Professor Steve Winder

School of Biosciences

Emeritus Professor

Director of Recruitment and International Relations

s.winder@sheffield.ac.uk

B206, Firth Court

Full contact details

Professor Steve Winder
School of Biosciences
B206
Firth Court
Western Bank
Sheffield
S10 2TN

Profile

Brief career history

2005-Present: Professor of Molecular Cell Biology, School of Biosciences, University of Sheffield
2003-2005: Reader, Department of Biomedical Science, University of Sheffield
1999-2003: Lecturer (99-01) Reader (02-03), University of Glasgow
1995-1999: Wellcome Trust Fellow, ICMB, University of Edinburgh
1992-1995: Staff Scientist, Laboratory of Molecular Biology, Cambridge - Advisor, Jake Kendrick-Jones
1988-1992: Postdoctoral Fellow, Biochemistry, University of Calgary, Advisor - Mike Walsh.
1984-1988: PhD, University of Reading, Supervisor - Isabel Forsyth

Research interests

Regulation of dystroglycan function in muscular dystrophy and cancer

The laminin binding protein dystroglycan plays multiple roles in cell adhesion, signalling and membrane cytoskeleton stability. Perturbation of dystroglycan function underlies several muscular dystrophies and is also a secondary consequence of adenocarcinoma progression.

Changes to the post-translational modification of dystroglycan are crucial in directing the associations, cellular localisation and ultimately degradation of dystroglycan.

Our aim is to elucidate the mechanisms and consequences of these post-translational modifications in order to better understand dystroglycan function and to identify potential therapeutic targets for the treatment of muscular dystrophy or cancer.

We employ in vitro, in/ex vivo fish and mouse genetic models with clinically relevant archival tissue samples or immortalised cell lines. Dystroglycan function is dissected through the use of molecular cell biology approaches, and potential therapeutic targets are assessed in vitro and in vivo.

Recently we have developed a novel therapeutic approach for the treatment of Duchenne muscular dystrophy using inhibitors of tyrosine phosphorylation and proteasomal degradation. Through the use of zebrafish screening and phenotypic analysis in mdx mice and human DMD myoblasts we are in the process of validating the potential for repurposed drugs as a precursor to initiating clinical trials.

Physiological analysis is carried out I collaboration with Nic Wells at the RVC London.

In vitro models of prostate cancer have revealed a role for the post-translational proteolytic processing and nuclear targeting of dystroglycan.

Current efforts are centred around characterising a role as part of the LINC complex in the inner nuclear membrane. These studies form part of an ongoing collaboration with Bulmaro Cisneros, CINVESTAV Mexico City.

Funding

Action Duchenne - Repurposed Cancer Therapeutics as Treatments for DMD
Duchenne UK - Are soy products effective in DMD?
White Rose - The Dystroglycan LINC
Action on Hearing Loss - Dystroglycan function in hearing and hearing loss

Publications

Show: Featured publications All publications

Featured publications

Journal articles

Lipscomb L, Piggott RW, Emmerson T & Winder SJ (2016) Dasatinib as a treatment for Duchenne muscular dystrophy. Human Molecular Genetics, 25(2), 266-274. View this article in WRRO
Martínez-Vieyra IA, Vásquez-Limeta A, González-Ramírez R, Morales-Lázaro SL, Mondragón M, Mondragón R, Ortega A, Winder SJ & Cisneros B (2013) A role for β-dystroglycan in the organization and structure of the nucleus in myoblasts. Biochimica et Biophysica Acta - Molecular Cell Research, 1833(3), 698-711.
Mathew G, Mitchell A, Down JM, Jacobs LA, Hamdy FC, Eaton C, Rosario DJ, Cross SS & Winder SJ (2013) Nuclear targeting of dystroglycan promotes the expression of androgen regulated transcription factors in prostate cancer.. Sci Rep, 3, 2792. View this article in WRRO
Miller G, Moore CJ, Terry R, La riviere T, Mitchell A, Piggott R, Dear TN, Wells DJ & Winder SJ (2012) Preventing phosphorylation of dystroglycan ameliorates the dystrophic phenotype in mdx mouse. Human Molecular Genetics, 21(20), 4508-4520. View this article in WRRO
García‐Aguirre I, Alamillo‐Iniesta A, Rodríguez‐Pérez R, Vélez‐Aguilera G, Amaro‐Encarnación E, Jiménez‐Gutiérrez E, Vásquez‐Limeta A, Samuel Laredo‐Cisneros M, Morales‐Lázaro SL, Tiburcio‐Félix R , Ortega A et al () Enhanced nuclear protein export in premature aging and rescue of the progeria phenotype by modulation of CRM1 activity. Aging Cell. View this article in WRRO

