Our research can broadly be defined by three overlapping themes: 

1. High resolution molecular profiling 

Advances in molecular biology and sequencing technologies have been a gamechanger for the granularity of our molecular analyses. While whole genome sequencing and bulk RNAseq have become entirely routine, we venture into the next generation of technologies analyzing genetic variation, transcript usage, genome regulation, and protein abundance in a cell-by-cell manner. Our long term focus in cardiology have led to our specialized approaches in these challenging tissues. In the near term, we continue to examine relationships between single cell variation in molecular readouts and phenotype and genetics in model systems and humans. At the same time we continue advancing our laboratory and analysis approaches as the field matures, more recently integrating protein profiling and long-read RNA sequencing.

2. From Variants to Mechanisms for Cardiology and beyond

In the past several decades, the rate of discovery for genetic signatures of traits and diseases has accelerated at breakneck speeds. While this has enabled population scale analyses of genetic associations, it has also left us with a mechanistic gap in how these signatures relate to their trait. Just recently have we begun to see successful translation of limited targets into clinical therapeutics or actionable risk stratification, but the potential remains vast. Our goal is to unlock these genetic signatures under the belief that each represents a unique biological mechanism which may ultimately be translationally actionable. To accomplish this, we incorporate multi-disciplinary approaches spanning functional genomics, advanced genetic editing, and studies of cellular and model organism physiology. 

3. Identifying the mechanisms of evolved solutions to human cardiovascular disease from across the animal kingdom

We have studied human physiological and genetic diversity extensively, unraveling key biological pathways with hopes of developing the next life-saving therapeutic. While much of this effort is picking through miniscule effect sizes and multifactorial, highly confounded datasets, one group of subjects has always been of particular interest: those with physiological extremes of both health and disease. While the studies of these human populations continue, we ask: Why limit ourselves to the diversity of humankind, when the animal kingdom may offer solutions to cardiovascular problems that plague our species?

To further this bio-inspired approach, we use the advanced molecular approaches described above, and together with the expertise of our collaborators ranging from comparative physiologists, veterinarians, comparative genomicists, and biomedical engineers, we work to unlock the secrets of these amazing evolved solutions to the cardiovascular maladies of humankind.