Biomedical Research Education & Training
Faculty Member

Tyska, Matthew John, Ph.D.
Professor of Cell & Developmental Biology

Lab Url:

Phone Number: (615) 936-5461

Email Address:

Tyska, Matthew's picture
Academic history
B.S., University of Notre Dame
Ph.D., University of Vermont
Postdoctoral Fellow, Yale University

Office Address   Mailing Address

3154 MRB III

3154 MRB III 465 21st Ave South 8240

Research Keywords
epithelial cell biology, biophysics, biochemistry, motor protein, actin cytoskeleton, motility, cell polarity, knockout mouse, cell culture, proteomics, confocal, TIRF, deconvolution, super-resolution, microscopy, live cell imaging, fluorescence, optical tweezers.,Bacteria,Biochemistry,Developmental biology,Enzyme action,Infectious disease,Knockout,Mass spectroscopy,Membrane,Microbiology,Mouse,Mutation,Pathology,Protein Structure,Proteomics ,Bacteria,Biochemistry,Developmental biology,Enzyme action,Infectious disease,Knockout,Mass spectroscopy,Membrane,Microbiology,Mouse,Mutation,Pathology,Protein Structure,Proteomics

Research Description
Research in our laboratory is focused on investigating the architecture, dynamics, and function of the actin cytoskeleton. The context for our studies is the brush border: an array of actin-based protrusions known as microvilli, which extend from the surface of polarized epithelial cells. In the gut, the brush border serves as the sole site of nutrient absorption and a barrier to micro-organisms that reside in the lumenal space. Using an approach that combines biophysics, biochemistry, and cell biology, we are currently studying mechanisms that control microvillar dynamics, morphology, and function. We have also begun to dissect the mechanism of microvillar assembly, which was jumpstarted by our recent elucidation of the entire brush border proteome. A broad long-term goal is to develop our understanding of molecules and pathways that may be perturbed in GI diseases characterized by loss of the brush border (e.g. enteropathogenic E. coli infection, celiac disease, and microvillus inclusion disease).

Crawley, SW, Mooseker, MS, Tyska, MJ. Shaping the intestinal brush border. J Cell Biol, 207(4), 441-51, 2014

Crawley, SW, Shifrin, DA, Grega-Larson, NE, McConnell, RE, Benesh, AE, Mao, S, Zheng, Y, Zheng, QY, Nam, KT, Millis, BA, Kachar, B, Tyska, MJ. Intestinal brush border assembly driven by protocadherin-based intermicrovillar adhesion. Cell, 157(2), 433-46, 2014

G??rard, A, Patino-Lopez, G, Beemiller, P, Nambiar, R, Ben-Aissa, K, Liu, Y, Totah, FJ, Tyska, MJ, Shaw, S, Krummel, MF. Detection of rare antigen-presenting cells through T cell-intrinsic meandering motility, mediated by Myo1g. Cell, 158(3), 492-505, 2014

Knowles, BC, Roland, JT, Krishnan, M, Tyska, MJ, Lapierre, LA, Dickman, PS, Goldenring, JR, Shub, MD. Myosin Vb uncoupling from RAB8A and RAB11A elicits microvillus inclusion disease. J Clin Invest, 124(7), 2947-62, 2014

Knowles, BC, Tyska, MJ, Goldenring, JR. Apical vesicle trafficking takes center stage in neonatal enteropathies. Gastroenterology, 147(1), 15-7, 2014

Mazerik, JN, Kraft, LJ, Kenworthy, AK, Tyska, MJ. Motor and tail homology 1 (Th1) domains antagonistically control myosin-1 dynamics. Biophys J, 106(3), 649-58, 2014

Shifrin, DA, Crawley, SW, Grega-Larson, NE, Tyska, MJ. Dynamics of brush border remodeling induced by enteropathogenic E. coli. Gut Microbes, 5(4), 504-16, 2014

Hoshino, D, Kirkbride, KC, Costello, K, Clark, ES, Sinha, S, Grega-Larson, N, Tyska, MJ, Weaver, AM. Exosome secretion is enhanced by invadopodia and drives invasive behavior. Cell Rep, 5(5), 1159-68, 2013

Shifrin, DA, Beckler, MD, Coffey, RJ, Tyska, MJ. Extracellular vesicles: communication, coercion, and conditioning. Mol Biol Cell, 24(9), 1253-9, 2013

Benesh, AE, Fleming, JT, Chiang, C, Carter, BD, Tyska, MJ. Expression and localization of myosin-1d in the developing nervous system. Brain Res, 1440, 9-22, 2012

