Research Themes:
Instrumentation, Imaging and Image-Guided Therapy
Systems, Synthetic and Quantitative Biology

Education

PhD (molecular biology), University of Pennsylvania, 1966
MD, University of Pennsylvania, 1963

Research Interests

• NMR spectroscopy of tissues
• Muscle biophysics

Contact Information

University of Washington School of Medicine Translational Center for Metabolic Imaging
Brotman 142  Box 358050
815 Mercer Street
Seattle, WA 98109-4714
Phone: 206-543-3762, 206-543-3037
Fax: 206-543-3495
E-mail

Research Description

Our lab group asks questions about the energetics of cells and organs. The work falls naturally into two interrelated themes: the quantitative description and mechanisms of high-energy phosphate (~P) utilization and the mechanisms of ~P re-synthesis and their metabolic and physiological regulations. A comparative and integrative approach exploits the natural differences in cell types by utilizing a number of physiological, biochemical and biophysical techniques on the molecular, cellular, and organ levels. We choose between human muscle, animal muscle, in vitro muscle or skinned fibers segment preparations, according to the nature of the experimental question posed. We are currently working on several project areas:

• Metabolic integration and control of cellular respiration: 31P, NMR spectroscopy is combined with conventional optical, polargraphic, and biochemical techniques to study the regulation of cellular respiration, control of oxidative phosphorylation and regulation of glycogen metabolism and glycolysis.
  
• Adaptations and plasticity: we manipulate the creatine kinase system by using competitive inhibitors in vivo. The kinetics of the creatine kinase reaction are measured in vivo and in vitro by spin transfer NMR techniques. In creatine-depleted muscle, the effects of competitive inhibitors are a major adaptive change in the entire chemomechanical system: muscle isoforms, mitochondrial enzyme levels and perhaps capillary distribution. These adaptations are similar to what is found in endurance training and lead to the hypothesis that the state of cellular energetics exerts an influence on cell phenotype.
  

Selected Publications

• Chase, P.B., and M.J. Kushmerick. Effect of physiological ADP concentration on contraction of single skinned fibers from rabbit fast and slow muscles. Am. J. Physiol. (in press, 1995).
• McFarland, E.W., M.J. Kushmerick, and T.S. Moer land. The activity of creatine kinase in a contracting mammalian muscle of uniform fiber type. Biophys. J. 67:1912-1924, 1994.
• Blei, M. L., K. E. Conley, and M. J. Kushmerick. Separate measures of ATP utilization and recovery in human skeletal muscle. J. Physiol. (London) 465: 203-222, 1993.
• Kushmerick, M. J., T. S. Moerland, and R. W. Wiseman. Mammalian skeletal muscle fibers distinguished by contents of PCr, ATP and Pi. Proc. Natl. Acad. Sci, USA 89: 7521-7525, 1992.