Current Research and Scholarly Interests
Our primary interests are in understanding the molecular underpinnings of vascular disease as well as assessing disease risk. We use a wide range of biochemical, molecular and physiological techniques to make primary observations in cell systems as well as preclinical models. Furthermore, we continue to extend our findings to human subjects in order to confirm their clinical applicability. Current research projects include:
Mechanisms regulating atherosclerosis and abdominal aortic aneurysm disease: While single genes can have dramatic effects in cellular biology, it is becoming increasingly clear that vascular disease (and health) is regulated by the coordinated expression of gene cassettes or pathways. By monitoring expression patterns of the entire genome simultaneously, we can begin to identify networks of genes that work in concert to affect disease progression. Moreover, this approach can often implicate specific nexus genes that are at the center of larger networks and/or participate in multiple pathways. Additionally, we are investigating the role microRNAs, a newly discovered class of small RNA molecues, in orchestrating the activity of multiple genes during the course of disease.
Role of insulin resistance: Reduced activity of the endogenous hormone, insulin, is now recognized as a cardinal feature of type 2 diabetes and an independent risk factor for cardiovascular disease. We have investigated the effects of insulin resistance in several tissues and have recently focused our attention on adipose tissue biology and how it relates to CVD. Long known as a storage vehicle for excess calories, the fat cell is now recognized to be a factory of different products that can not only affect local activity, but can circulate in the blood as hormones and regulate many biological processes. For example, we have recently reported that the novel hormone, apelin, is produced by fat tissue and has important effects upon insulin resistance, obesity and diabetes, all of which have significant implications for cardiovascular disease.
Biomarkers for risk assessment: In addition to target identification, we are applying transcriptional profiling and pathway analysis for another important aspect of cardiovascular disease management--biomarker discovery. As the name connotes, a biomarker should be a good indication of the disease state and thereby allow for early detection as well as monitoring disease progression and, hopefully, efficacy of an applied therapy. Biomarkers can encompass a wide range of molecules including DNA variants, RNA, proteins, as well as lipids. They can even encompass modalities such as molecular imaging. We are engaged in not only identifying novel biomarkers for cardiovascular disease, but also in producing algorithms that combine multiple biomarkers to optimally assess risk.