Liu, Y, Belkina, NV, Park, C, Nambiar, R, Loughhead, SM, Patino-Lopez, G, Ben-Aissa, K, Hao, JJ, Kruhlak, MJ, Qi, H, von Andrian, UH, Kehrl, JH, Tyska, MJ, Shaw, S. Constitutively active ezrin increases membrane tension, slows migration, and impedes endothelial transmigration of lymphocytes in vivo in mice. Blood, 119(2), 445-53, 2012

Mazerik, JN, Tyska, MJ. Myosin-1A targets to microvilli using multiple membrane binding motifs in the tail homology 1 (TH1) domain. J Biol Chem, 287(16), 13104-15, 2012

Pyrpassopoulos, S, Feeser, EA, Mazerik, JN, Tyska, MJ, Ostap, EM. Membrane-bound myo1c powers asymmetric motility of actin filaments. Curr Biol, 22(18), 1688-92, 2012

Shifrin, DA, McConnell, RE, Nambiar, R, Higginbotham, JN, Coffey, RJ, Tyska, MJ. Enterocyte microvillus-derived vesicles detoxify bacterial products and regulate epithelial-microbial interactions. Curr Biol, 22(7), 627-31, 2012

Shifrin, DA, Tyska, MJ. Ready-aim-fire into the lumen: A new role for enterocyte microvilli in gut host defense. Gut Microbes, 3(5), 2012

Higginbotham, JN, Demory Beckler, M, Gephart, JD, Franklin, JL, Bogatcheva, G, Kremers, GJ, Piston, DW, Ayers, GD, McConnell, RE, Tyska, MJ, Coffey, RJ. Amphiregulin exosomes increase cancer cell invasion. Curr Biol, 21(9), 779-86, 2011 PMCID:3131266

McConnell, RE, Benesh, AE, Mao, S, Tabb, DL, Tyska, MJ. Proteomic analysis of the enterocyte brush border. Am J Physiol Gastrointest Liver Physiol, 2011

Pyburn, TM, Bensing, BA, Xiong, YQ, Melancon, BJ, Tomasiak, TM, Ward, NJ, Yankovskaya, V, Oliver, KM, Cecchini, G, Sulikowski, GA, Tyska, MJ, Sullam, PM, Iverson, TM. A structural model for binding of the serine-rich repeat adhesin GspB to host carbohydrate receptors. PLoS Pathog, 7(7), e1002112, 2011 PMCID:3131266

Benesh, AE, Nambiar, R, McConnell, RE, Mao, S, Tabb, DL, Tyska, MJ. Differential localization and dynamics of class I myosins in the enterocyte microvillus. Mol Biol Cell, 21(6), 970-8, 2010 PMCID:2836977

McConnell, RE, Tyska, MJ. Leveraging the membrane - cytoskeleton interface with myosin-1. Trends Cell Biol, 20(7), 418-26, 2010 PMCID:2881245

Nambiar, R, McConnell, RE, Tyska, MJ. Myosin motor function: the ins and outs of actin-based membrane protrusions. Cell Mol Life Sci, 67(8), 1239-54, 2010 PMCID:2881245

Tyska, MJ, Nambiar, R. Myosin-1a: A motor for microvillar membrane movement and mechanics. Commun Integr Biol, 3(1), 64-6, 2010 PMCID:2881245

McConnell, RE, Higginbotham, JN, Shifrin, DA, Tabb, DL, Coffey, RJ, Tyska, MJ. The enterocyte microvillus is a vesicle-generating organelle. J Cell Biol, 185(7), 1285-98, 2009 PMCID:2712962

Nambiar, R, McConnell, RE, Tyska, MJ. Control of cell membrane tension by myosin-I. Proc Natl Acad Sci U S A, 106(29), 11972-7, 2009 PMCID:2715533

Wang, J, Qin, R, Ma, Y, Wu, H, Peters, H, Tyska, M, Shaheen, NJ, Chen, X. Differential gene expression in normal esophagus and Barrett''s esophagus. J Gastroenterol, 2009

Yengo, CM, Ananthanarayanan, SK, Brosey, CA, Mao, S, Tyska, MJ. Human deafness mutation E385D disrupts the mechanochemical coupling and subcellular targeting of myosin-1a. Biophys J, 94(2), L5-7, 2008 PMCID:2157235

McConnell, RE, Tyska, MJ. Myosin-1a powers the sliding of apical membrane along microvillar actin bundles. J Cell Biol, 177(4), 671-81, 2007 PMCID:2064212

