Matthew John Tyska, Ph.D.

Professor

matthew.tyska@vanderbilt.edu

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Faculty Appointments
Professor of Cell and Developmental Biology
Education
Ph.D., Molecular Physiology and Biophysics, University of Vermont, Burlington, VermontM.S., Exercise Physiology, University of Wyoming, Laramie, WyomingB.S., Biological Sciences, University of Notre Dame, South Bend, Indiana
Office Address
3154 MRB III
465 21st Ave South
Nashville, TN 8240
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).
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
Publications
Grega-Larson NE, Crawley SW, Erwin AL, Tyska MJ. Cordon bleu promotes the assembly of brush border microvilli. Mol. Biol. Cell [print-electronic]. 2015 Nov 11/1/2015; 26(21): 3803-15. PMID: 26354418, PMCID: PMC4626065, PII: mbc.E15-06-0443, DOI: 10.1091/mbc.E15-06-0443, ISSN: 1939-4586.

Crawley SW, Mooseker MS, Tyska MJ. Shaping the intestinal brush border. J. Cell Biol. 2014 Nov 11/24/2014; 207(4): 441-51. PMID: 25422372, PMCID: PMC4242837, PII: jcb.201407015, DOI: 10.1083/jcb.201407015, ISSN: 1540-8140.

Gérard 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. 2014 Jul 7/31/2014; 158(3): 492-505. PMID: 25083865, PMCID: PMC4119593, PII: S0092-8674(14)00802-2, DOI: 10.1016/j.cell.2014.05.044, ISSN: 1097-4172.

Knowles BC, Tyska MJ, Goldenring JR. Apical vesicle trafficking takes center stage in neonatal enteropathies [editorial]. Gastroenterology. 2014 Jul; 147(1): 15-7. PMID: 24954664, PII: S0016-5085(14)00676-3, DOI: 10.1053/j.gastro.2014.05.028, ISSN: 1528-0012.

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 [print-electronic]. 2014 Jul; 124(7): 2947-62. PMID: 24892806, PMCID: PMC4071383, PII: 71651, DOI: 10.1172/JCI71651, ISSN: 1558-8238.

Shifrin DA, Crawley SW, Grega-Larson NE, Tyska MJ. Dynamics of brush border remodeling induced by enteropathogenic E. coli. Gut Microbes [print-electronic]. 2014 Jul 7/1/2014; 5(4): 504-16. PMID: 25076126, PII: 32084, DOI: 10.4161/gmic.32084, ISSN: 1949-0984.

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. 2014 Apr 4/10/2014; 157(2): 433-46. PMID: 24725409, PMCID: PMC3992856, PII: S0092-8674(14)00215-3, DOI: 10.1016/j.cell.2014.01.067, ISSN: 1097-4172.

Mazerik JN, Kraft LJ, Kenworthy AK, Tyska MJ. Motor and tail homology 1 (Th1) domains antagonistically control myosin-1 dynamics. Biophys. J. 2014 Feb 2/4/2014; 106(3): 649-58. PMID: 24507605, PMCID: PMC3944834, PII: S0006-3495(14)00012-5, DOI: 10.1016/j.bpj.2013.12.038, ISSN: 1542-0086.

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 [print-electronic]. 2013 Dec 12/12/2013; 5(5): 1159-68. PMID: 24290760, PMCID: PMC3873329, PII: S2211-1247(13)00652-9, DOI: 10.1016/j.celrep.2013.10.050, ISSN: 2211-1247.

Shifrin DA, Demory Beckler M, Coffey RJ, Tyska MJ. Extracellular vesicles: communication, coercion, and conditioning. Mol. Biol. Cell. 2013 May; 24(9): 1253-9. PMID: 23630232, PMCID: PMC3639038, PII: 24/9/1253, DOI: 10.1091/mbc.E12-08-0572, ISSN: 1939-4586.

Pyrpassopoulos S, Feeser EA, Mazerik JN, Tyska MJ, Ostap EM. Membrane-bound myo1c powers asymmetric motility of actin filaments. Curr. Biol [print-electronic]. 2012 Sep 9/25/2012; 22(18): 1688-92. PMID: 22863317, PMCID: PMC3461085, PII: S0960-9822(12)00745-2, DOI: 10.1016/j.cub.2012.06.069, ISSN: 1879-0445.

Shifrin DA, Tyska MJ. Ready…aim…fire into the lumen: a new role for enterocyte microvilli in gut host defense. Gut Microbes [print-electronic]. 2012 Sep; 3(5): 460-2. PMID: 22825496, PMCID: PMC3466500, PII: 21247, DOI: 10.4161/gmic.21247, ISSN: 1949-0984.

Mazerik JN, Tyska MJ. Myosin-1A targets to microvilli using multiple membrane binding motifs in the tail homology 1 (TH1) domain. J. Biol. Chem [print-electronic]. 2012 Apr 4/13/2012; 287(16): 13104-15. PMID: 22367206, PMCID: PMC3339983, PII: M111.336313, DOI: 10.1074/jbc.M111.336313, ISSN: 1083-351X.

