Molecular epidemiology research in the Department of Pathology & Laboratory Medicine encompasses three main areas:
Molecular and Genetic Epidemiology - Cardiovascular disease (CVD)
- HIV, venous thrombosis
- atherosclerosis, stroke
Animal Models - viral myocarditis, atherosclerosis
Clinical Trials - venous thrombosis
Work is centered on molecular risk factors of CVD, with recent interest on inflammation and coagulation and fibrinolysis. Sub-areas include the effects of estrogen replacement therapy on CVD risk and the differing roles of risk factors in predicting CVD in young, middle aged and older people. Inflammation markers also predict incident diabetes, frailty and several other diseases of older people. Interestingly:
- We study a large New England kindred, with many relatives in Vermont, who express a mutation in the protein C gene, and have varying expression of clotting disorders.
- At the Laboratory for Clinical Biochemistry Research (LCBR), we maintain the largest university based repository of CVD-related blood samples and DNA in the country (over 1,000,000 samples representing over 60,000 study participants), and annually perform assays and genotyping on several thousand people.
The animal model work is centered on two areas: myocarditis and atherosclerosis. In both areas we are exploring the immunological basis of disease progression. Recent evidence includes the role of pro-inflammatory cytokines in immune regulation and atherogenesis. Our goal is to use the animal model work and epidemiological studies in a complementary manner to help address new areas for research.
- As an example, from the epidemiological work we observed a relationship of inflammation markers to CVD risk, over long periods of time. This suggested that inflammation might play a role in very early atherosclerosis. We used the mouse model of atherosclerosis to demonstrate that by artificially increasing inflammation mediators we could increase atherosclerosis. With this support we went back to human studies to show that early changes in inflammation markers predicted early development of atherosclerosis as estimated by coronary calcification.
The clinical trial work centers on drugs related to CVD therapy, such as thrombolytic compounds and antiplatelet reagents. The Laboratory for Clinical Biochemistry Research (LCBR) is a core laboratory for many clinical trials, and we often participate in trial design and implementation strategies. We also use clinical trial samples to study biochemical changes associated with drug therapies, such as the loss of coagulation factors during thrombolysis.