Honorary Director, Translational Center for Metabolic Imaging
Professor of Radiology, Bioengineering, Physiology and Biophysics
Research Affiliate, Center on Human Development and Disability
University of Washington
Seattle, WA 98195-7115
Dr. Kushmerick’s laboratory uses MR spectroscopy and imaging and optical spectroscopy in metabolic studies. His research interests include the energetics, economy, and efficiency of muscle contraction, the integration of mechanisms from the molecular to the muscular level, and the design of systems for energy balance.
The overall theme is the signaling, regulation, and interaction of molecular and cellular mechanisms in metabolism to sustain and restore energy balance in muscle. The central idea is energy balance and its restoration when perturbed: ATP usage the demand and metabolic generation of ATP is the supply. The cellular bioenergertic system in muscle is demand driven. In collaboration with Kevin Conley and David Marcinek, he is developing and using these multi-spectroscopic tools to investigate mitochondrial function and dysfunction in human and mouse muscles, focusing on the aging process and selected diseases. A major finding is that the coupling of oxygen uptake to phosphorylation (ATP/O2 ratio) is variable and decreased in aging. The same collaboration also studies the efficiency of muscle’s use of ATP by the contractile machinery. We found the efficiency (ratio energy of work ouput to metabolic energy input) is surprisingly high. It is these basic mechanisms of energy use and energy supply that describe steady state performance capability of muscle. Further the dynamic changes during and following transient perturbations, such as exercise and ischemia, quantify mechanisms of regulation operating to achieve energy balance.
Lab studies cover the range of organization from single isolated animal muscles to intact human limb muscle. Part of the work entails constructing mathematical descriptions of each component and modeling the system to compare with actual physiological performance measures. A systems biology for these muscle mechanisms is the ambitious but eminently feasible goal, grounded in the philosophic view that the limitations in clinical medicine and basic science are the same: lack of mechanistic understanding of the physiological processes.
1. Crowther GJ, Milstein JM, Jubrias SA, Kushmerick MJ, Gronka RK, and Conley KE. Altered energetic properties in skeletal muscle of men with well-controlled insulin-dependent (type 1) diabetes. Am J Physiol Endocrinol Metab 284: E655-662, 2003.
2. Kushmerick M. From Cross Bridges to Metabolism: System Biology for Energetics. Adv Exp Med Biol 565: 171 - 182, 2004.
3. Marcinek DJ, Schenkman KA, Ciesielski WA, Lee D, and Conley KE. Reduced mitochondrial coupling in vivo alters cellular energetics in aged mouse skeletal muscle. J Physiol 569: 467-473, 2005.
4. Marro KI, Hyyti OM, and Kushmerick MJ. FAWSETS perfusion measurements in exercising skeletal muscle. NMR Biomed 18: 322-330, 2005.