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 [print-electronic]. 2012 Apr 4/10/2012; 22(7): 627-31. PMID: 22386311, PMCID: PMC3326206, PII: S0960-9822(12)00171-6, DOI: 10.1016/j.cub.2012.02.022, ISSN: 1879-0445.

Benesh AE, Fleming JT, Chiang C, Carter BD, Tyska MJ. Expression and localization of myosin-1d in the developing nervous system. Brain Res [print-electronic]. 2012 Feb 2/27/2012; 1440: 9-22. PMID: 22284616, PMCID: PMC3278530, PII: S0006-8993(11)02323-7, DOI: 10.1016/j.brainres.2011.12.054, ISSN: 1872-6240.

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 [print-electronic]. 2012 Jan 1/12/2012; 119(2): 445-53. PMID: 22106344, PMCID: PMC3257010, PII: blood-2011-07-368860, DOI: 10.1182/blood-2011-07-368860, ISSN: 1528-0020.

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 [print-electronic]. 2011 Jul; 7(7): e1002112. PMID: 21765814, PMCID: PMC3131266, PII: PPATHOGENS-D-11-00123, DOI: 10.1371/journal.ppat.1002112, ISSN: 1553-7374.

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 [print-electronic]. 2011 May 5/10/2011; 21(9): 779-86. PMID: 21514161, PMCID: PMC3417320, PII: S0960-9822(11)00347-2, DOI: 10.1016/j.cub.2011.03.043, ISSN: 1879-0445.

McConnell RE, Benesh AE, Mao S, Tabb DL, Tyska MJ. Proteomic analysis of the enterocyte brush border. Am. J. Physiol. Gastrointest. Liver Physiol [print-electronic]. 2011 May; 300(5): G914-26. PMID: 21330445, PMCID: PMC3094140, PII: ajpgi.00005.2011, DOI: 10.1152/ajpgi.00005.2011, ISSN: 1522-1547.

McConnell RE, Tyska MJ. Leveraging the membrane - cytoskeleton interface with myosin-1. Trends Cell Biol [print-electronic]. 2010 Jul; 20(7): 418-26. PMID: 20471271, PMCID: PMC2897960, PII: S0962-8924(10)00077-2, DOI: 10.1016/j.tcb.2010.04.004, ISSN: 1879-3088.

Nambiar R, McConnell RE, Tyska MJ. Myosin motor function: the ins and outs of actin-based membrane protrusions. Cell. Mol. Life Sci [print-electronic]. 2010 Apr; 67(8): 1239-54. PMID: 20107861, PMCID: PMC3095969, DOI: 10.1007/s00018-009-0254-5, ISSN: 1420-9071.

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 [print-electronic]. 2010 Mar 3/15/2010; 21(6): 970-8. PMID: 20089841, PMCID: PMC2836977, PII: E09-07-0638, DOI: 10.1091/mbc.E09-07-0638, ISSN: 1939-4586.

Tyska MJ, Nambiar R. Myosin-1a: A motor for microvillar membrane movement and mechanics. Commun Integr Biol. 2010 Jan; 3(1): 64-6. PMID: 20539787, PMCID: PMC2881245, ISSN: 1942-0889.

Nambiar R, McConnell RE, Tyska MJ. Control of cell membrane tension by myosin-I. Proc. Natl. Acad. Sci. U.S.A [print-electronic]. 2009 Jul 7/21/2009; 106(29): 11972-7. PMID: 19574460, PMCID: PMC2715533, PII: 0901641106, DOI: 10.1073/pnas.0901641106, ISSN: 1091-6490.

McConnell RE, Higginbotham JN, Shifrin DA, Tabb DL, Coffey RJ, Tyska MJ. The enterocyte microvillus is a vesicle-generating organelle. J. Cell Biol. 2009 Jun 6/29/2009; 185(7): 1285-98. PMID: 19564407, PMCID: PMC2712962, PII: jcb.200902147, DOI: 10.1083/jcb.200902147, ISSN: 1540-8140.

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 [print-electronic]. 2009; 44(9): 897-911. PMID: 19468668, PMCID: PMC3811010, DOI: 10.1007/s00535-009-0082-2, ISSN: 1435-5922.

Yengo CM, Ananthanarayanan SK, Brosey CA, Mao S, Tyska MJ. Human deafness mutation E385D disrupts the mechanochemical coupling and subcellular targeting of myosin-1a [letter]. Biophys. J [print-electronic]. 2008 Jan 1/15/2008; 94(2): L5-7. PMID: 17981900, PMCID: PMC2157235, PII: S0006-3495(08)70708-2, DOI: 10.1529/biophysj.107.122689, ISSN: 1542-0086.

McConnell RE, Tyska MJ. Myosin-1a powers the sliding of apical membrane along microvillar actin bundles. J. Cell Biol [print-electronic]. 2007 May 5/21/2007; 177(4): 671-81. PMID: 17502425, PMCID: PMC2064212, PII: jcb.200701144, DOI: 10.1083/jcb.200701144, ISSN: 0021-9525.

