Michael J. Previs, Ph.D.
Dr. Previs received his Ph.D. from the Cell and Molecular Biology Program at the University of Vermont in 2010, with research emphasis on the development of quantitative mass spectrometry-based proteomic techniques to examine muscle structure. Dr. Previs pursued his interest in muscle as a Post-doctoral Associate in the Molecular Physiology & Biophysics Department. In this role he developed single molecule assays to examine the molecular mechanics which underlie muscle function. In 2014, Dr. Previs was promoted to Assistant Professor of Molecular Physiology & Biophysics and is now establishing his own independent research program. Dr. Previs’ lab uses a combination of mass spectrometry-based proteomic strategies and state-of-the-art single molecule imaging techniques to characterize the structure and function of muscle protein complexes in health and disease.
My current research interests are focused on understanding the molecular mechanisms by which myosin binding protein C, a key muscle protein regulates the hearts ability to contract. The heart contracts on a beat-to-beat basis through orchestrated interactions of electrical, chemical and mechanical elements within the sarcomere, the elementary contractile unit. Ultimately, cardiac contraction results from sarcomere shortening due the sliding of actin-based thin filaments past myosin-based thick filaments. Myosin binding protein C is a thick-filament associated regulator of actomyosin sliding, and we have shown that is exerts its functional effects through direct interactions between both the actin- and myosin-based filamentous systems. My current studies are focused on further defining the binding partners involved in these regulatory interactions, and building complexity into my in vitro model systems to understand myosin binding protein C’s function in the presence of additional actomyosin regulatory components which exist within the sarcomere. This work will continue to provide insight why mutations in myosin binding protein C’s gene (MYBPC3) are a leading cause of heart disease including hypertrophic cardiomyopathy.
Swenson AM, Tang W, Blair CA, Fetrow CM, Unrath WC, Previs MJ, Campbell KS, Yengo CM (2017) Omecamtiv Mecarbil Enhances the Duty Ratio of Human β-Cardiac Myosin Resulting in Increased Calcium Sensitivity and Slowed Force Development in Cardiac Muscle. J Biol Chem 292(9): 3768-3778.
Previs MJ, Mun JY, Michalek AJ, Previs SB, Gulick J, Robbins J, Warshaw DM, Craig R (2016) Phosphorylation and calcium antagonistically tune myosin-binding protein C’s structure and function. Proc Natl Acad Sci U S A 113(12): 3239-44.
Woodward M, Previs MJ, Mader TJ, Debold EP (2015) Modifications of myofilament protein phosphorylation and function in response to cardiac arrest induced in a swine model. Front Physiol 6: 199.
Previs MJ, Prosser BL, Mun JY, Previs SB, Gulick J, Lee K, Robbins J, Craig R, Lederer WJ, Warshaw DM (2015) Myosin-binding protein C corrects an intrinsic inhomogeneity in cardiac excitation-contraction coupling. Sci Adv 1(1): .
Mun JY, Previs MJ, Yu HY, Gulick J, Tobacman LS, Beck Previs S, Robbins J, Warshaw DM, Craig R (2014) Myosin-binding protein C displaces tropomyosin to activate cardiac thin filaments and governs their speed by an independent mechanism. Proc Natl Acad Sci U S A 111(6): 2170-5.
Previs MJ, Michalek AJ, Warshaw DM (2014) Molecular modulation of actomyosin function by cardiac myosin-binding protein C. Pflugers Arch 466(3): 439-44.
Miller MS, Bedrin NG, Callahan DM, Previs MJ, Jennings ME 2nd, Ades PA, Maughan DW, Palmer BM, Toth MJ (2013) Age-related slowing of myosin actin cross-bridge kinetics is sex specific and predicts decrements in whole skeletal muscle performance in humans. J Appl Physiol (1985) 115(7): 1004-14.