O''Connell, CB, Tyska, MJ, Mooseker, MS. Myosin at work: motor adaptations for a variety of cellular functions. Biochim Biophys Acta, 1773(5), 615-30, 2007

Tyska, MJ, Mackey, AT, Huang, JD, Copland, NG, Jenkins, NA, Mooseker, MS. Myosin-1a Is Critical for Normal Brush Border Structure and Composition. Mol Biol Cell, 16, 2443-2457, 2005 PMCID:1087248

Tyska, M J, Mooseker, M S. A role for myosin-1A in the localization of a brush border disaccharidase. J Cell Biol, 165(3), 395-405, 2004 PMCID:2172191

Tyska, M J, Mooseker, M S. Myosin-V motility: these levers were made for walking. Trends Cell Biol, 13(9), 447-51, 2003

*Post, P L, *Tyska, M J, OConnell, C B, Johung, K, Hayward, A, Mooseker, M S. Myosin-IXb is a single-headed and processive motor. J Biol Chem, 277(14), 11679-83, 2002 *These authors contributed equally to this work.

Tyska, M J, Mooseker, M S. MYO1A (brush border myosin I) dynamics in the brush border of LLC-PK1-CL4 cells. Biophys J, 82(4), 1869-83, 2002 PMCID:1301984

Tyska, M J, Warshaw, D M. The myosin power stroke. Cell Motil Cytoskeleton, 51(1), 1-15, 2002

Reck-Peterson, S L, Tyska, M J, Novick, P J, Mooseker, M S. The yeast class V myosins, Myo2p and Myo4p, are nonprocessive actin-based motors. J Cell Biol, 153(5), 1121-6, 2001 PMCID:2174330

Palmiter, K A, Tyska, M J, Haeberle, J R, Alpert, N R, Fananapazir, L, Warshaw, D M. R403Q and L908V mutant beta-cardiac myosin from patients with familial hypertrophic cardiomyopathy exhibit enhanced mechanical performance at the single molecule level. J Muscle Res Cell Motil, 21(7), 609-20, 2000

Tyska, M J, Hayes, E, Giewat, M, Seidman, C E, Seidman, J G, Warshaw, D M. Single-molecule mechanics of R403Q cardiac myosin isolated from the mouse model of familial hypertrophic cardiomyopathy. Circ Res, 86(7), 737-44, 2000

Warshaw, D M, Guilford, W H, Freyzon, Y, Krementsova, E, Palmiter, K A, Tyska, M J, Baker, J E, Trybus, K M. The light chain binding domain of expressed smooth muscle heavy meromyosin acts as a mechanical lever. J Biol Chem, 275(47), 37167-72, 2000

Yamashita, H, Tyska, M J, Warshaw, D M, Lowey, S, Trybus, K M. Functional consequences of mutations in the smooth muscle myosin heavy chain at sites implicated in familial hypertrophic cardiomyopathy. J Biol Chem, 275(36), 28045-52, 2000

Palmiter, K A, Tyska, M J, Dupuis, D E, Alpert, N R, Warshaw, D M. Kinetic differences at the single molecule level account for the functional diversity of rabbit cardiac myosin isoforms. J Physiol, 519 Pt 3, 669-78, 1999 PMCID:2269540

Tyska, M J, Dupuis, D E, Guilford, W H, Patlak, J B, Waller, G S, Trybus, K M, Warshaw, D M, Lowey, S. Two heads of myosin are better than one for generating force and motion. Proc Natl Acad Sci U S A, 96(8), 4402-7, 1999 PMCID:16344

Lauzon, A M, Tyska, M J, Rovner, A S, Freyzon, Y, Warshaw, D M, Trybus, K M. A 7-amino-acid insert in the heavy chain nucleotide binding loop alters the kinetics of smooth muscle myosin in the laser trap. J Muscle Res Cell Motil, 19(8), 825-37, 1998

Postdoctoral Position Available

Postdoctoral Position Details
A postdoctoral position is available to investigate the function of actin-based motor proteins (myosins) using state-of-the-art cell biological and biophysical approaches. Potential projects include but are not limited to: 1) the mechanical characterization of myosin motors in vitro and in living cells using optical trapping technology, 2) studying the dynamics of the actin cytoskeleton and associated myosins using the latest live cell imaging technologies, and 3) applying advanced proteomic approaches to define the composition of native myosin/cargo complexes and F-actin arrays. Previous experience with cell culture techniques, molecular biology (cloning/mutagenesis), protein biochemistry (expression/purification), and light microscopy is very important. Interested candidates should email a copy of their CV and the names of three references to

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