All publications

Journal articles

Gómez-Monsivais WL, Monterrubio-Ledezma F, Huerta-Cantillo J, Mondragon-Gonzalez R, Alamillo-Iniesta A, García-Aguirre I, Azuara-Medina PM, Arguello-García R, Rivera-Monroy JE, Holaska JM , Hernández-Méndez JME et al (2020) The molecular basis and biologic significance of the β-dystroglycan-emerin interaction. International Journal of Molecular Sciences, 21(17).
Mias-Lucquin D, Dos Santos Morais R, Chéron A, Lagarrigue M, Winder SJ, Chenuel T, Pérez J, Appavou M-S, Martel A, Alviset G , Le Rumeur E et al (2020) How the central domain of dystrophin acts to bridge F-actin to sarcolemmal lipids. Journal of Structural Biology, 209(1). View this article in WRRO
Azuara-Medina P, Sandoval-Duarte A, Morales-Lázaro S, Modragón-González R, Vélez-Aguilera G, Gómez-López J, Jiménez-Gutiérrez G, Tiburcio-Félix R, Martínez-Vieyra I, Sánchez R , Längst G et al (2019) The intracellular domain of β-dystroglycan mediates the nucleolar stress response by suppressing UBF transcriptional activity. Cell Death and Disease, 10. View this article in WRRO
Gracida-Jiménez V, Mondragón-González R, Vélez-Aguilera G, Vásquez-Limeta A, Laredo-Cisneros MS, de Dios Gómez-López J, Vaca L, Gourlay SC, Jacobs LA, Winder SJ & Cisneros B (2018) Publisher Correction: Retrograde trafficking of β-dystroglycan from the plasma membrane to the nucleus. Scientific Reports, 8. View this article in WRRO
Vélez-Aguilera G, de Dios Gómez-López J, Jiménez-Gutiérrez GE, Vásquez-Limeta A, Laredo-Cisneros MS, Gómez P, Winder SJ & Cisneros B (2018) Control of nuclear β-dystroglycan content is crucial for the maintenance of nuclear envelope integrity and function. Biochimica et Biophysica Acta - Molecular Cell Research, 1865(2), 406-420. View this article in WRRO
Gracida-Jiménez V, Mondragón-González R, Vélez-Aguilera G, Vásquez-Limeta A, Laredo-Cisneros MS, Gómez-López JDD, Vaca L, Gourlay SC, Jacobs LA, Winder SJ & Cisneros B (2017) Retrograde trafficking of β-dystroglycan from the plasma membrane to the nucleus. Scientific Reports, 7(1). View this article in WRRO
Alonso-Rangel L, Benítez-Guerrero T, Martínez-Vieyra I, Cisneros B, Martínez-Tovar A, Winder SJ & Cerecedo D (2017) A role for dystroglycan in the pathophysiology of acute leukemic cells.. Life Sciences, 182, 1-9. View this article in WRRO
Brown SC & Winder SJ (2017) 220th ENMC workshop: Dystroglycan and the dystroglycanopathies Naarden, The Netherlands, 27–29 May 2016. Neuromuscular Disorders, 27(4). View this article in WRRO
Leocadio D, Mitchell A & Winder SJ (2016) γ‐Secretase Dependent Nuclear Targeting of Dystroglycan. Journal of Cellular Biochemistry, 117(9), 2149-2157. View this article in WRRO
Hoffman E & Winder SJ (2016) A modified wire hanging apparatus for small animal muscle function testing. PLoS Currents. View this article in WRRO
Lipscomb L, Piggott RW, Emmerson T & Winder SJ (2016) Dasatinib as a treatment for Duchenne muscular dystrophy. Human Molecular Genetics, 25(2), 266-274. View this article in WRRO
