The overall focus of our research group is on the effects of pro-inflammatory molecules on myocardial growth and gene expression. Several pieces of background information that suggest that these factors may play a significant role in the pathogenesis of several forms of myocardial dysfunction including:
Cytokines are elevated in several cardiac disease states
Cytokines are produced by myocardial cells themselves in response to injury, and
The alterations in gene expression seen in response to cytokines resembles the phenotype of the failing heart.
My laboratory is specifically interested in the role played by Interleukin-1 (IL-1) on the remodeling process following myocardial injury. The overall hypothesis of our work is that the intra-cardiac expression of IL-1 is both a marker of, and progression factor for, the transition to decompensated congestive heart failure. A major focus is on the cardiac fibroblast which represents the predominant cell-type present in the heart, the one with the largest proliferative potential, and the source of the fibrotic response seen in response to injury.
As such, the goal of our work is to define the signaling mechanisms which underlie the following cellular endpoints:
Fibroblast migration and cytoskeletal remodeling
Extracellular matrix metabolism; and
Production of secondary paracrine mediators.
Our approach to these studies include both whole animal and cell culture investigations of both wild-type and transgenic mice that allow for lineage-specific alterations in the cardiac fibroblast in response to aging as well as both pressure-load and myocardial infarction.