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.
Inchingolo AV, Previs SB, Previs MJ, Warshaw DM, Kad NM (2019) Revealing the mechanism of how cardiac myosin-binding protein C N-terminal fragments sensitize thin filaments for myosin binding. Proc Natl Acad Sci U S A 116(14): 6828-6835.
O’Leary TS, Snyder J, Sadayappan S, Day SM, Previs MJ (2019) MYBPC3 truncation mutations enhance actomyosin contractile mechanics in human hypertrophic cardiomyopathy. J Mol Cell Cardiol 127: 165-173.
Lin BL, Li A, Mun JY, Previs MJ, Previs SB, Campbell SG, Dos Remedios CG, Tombe PP, Craig R, Warshaw DM, Sadayappan S (2018) Skeletal myosin binding protein-C isoforms regulate thin filament activity in a Ca2+-dependent manner. Sci Rep 8(1): 2604.
Bookwalter CS, Tay CL, McCrorie R, Previs MJ, Lu H, Krementsova EB, Fagnant PM, Baum J, Trybus KM (2017) Reconstitution of the core of the malaria parasite glideosome with recombinant Plasmodium class XIV myosin A and Plasmodium actin. J Biol Chem 292(47): 19290-19303.
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.