Escárcega-Tame MA, Martínez-Vieyra I, Alonso-Rangel L, Cisneros B, Winder SJ & Cerecedo D (2015) Dystroglycan Depletion Impairs Actin-Dependent Functions of Differentiated Kasumi-1 Cells. PLOS ONE, 10(12), e0144078-e0144078. View this article in WRRO
Tetlow DJ, Winder SJ & Aïssa C (2015) The synthesis and biological evaluation of a kabiramide C fragment modified with a WH2 consensus actin-binding motif as a potential disruptor of the actin cytoskeleton. Chem. Commun., 52(4), 807-810.
Leiton CV, Aranmolate A, Eyermann C, Menezes MJ, Escobar-Hoyos LF, Husain S, Winder SJ & Colognato H (2015) Laminin promotes metalloproteinase-mediated dystroglycan processing to regulate oligodendrocyte progenitor cell proliferation. Journal of Neurochemistry, 135(3), 522-538.
Cerecedo D, Martínez-Vieyra I, Maldonado-García D, Hernández-González E & Winder SJ (2015) Association of Membrane/Lipid Rafts With the Platelet Cytoskeleton and the Caveolin PY14: Participation in the Adhesion Process. Journal of Cellular Biochemistry, 116(11), 2528-2540.
Tame ME, Martinez-Vieyra I, Cisneros B, Winder SJ & Cerecedo D (2014) Dystroglycan depletion inhibits the functions of differentiated Kasumi-1 cells.. MOLECULAR BIOLOGY OF THE CELL, 25.
Martínez-Zárate AD, Martínez-Vieyra I, Alonso-Rangel L, Cisneros B, Winder SJ & Cerecedo D (2014) Dystroglycan depletion inhibits the functions of differentiated HL-60 cells.. Biochem Biophys Res Commun, 448(3), 274-280.
Singh SM, Bandi S, Winder SJ & Mallela KMG (2014) The actin binding affinity of the utrophin tandem calponin-homology domain is primarily determined by its N-terminal domain. Biochemistry, 53(11), 1801-1809.
Martínez-Vieyra IA, Vásquez-Limeta A, González-Ramírez R, Morales-Lázaro SL, Mondragón M, Mondragón R, Ortega A, Winder SJ & Cisneros B (2013) A role for β-dystroglycan in the organization and structure of the nucleus in myoblasts. Biochimica et Biophysica Acta - Molecular Cell Research, 1833(3), 698-711.
Mathew G, Mitchell A, Down JM, Jacobs LA, Hamdy FC, Eaton C, Rosario DJ, Cross SS & Winder SJ (2013) Nuclear targeting of dystroglycan promotes the expression of androgen regulated transcription factors in prostate cancer.. Sci Rep, 3, 2792. View this article in WRRO
Sarkis J, Víe V, Winder SJ, Renault A, Le Rumeur E & Hubert JF (2013) Resisting sarcolemmal rupture: Dystrophin repeats increase membrane-actin stiffness. FASEB Journal, 27(1), 359-367.
Mitchell A, Mathew G, Jiang T, Hamdy FC, Cross SS, Eaton C & Winder SJ (2013) Dystroglycan function is a novel determinant of tumor growth and behavior in prostate cancer.. Prostate, 73(4), 398-408.
Moore CJ & Winder SJ (2012) The inside and out of dystroglycan post-translational modification.. Neuromuscul Disord, 22(11), 959-965.
Thompson O, Moghraby JS, Ayscough KR & Winder SJ (2012) Depletion of the actin bundling protein SM22/transgelin increases actin dynamics and enhances the tumourigenic phenotypes of cells.. BMC Cell Biol, 13, 1. View this article in WRRO
Miller G, Moore CJ, Terry R, La riviere T, Mitchell A, Piggott R, Dear TN, Wells DJ & Winder SJ (2012) Preventing phosphorylation of dystroglycan ameliorates the dystrophic phenotype in mdx mouse. Human Molecular Genetics, 21(20), 4508-4520. View this article in WRRO