O'Connell CB, Tyska MJ, Mooseker MS. Myosin at work: motor adaptations for a variety of cellular functions. Biochim. Biophys. Acta [print-electronic]. 2007 May; 1773(5): 615-30. PMID: 16904206, PII: S0167-4889(06)00153-4, DOI: 10.1016/j.bbamcr.2006.06.012, ISSN: 0006-3002.

Tyska MJ, Mackey AT, Huang JD, Copeland NG, Jenkins NA, Mooseker MS. Myosin-1a is critical for normal brush border structure and composition. Mol. Biol. Cell [print-electronic]. 2005 May; 16(5): 2443-57. PMID: 15758024, PMCID: PMC1087248, PII: E04-12-1116, DOI: 10.1091/mbc.E04-12-1116, ISSN: 1059-1524.

Tyska MJ, Mooseker MS. A role for myosin-1A in the localization of a brush border disaccharidase. J. Cell Biol. 2004 May 5/10/2004; 165(3): 395-405. PMID: 15138292, PMCID: PMC2172191, PII: jcb.200310031, DOI: 10.1083/jcb.200310031, ISSN: 0021-9525.

Tyska MJ, Mooseker MS. Myosin-V motility: these levers were made for walking. Trends Cell Biol. 2003 Sep; 13(9): 447-51. PMID: 12946621, PII: S0962892403001727, ISSN: 0962-8924.

Post PL, Tyska MJ, O'Connell CB, Johung K, Hayward A, Mooseker MS. Myosin-IXb is a single-headed and processive motor. J. Biol. Chem [print-electronic]. 2002 Apr 4/5/2002; 277(14): 11679-83. PMID: 11801597, PII: M111173200, DOI: 10.1074/jbc.M111173200, ISSN: 0021-9258.

Tyska MJ, Mooseker MS. MYO1A (brush border myosin I) dynamics in the brush border of LLC-PK1-CL4 cells. Biophys. J. 2002 Apr; 82(4): 1869-83. PMID: 11916846, PMCID: PMC1301984, PII: S0006-3495(02)75537-9, DOI: 10.1016/S0006-3495(02)75537-9, ISSN: 0006-3495.

Tyska MJ, Warshaw DM. The myosin power stroke. Cell Motil. Cytoskeleton. 2002 Jan; 51(1): 1-15. PMID: 11810692, PII: 10.1002/cm.10014, DOI: 10.1002/cm.10014, ISSN: 0886-1544.

Reck-Peterson SL, Tyska MJ, Novick PJ, Mooseker MS. The yeast class V myosins, Myo2p and Myo4p, are nonprocessive actin-based motors. J. Cell Biol. 2001 May 5/28/2001; 153(5): 1121-6. PMID: 11381095, PMCID: PMC2174330, ISSN: 0021-9525.

Warshaw DM, Guilford WH, Freyzon Y, Krementsova E, Palmiter KA, Tyska MJ, Baker JE, Trybus KM. The light chain binding domain of expressed smooth muscle heavy meromyosin acts as a mechanical lever. J. Biol. Chem. 2000 Nov 11/24/2000; 275(47): 37167-72. PMID: 10945998, PII: M006438200, DOI: 10.1074/jbc.M006438200, ISSN: 0021-9258.

Yamashita H, Tyska MJ, Warshaw DM, Lowey S, Trybus KM. Functional consequences of mutations in the smooth muscle myosin heavy chain at sites implicated in familial hypertrophic cardiomyopathy. J. Biol. Chem. 2000 Sep 9/8/2000; 275(36): 28045-52. PMID: 10882745, PII: M005485200, DOI: 10.1074/jbc.M005485200, ISSN: 0021-9258.

Tyska MJ, Hayes E, Giewat M, Seidman CE, Seidman JG, Warshaw DM. Single-molecule mechanics of R403Q cardiac myosin isolated from the mouse model of familial hypertrophic cardiomyopathy. Circ. Res. 2000 Apr 4/14/2000; 86(7): 737-44. PMID: 10764406, ISSN: 1524-4571.

Palmiter KA, Tyska MJ, Haeberle JR, Alpert NR, Fananapazir L, Warshaw DM. 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. 2000; 21(7): 609-20. PMID: 11227787, ISSN: 0142-4319.

Palmiter KA, Tyska MJ, Dupuis DE, Alpert NR, Warshaw DM. Kinetic differences at the single molecule level account for the functional diversity of rabbit cardiac myosin isoforms. J. Physiol. (Lond.). 1999 Sep 9/15/1999; 519 Pt 3: 669-78. PMID: 10457082, PMCID: PMC2269540, PII: PHY_9413, ISSN: 0022-3751.

Tyska MJ, Dupuis DE, Guilford WH, Patlak JB, Waller GS, Trybus KM, Warshaw DM, Lowey S. Two heads of myosin are better than one for generating force and motion. Proc. Natl. Acad. Sci. U.S.A. 1999 Apr 4/13/1999; 96(8): 4402-7. PMID: 10200274, PMCID: PMC16344, ISSN: 0027-8424.

Lauzon AM, Tyska MJ, Rovner AS, Freyzon Y, Warshaw DM, Trybus KM. 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. 1998 Nov; 19(8): 825-37. PMID: 10047983, ISSN: 0142-4319.

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 matthew.tyska@vanderbilt.edu.