Samantha Harris
Associate Professor
samharris@ucdavis.edu
Neurobiology, Physiology and Behavior
Office
189 Briggs Hall
(530) 752-0642
Lab
(530) 754-9860
Degrees:
1995
PhD
University of Michigan
(Physiology)
1988
BS
University of Illinois
(Biology)
Research Interests:
Research in my lab is focused on understanding the molecular mechanisms of cardiac contraction and the role contractile proteins play in inherited cardiomyopathies and heart failure. Muscle contraction, including contraction of the heart, occurs as the result of cyclic interactions between myosin and actin, two of the major contractile proteins found in muscle. Numerous other contractile proteins also contribute to contraction and help determine the force and speed of contraction, factors which in turn affect the strength and speed at which the heart pumps blood. Recent discoveries show that many instances of heart disease, including many instances of sudden death in otherwise young, healthy individuals, are due to defects in contractile proteins. Multiple, distinct defects in over 10 different contractile proteins have been identified that together account for a wide spectrum of disease symptoms from very mild to sudden death. Understanding how these numerous contractile proteins work together to produce force and how defects in them can ultimately lead to disease is the central research interest of my lab.
To pursue these research questions we employ a combination of genetic, molecular, biochemical, and biophysical approaches. In particular, we’ve used gene targeting techniques to “knockout” or alter specific myofilament proteins. Structural and functional deficits produced by these genetic manipulations are then assessed using a variety of echocardiographic, histological and ultrastructural imaging, and northern and western blotting methods. Mechanical force measurements, including measurements of shortening velocity, rate of activation, and isometric tension are utilized to determine the functional effects of mutations on force in individual heart cells. Results from these studies provide a better understanding of the molecular mechanisms of muscle contraction and how defects in contractile proteins can cause altered heart function and ultimately lead to disease.
Awards:
American Heart Association, Western States Affiliate, Laverna Titus Young Investigator Award, 2008
American Heart Association New Investigator Award, 2003
American Heart Association McClain Research Award, 2002
American Heart Association Chippewa Valley Research Award, 1998
American Physiological Society Caroline tum Suden Professional Opportunity Award for Meritorious Research, 1993
Department and Center Affiliations:
Department of Physiology and Membrane Biology, UC Davis School of Medicine
Neurobiology, Physiology, and Behavior
Professional Societies:
American Heart Association
American Physiological Society
Biophysical Society
CBS Graduate Group Affiliations:
Biophysics
Molecular, Cellular, and Integrative Physiology
Exercise Science
Publications:
Last updated 5/21/2010
J.F.Shaffer, R.W. Kensler, and S.P. Harris. The Myosin Binding Protein C Motif Binds to F-Actin in a Phosphorylation Sensitive Manner. Journal of Biological Chemistry 284:12318-12327, 2009.
A.E. Whitten, C.M. Jeffries, S.P. Harris*, and J.Trewhella*. Cardiac Myosin Binding Protein-C Decorates F-Actin: Implications for Cardiac Function. *Corresponding authors. PNAS 105:18360-18365, 2008.
P.K. Luther, P. M. Bennett, C. Knupp, R. Craig, R. Padrón, S.P. Harris, J. Patel, and R.L. Moss. Understanding the Organisation and Role of Myosin Binding Protein C in Striated Muscle by Analysis of Normal and MyBPC Knockout Muscle. J Mol Biol 348:60-72, 2008.
M.V. Razumova, K.L. Bezold, A.Y. Tu, M. Regnier, and S.P. Harris. Contribution of the Myosin Binding Protein-C Motif to Functional Effects in Permeabilized Rat Trabeculae. J Gen Physiol 132: 575-85, 2008.
C.M. Jeffries, A.E. Whitten, S.P. Harris, and J. Trewhella. Small-Angle X-ray Scattering Reveals the N-Terminal Domain Organization of Cardiac Myosin Binding Protein C. J Mol Biol. 377:1186-1199, 2008.
R.W. Kensler and S.P. Harris. The Structure of Isolated Myosin Thick Filaments from cMyBP-C Knockout Mice. Biophys J, 2008 Mar 1;94(5):1707-18. Epub 2007 Nov 9.
J.F. Shaffer, M. Razumova, A-Y Tu, M. Regnier, and S.P. Harris. Myosin S2 is Not Required for Effects of Myosin Binding Protein-C on Motility. FEBS Letters, 581: 1501-1504, 2007.
M. Razumova, J. Shaffer, A.Y. Tu, G. Flint, M. Regnier, and S.P.Harris. Effects of the N-Terminal Domains of Myosin Binding Protein-C in an In Vitro Motility Assay: Evidence for Long-Lived Cross-Bridges. Journal of Biological Chemistry, 281:35846-35854, 2006.
S.P. Harris, E. Rostkova, M. Gautel, and R.L. Moss. Binding of Myosin Binding Protein-C to Myosin Subfragment S2 Affects Contractility Independent of a Tether Mechanism. Circulation Research, 95:930-936, 2004.
B.M. Palmer, D. Georgakopoulos, P.M. Janssen, Y. Wuang, D.F. Belardi, P.G. Burgon, C.E. Seidman, J.G. Seidman, S.P. Harris, R.L. Moss, N.R. Alpert, D.W. Maughan, and D.A. Kass. Role of Cardiac Myosin Binding Protein C in Sustaining Left Ventricular Systolic Stiffening. Circulation Research, 94:1249-55, 2004.
F.S. Korte, K.S. McDonald, S.P. Harris, and R.L. Moss. Loaded Shortening, Power Output, and Rate of Force Redevelopment are Increased with Knockout of Cardiac Myosin Binding Protein-C. Circulation Research, 93:752-758, 2003.
S.P. Harris, W.T. Heller, M.L. Greaser, R.L. Moss, and J. Trewhella. Solution Structure of Heavy Meromyosin by Small-Angle Scattering. Journal of Biological Chemistry, 278:6034-6040, 2003.
S.P. Harris, C.R. Bartley, T.A. Hacker, K.S. McDonald, P.S. Douglas, M.L. Greaser, P.A. Powers, and R.L. Moss. Hypertrophic Cardiomyopathy in Cardiac Myosin Binding Protein-C (cMyBP-C) Knockout Mice. Circulation Research, 90:594-601, 2002.
S.P. Harris, J.R. Patel, L.J. Marton, and R.L. Moss. Polyamines Decrease Ca2+ Sensitivity of Tension and Increase Rates of Tension Development in Skinned Cardiac Myocytes. American Journal of Physiology 279: H1383-1391, 2000.