Earl E. Homsher, Ph.D.

Work Address:
CHS
Los Angeles, CA 90095 CHS
Los Angeles, CA 90095

Affiliations
Affiliations
Professor Emeritus, Physiology
Research Interests
The mechanism by which muscle or other molecule motors convert chemical energy (ATP) into mechanical work force, and shortening and the calcium regulation of these processes are studied in our lab. To do this we use a variety of biochemical and biophysical techniques including: transient kinetics in solutions of isolated contractile proteins to study the rates of motor protein reaction steps; measurement of force, displacement, and stiffness in isolated single muscle cells and single myofibrils contracting under conditions controlled by perfusion of the contracting cell with a solution of known concentrations of ATP, ADP, Pi, and or pCa and pH; and the recently developed in vitro motility assays (in which the motion of single fluorescently labeled thin filament propelled by one or more motor protein molecules is measured by quantitative video microscopy under varying biochemical conditions), or the force exerted by a single thin filament is a single myosin molecule using an optical trap. The mechanical effects of replacement of endogenous regulatory protein by protein chimeras will allow us to explore the mechanism of protein signalling and contractile regulation. Using these approaches we hope to determine size of the crossbridge power stroke, the rates of specific reaction steps, and the identity of those steps controlling force and displacement as well as the ediology of the hypertrophic cardiomypathy.
Biography

Research Interest: Regulation of crossbridge mechanisms We study the mechanism by which muscle or other molecular motors convert chemical energy (ATP) into mechanical work force, and shortening (chemomechanical transduction) and the calcium regulation of these processes. For this we use a variety of biochemical and biophysical techniques including: measurement of force, displacement, and stiffness in single muscle cells contracting under controlled conditions; measurement of the force exerted on single reconstituted fluorescently labled thin filaments (using microneedles) and their unloaded sliding speed in in vitro motility assays; measurement of force transients using single isolated myofibrils; and meaurements of force and displacement produced by single myosin molecules using optical trapping techniques. Reconstituted thin filaments are constructed from native and/or molecularly engineered actin, tropomyosin and/or troponin. We hope to learn the size of the crossbridge power stroke, the rates of specific crossbridge reaction steps, the identity of those steps affected by force exerted, displacement, [Ca+2], and the mechanisms of effects of regulatory protein mutations associated with Familial Hypertrophic Cardiomyopathy.

Publications

A selected list of publications:

Morris, C., L.S. Tobacman, and E. Homsher   Modulation of contractile activation in skeletal muscle by CBMII, a Ca2+-insensitive troponin C mutant, J. Biol. Chem, 2001; 276: 20245-20251.
Sant'Ana Pereria, J., D. Pavlov, M. Greaser, E. Homsher, and R. Moss   Kinetic differences in cardiac myosins with identical loop1 sequences, J. Biol. Chem, 2001; 276: 4409-4415.
Gordon, A., E. Homsher, and M. Regnier   Regulation of Contraction, Physiol. Rev, 2000; 80: 853-924.
Homsher, E Lee, DM Morris, C Pavlov, D Tobacman, LS   Regulation of force and unloaded sliding speed in single thin filaments: effects of regulatory proteins and calcium The Journal of physiology. , 2000; 524 Pt 1: 233-43.
Tobacman, LS Lin, D Butters, C Landis, C Back, N Pavlov, D Homsher, E   Functional consequences of troponin T mutations found in hypertrophic cardiomyopathy The Journal of biological chemistry. , 1999; 274(40): 28363-70.
Burkart, E., M. P. Sumandea, T. Kobayashi, M. Nili, A. F. Martin, E. Homsher, and R.J. Solaro   Phosphorylation or Glutamic Acid Substitution at Protein Kinase C Sites on Cardiac Troponin I Differentially Depress Myofilament Tension and Shortening Velocity, J. Biol. Chem, 2003; 278: 11265-11272.
Heller, MJ Nili, M Homsher, E Tobacman, LS   Cardiomyopathic tropomyosin mutations that increase thin filament Ca2+ sensitivity and tropomyosin N-domain flexibility The Journal of biological chemistry. , 2003; 278(43): 41742-8.
Homsher, E Nili, M Chen, IY Tobacman, LS   Regulatory proteins alter nucleotide binding to acto-myosin of sliding filaments in motility assays Biophysical journal. , 2003; 85(2): 1046-52.
Morris, C.A., L.S. Tobacman, E. Homsher   Correlation of the level of thin filament activation with unloaded shortening velocity of rabbit skinned muscle fibers, J. Physiol. , 2003; 550: 205-215.
Piroddi, N Tesi, C Pellegrino, MA Tobacman, LS Homsher, E Poggesi, C   Contractile effects of the exchange of cardiac troponin for fast skeletal troponin in rabbit psoas single myofibrils The Journal of physiology. , 2003; 552(Pt 3): 917-31.