Samantha (Sam) Harris, PhD

Associate Professor, Cellular and Molecular Medicine
Research Interests: 

The long-term goal of research in my lab is to understand the molecular mechanisms of muscle contraction. I am especially interested in how contractile proteins of muscle sarcomeres regulate the force and speed of contraction in the heart. The question is important from both basic science and clinical perspectives because mutations in sarcomere proteins of muscle are a leading cause of hypertrophic cardiomyopathy (HCM), the most common cause of sudden cardiac death in the young and a prevalent cause of heart failure in adults. Myosin binding protein-C (MyBP-C) is a muscle regulatory protein that speeds actomyosin cycling kinetics in response to adrenaline (b-adrenergic stimuli) and is one of the two most commonly affected proteins linked to HCM. Currently, the major research focus in my lab is understanding the mechanisms by which cMyBP-C regulates contractile speed and mechanisms by which mutations in cMyBP-C cause disease.

In pursuing these interests I have established a variety of approaches to investigate muscle contraction at molecular, cellular, and whole animal levels. Methods include single molecule atomic force microscopy (AFM), mechanical force measurements in permeabilized muscle cells, in vitro motility assays, biochemical enzyme and binding assays, immunofluorescent imaging, knockout/transgenic animal models and the development of a natural large animal model of HCM.

Molecular Medicine Grad Program: 
Yes

Bibliography

2016

van Dijk, S. J., K. Bezold Kooiker, S. Mazzalupo, Y. Yang, A. S. Kostyukova, D. J. Mustacich, E. R. Hoye, J. A. Stern, M. D. Kittleson, and S. P. Harris, "The A31P missense mutation in cardiac myosin binding protein C alters protein structure but does not cause haploinsufficiency.", Arch Biochem Biophys, 2016 Jan 8. PMID: 26777460
Harris, S. P., B. Belknap, R. E. Van Sciver, H. D. White, and V. E. Galkin, "C0 and C1 N-terminal Ig domains of myosin binding protein C exert different effects on thin filament activation.", Proc Natl Acad Sci U S A, vol. 113, issue 6, pp. 1558-63, 2016 Feb 9. PMCID: PMC4760775  PMID: 26831109

2015

van Dijk, S. J., C. C. Witt, and S. P. Harris, "Normal cardiac contraction in mice lacking the proline-alanine rich region and C1 domain of cardiac myosin binding protein C.", J Mol Cell Cardiol, vol. 88, pp. 124-32, 2015 Nov. PMCID: PMC4663077  PMID: 26455481

2014

van Dijk, S. J., K. L. Bezold, and S. P. Harris, "Earning stripes: myosin binding protein-C interactions with actin.", Pflugers Arch, vol. 466, issue 3, pp. 445-50, 2014 Mar. PMCID: PMC4306388  PMID: 24442149

2013

Bezold, K. L., J. F. Shaffer, J. K. Khosa, E. R. Hoye, and S. P. Harris, "A gain-of-function mutation in the M-domain of cardiac myosin-binding protein-C increases binding to actin.", J Biol Chem, vol. 288, issue 30, pp. 21496-505, 2013 Jul 26. PMCID: PMC3724610  PMID: 23782699