James A. Hamilton, Ph.D.

Direct Contact: jhamilt@bu.edu

Lab Information

http://www.bumc.bu.edu/busm/2012/10/11/two-boston-university-faculty-members-named-2012-massachusetts-academy-of-sciences-fellows/

Dr. Hamilton’s laboratory is developing and applying novel approaches to study of obesity, metabolic syndrome, and cardiovascular disease. A newer focus is the application of magnetic resonance imaging (MRI) to examine fat tissue and atherosclerosis. These studies extend from animal model systems (mouse and rabbit) to humans. A major focus of our research in obesity and diabetes is on molecular aspects of fatty acid binding interactions and transport in plasma, cell and model membranes, and the cytosol, using state-of-the-art methods in structural and cell biology. These basic science projects include the interactions of fatty acids (FA) with serum albumin by ¹³C-NMR spectroscopy, correlating NMR results with crystallographic data to achieve site-specific information, and determining the complete tertiary structure of intracellular fatty acid binding proteins by NMR. To elucidate mechanisms by which FA cross the membrane barrier between the plasma and the cytosol, we have developed a combination of fluorescence probes to distinguish and quantify individual steps of FA transport in membranes. These novel approaches are now being applied to gain molecular insights into the roles of plasma membrane proteins such as CD36 and caveolins in FA uptake in cells. Understanding the mechanism by which FA move across membranes has immediate and important implications for the treatment of diseases and targeting of pharmacological interventions to reduce accumulation of fat in cells.

The High Field Cardiovascular NMR and MRI Core, under my direction, has recently been upgraded to with advanced imaging electronic and software to enhance all imaging experiments at 11.7T. This improves our ability to image live mice to monitor atherosclerosis and fat accumulation, including serial imaging of the same mouse to follow progression of disease and therapies. In collaborative projects we have imaged fat depots in several mouse models of obesity and leanness. A rabbit model of the acute event of atherosclerosis, plaque rupture and thrombosis is being studied to develop MRI for prediction of unstable and high risk plaques. This project area combines in vivo MRI of live rabbits obtained with the CBI 3T clinical scanner and ex vivo high resolution images at 11.7T. The studies have yielded new MRI protocols that are being applied in pilot studies of humans with advanced carotid atherosclerosis who are undergoing endarterectomy. Newer focuses of the rabbit project of vulnerable plaque include molecular targeting of high risk plaques with probes designed by Nobel Laureate Roger Tsien. Our ongoing study of obese subjects with metabolic syndrome images pericardial fat and liver fat and explores the hypothesis that a unifying feature of metabolic syndrome is enhanced deposition of lipids throughout the body outside of the normal adipose stores. The Hamilton lab emphasizes multidisciplinary collaborative research and is recognized for translation of innovative basic research.