Personal History:I received my B.S. in 2005 from Wake Forest University, where I began my study of biomechanics and muscle physiology. I did my graduate work in the Department of Biochemistry at the University of Maryland School of Medicine from 2005-2009, where I studied skeletal muscle cellular biology and excitation-contraction coupling under Dr. Martin Schneider.
Upon completion of my graduate studies, I switched my focus to the heart and joined the lab of Dr. W.J. Lederer, then part of the University of Maryland Biotechnology Institute (UMBI). I served as a post-doc in the Lederer lab from 2009-2012, where I began to investigate how the mechanical stretch of heart cells affects signaling by reactive oxygen species (ROS) and calcium ions. I joined the Dept. of Physiology as an Assistant Professor in 2012.
Research Interests:I am primarily interested in how the mechanical stress that is imposed on heart cells during the cardiac cycle affects cellular signaling, particularly in regards to intracellular calcium homeostasis and ROS/redox signaling. Our group recently discovered that when a heart cell is stretch, as occurs during diastolic filling of the ventricles with blood, reactive oxygen species are rapidly generated, and these ROS affect the activity of calcium release channels in the sarcoplasmic reticulum, the ryanodine receptors. This stretch-dependent mechanism regulates cardiac excitation-contraction coupling, and under certain conditions may trigger calcium-dependent arrhythmias. We are actively investigating how this unique mechano-transduction mechanism affects normal and pathological calcium signaling in heart and other tissues, particularly skeletal and smooth muscle.
Lab Techniques and Equipment:We have developed novel technologies to attach and stretch intact, freshly isolated cardiomyocytes using a biological adhesive, MyoTak™. We combine this technique with high-speed confocal microscopy, patch clamp electrophysiology, and mechanical measurements of contractile force to simultaneously investigate the homeostatic interplay between cell length, electrical activity, EC coupling, and contractility, all in a tightly controlled environment.
The lab is also equipped for investigation of ex-vivo whole heart imaging and electrophysiology, immunohistochemistry, super-resolution imaging, and molecular biology. We use adeno-associated viral transfection of young rodents to manipulate transcript and protein expression, and combine this with the study of transgenic mice to isolate the influence of specific proteins on stretch-dependent signaling in heart.
Messier SP, Mihalko S, Loeser RF, Legault C, Jolla J, Pfruender J, Prosser B, Adrian A, Williamson JD. (2007) Glucosamine/chondroitin combined with exercise for the treatment of knee osteoarthritis: a preliminary study. Osteoarthritis Cartilage. Nov;15(11):1256-66
Prosser BL, Wright NT, Hernández-Ochoa EH, Varney KM, Liu Y, Olojo RO, Zimmer DB, Weber DJ, Schneider MF. (2008) S100A1 binds to the calmodulin binding site of ryanodine receptor and modulates skeletal muscle excitation-contraction coupling. J Biol Chem. Feb 22;283(8):5046-57.
Wright NT, Prosser BL, Varney KM, Zimmer DB, Schneider MF, Weber DJ. (2008) S100A1 and calmodulin compete for the same binding site on ryanodine receptor. J Biol Chem. Sep 26;283(39):26676-83. PMCID: PMC2546546
Prosser BL, Hernández-Ochoa EH, Zimmer DB, Schneider MF. (2009) The Qy component of intra-membrane charge movement is present in mammalian muscle fibres, but suppressed in the absence of S100A1. J Physiol. Sep 15;587(Pt 18):4523-41. PMCID: PMC2766655
Prosser BL, Hernández-Ochoa EH, Zimmer DB, Schneider MF. (2009) Simultaneous recording of intra-membrane charge movement components and calcium release in wild type and S100A1-/- muscle fibres. J Physiol. Sep 15;587(Pt 18):4543-59. PMCID: PMC2766656
Hernández-Ochoa EH, Prosser BL, Wright NT, Weber DJ, Schneider MF. (2009) Augmentation of Cav1 channel currents and action potential duration after uptake of S100A1 in sympathetic ganglion neurons. Am J Physiol Cell Physiol. Oct;297(4):C955-70. PMCID: PMC2770745
Prosser BL, Ward CW, Lederer WJ. (2010) Subcellular Ca2+ signaling in the heart: the role of ryanodine receptor sensitivity. J Gen Physiol. Aug; 136(2):135-42. PMCID: PMC2912070
Prosser BL, Hernandez-Ochoa E, Lovering RM, Andronache Z, Zimmer DB, Melzer W, Schneider MF. (2010) S100A1 promotes action potential-initiated calcium release flux and force production in skeletal muscle. Am J Physiol Cell Physiol. Aug 4 Epub PMCID: PMC2980316
Yamaguchi N, Prosser BL*, Ghassemi F, Xu L, Pasek D, Eu J, Hernandez-Ochoa E, Cannon B, Wilder P, Lovering R, Weber D, Melzer W, Schneider M, Meissner G. (2011) Modulation of sarcoplasmic reticulum Ca2+ release in skeletal muscle expressing ryanodine receptor impaired in regulation by calmodulin and S100A1. Am J Physiol Cell Physiol. Feb 2. [Epub ahead of print] * Denotes co-first authorship PMCID: PMC3093939
Lovering RM, O'Neill A, Muriel JM, Prosser BL, Strong J, Bloch RJ. (2011) Physiology, Structure, and Susceptibility to Injury of Skeletal Muscle in Mice Lacking Keratin 19-Based and Desmin-Based Intermediate Filaments. Am J Physiol Cell Physiol. Jan 5. [Epub ahead of print]. PMCID: PMC3074621
Prosser BL, Hernández-Ochoa EH, Schneider MF. (2011) S100A1 and calmodulin regulation of ryanodine receptor in striated muscle. Cell Calcium. Jul 22 Epub. PMCID: PMC3185186
Prosser BL, Ward CW, Lederer WJ. (2011) X-ROS signaling: Rapid mechano-chemo transduction in heart. Science. 333, 1440, 9 Sept.
Khairallah RJ, Shi G, Sbrana F, Prosser BL, Borroto C, Mazaitis MJ, Hoffman EP, Mahurkar A, Sachys F, Sun Y, Chen YW, Raiteri R, Lederer WJ, Dorsey SG, Ward CW. (2012) Microtubules underlie dysfunction in Duchenne muscular dystrophy. Sci. Signal. 5, ra56.
Prosser BL, Khairallah RJ, Ziman AP, Ward CW, Lederer WJ. (2012) X-ROS signaling in heart and skeletal muscle: stretch-dependent local ROS regulates [Ca2+]i. J. Mol Cell Cardiol. Dec 6.
Prosser BL, Ward CW, Lederer WJ. (2013) X-ROS signaling is enhanced and graded by cyclic cardiomyocyte stretch. Cardiovascular Research. Epub Mar 21. PMCID: PMC3633162
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