The Foster Lab currently has 2 primary research projects
Project 1: Mitochondrial Channels
We are currently concentrating our research on the molecular basis of cardioprotection by mitochondrial ion channels. Proper balance of ions such as calcium and sodium is essential for mitochondria to maintain an adequate energy supply, in the form of ATP, to support contraction of the heart. Potassium fluxes, through mitochondrial channels, stave off necrotic cell death caused by ischemia-reperfusion injury. Despite their importance to heart function, the proteins responsible mitochondrial ion influx and efflux are unknown. Our lab, in collaboration with Dr. Brian O’Rourke, uses the techniques of protein biochemistry and proteomics to identify mitochondrial ion-handling proteins. Elucidating these targets may spur development of new cardioprotective drugs.
Project 2: Structural and Biochemical Events that Underlie Myocardial Stunning
Using electron microscopy and 3D-image reconstruction we have recently shown that clipping of the C-terminus of cardiac troponin I (cTnI), as might occur in myocardial stunning, affects its ability to regulate tropomyosin position on actin in the presence of Ca2+. cTnI, it seems, is more than a simple inhibitor of muscle contraction in diastole. Rather, it is an active participant in proper thin filament activation during systole. Removal of 17 amino acids from the C-terminal of cTnI is sufficient to destabilize the Ca2+-activated conformation of tropomyosin on actin. These results also suggest that restrictive cardiomyopathy mutations within the same domain may also influence tropomyosin conformation. Collaborators include Dr. Anne M Murphy and Dr. Jennifer Van Eyk of Johns Hopkins and Dr. William Lehman of Boston University School of Medicine.