Edward (Ned) Debold
B.S.E. Seton Hall University, 1992; M.S. University of Massachusetts, 1997; Ph.D., Marquette University, 2002; Post-Doctoral Fellowship, University of Vermont, 2008
Muscular fatigue and heart failure
During intense contractile activity the ability of muscle to generate force and motion rapidly declines, a process known as muscular fatigue. Despite extensive study the molecular mechanisms underlying this phenomenon remain poorly understood. We are interested in elucidating these molecular mechanisms in order to improve our basic understanding of muscle function and to develop more effective treatments for diseases related to fatigue, including ischemic heart disease and chronic heart failure. The force and motion generating capacity of muscle is ultimately derived from the conformational changes of muscle’s molecular motor, myosin, as it interacts with actin in a process powered by the hydrolysis of ATP. Therefore to determine the root molecular causes of muscular fatigue we study the mechanics and kinetics of myosin function using state-of-the-art-single molecule biophysical techniques.
Recent insights into muscle fatigue at the cross-bridge level. Debold EP.Front Physiol. 2012;3:151. Epub 2012 Jun 1.
Phosphate enhances myosin-powered actin filament velocity under acidic conditions in a motility assay. Debold EP, Turner MA, Stout JC, Walcott S. Am J Physiol Regul Integr Comp Physiol. 2011 Jun;300(6):R1401-8. Epub 2011 Feb 23.
Human actin mutations associated with hypertrophic and dilated cardiomyopathies demonstrate distinct thin filament regulatory properties in vitro. Debold EP, Saber W, Cheema Y, Bookwalter CS, Trybus KM, Warshaw DM, Vanburen P. J Mol Cell Cardiol. 2010 Feb;48(2):286-92.
Effect of low pH on single skeletal muscle myosin mechanics and kinetics. Debold EP, Beck SE, Warshaw DM. Am J Physiol Cell Physiol. 2008 Jul;295(1):C173-9. Epub 2008 May 14.
Cardiac myosin missense mutations cause dilated cardiomyopathy in mouse models and depress molecular motor function. Schmitt JP, Debold EP, Ahmad F, Armstrong A, Frederico A, Conner DA, Mende U, Lohse MJ, Warshaw D, Seidman CE, Seidman JG. Proc Natl Acad Sci U S A. 2006 Sep 26;103(39):14525-30.v