremely helpful in generating key hypotheses about important pathophysiological mechanisms, as well as in the discovery of genetic variants important in therapeutic responses.
A genotype-directed comparative effectiveness trial of Bucindolol and metoprolol succinate for prevention of symptomatic atrial fibrillation/atrial flutter in patients with heart failure: Rationale and design of the GENETIC-AF trial.
Genetic variants are not associated with outcome in patients with coronary artery disease and left ventricular dysfunction: results of the Genetic Substudy of the Surgical Treatment for Ischemic Heart Failure (STICH) trials.