Accumulation of blood-borne leukocytes and their proliferation within the atherosclerotic plaque is a hallmark of atherosclerosis. During disease progression, inflammatory mediators produced by activated neointimal macrophages and lymphocytes induce the proliferation of vascular smooth muscle cells (VSMCs) and their migration towards the growing lesion. Moreover, accumulation of non-cellular material such as modified lipids and extracellular matrix components contribute to atheroma growth. Excessive cellular hyperplasia is also a feature of restenosis, the major limitation to the long-term success of revascularization via stent placement.

Our research addresses the cellular, molecular and genetic mechanisms that underlie the development of atherosclerosis and restenosis, with particular emphasis on the role of cellcycle regulatory factors, as well as the identification of biomarkers of these diseases. Our experimental strategy involves a multifaceted approach that combines in vitro, cellular, animal and human studies and a variety of technologies including mouse genetic engineering, proteomics, transcriptomics, FRET, confocal microscopy, and yeast 2-hybrid screening.

Specific projects in the lab include: 1) Generation and characterization of genetically-modified mice to investigate the role of candidate genes in atherosclerosis, including Cre/lox strategies to ablate genes specifically in cell types involved in atherosclerosis (VSMCs, endothelial cells and macrophages); 2) Studies of the consequences of single nucleotide polymorphisms in cell-cycle regulatory genes on human susceptibility to in-stent restenosis; and 3) Research into the role of the nuclear envelope in the regulation of signal transduction, gene expression and cell-cycle activity in cardiovascular disease and aging, with particular emphasis on A-type lamins and Hutchinson-Gilford progeria syndrome (HGPS).