Brown SC & Winder SJ (2012) Dystroglycan and dystroglycanopathies: Report of the 187th ENMC Workshop 11-13 November 2011, Naarden, The Netherlands. Neuromuscular Disorders, 22(7), 659-668.
Le Rumeur E, Hubert JF & Winder SJ (2012) A new twist to coiled coil. FEBS Letters, 586(17), 2717-2722.
Le Rumeur E, Hubert J-F & Winder SJ (2012) A new twist to coiled coil. FEBS Letters.
Broderick MJF, Bobkov A & Winder SJ (2012) Utrophin ABD binds to F-actin in an open conformation. FEBS Open Bio, 2, 6-11.
Singh SM, Molas JF, Kongari N, Bandi S, Mallela KMG, Armstrong GS & Winder SJ (2012) Thermodynamic stability, unfolding kinetics, and aggregation of the N-terminal actin-binding domains of utrophin and dystrophin. Proteins: Structure, Function and Bioformatics.
Brown SC & Winder SJ (2012) Dystroglycan and dystroglycanopathies: Report of the 187th ENMC Workshop 11-13 November 2011, Naarden, The Netherlands. Neuromuscular Disorders.
Parberry-Clark C, Bury JP, Cross SS & Winder SJ (2011) Loss of dystroglycan function in oesophageal cancer.. Histopathology, 59(2), 180-187.
Winder SJ, Lipscomb L, Angela Parkin C & Juusola M (2011) The proteasomal inhibitor MG132 prevents muscular dystrophy in zebrafish.. PLoS Curr, 3, RRN1286.
Le Rumeur E, Winder SJ & Hubert JF (2010) Dystrophin: More than just the sum of its parts. BBA-PROTEINS PROTEOM, 1804(9), 1713-1722.
Moore CJ & Winder SJ (2010) Dystroglycan versatility in cell adhesion: a tale of multiple motifs.. Cell Commun Signal, 8, 3. View this article in WRRO
Thompson O, Moore CJ, Hussain S-A, Kleino I, Peckham M, Hohenester E, Ayscough KR, Saksela K & Winder SJ (2010) Modulation of cell spreading and cell-substrate adhesion dynamics by dystroglycan.. J Cell Sci, 123(Pt 1), 118-127.
Robertson AS, Allwood EG, Smith APC, Gardiner FC, Costa R, Winder SJ & Ayscough KR (2009) The WASP homologue Las17 activates the novel actin-regulatory activity of Ysc84 to promote endocytosis in yeast.. Mol Biol Cell, 20(6), 1618-1628.
Cross SS, Lippitt J, Mitchell A, Hollingsbury F, Balasubramanian SP, Reed MWR, Eaton C, Catto JW, Hamdy F & Winder SJ (2008) Expression of beta-dystroglycan is reduced or absent in many human carcinomas.. Histopathology, 53(5), 561-566.
Gheorghe DM, Aghamohammadzadeh S, Smaczynska-de Rooij II, Allwood EG, Winder SJ & Ayscough KR (2008) Interactions between the yeast SM22 homologue Scp1 and actin demonstrate the importance of actin bundling in endocytosis.. J Biol Chem, 283(22), 15037-15046.
Bryant RJ, Winder SJ, Cross SS, Hamdy FC & Cunliffe VT (2008) The Polycomb Group protein EZH2 regulates actin polymerization in human prostate cancer cells.. Prostate, 68(3), 255-263.
Thompson O, Kleino I, Crimaldi L, Gimona M, Saksela K & Winder SJ (2008) Dystroglycan, Tks5 and Src mediated assembly of podosomes in myoblasts.. PLoS One, 3(11), e3638. View this article in WRRO
Higginson JR, Thompson O & Winder SJ (2008) Targeting of dystroglycan to the cleavage furrow and midbody in cytokinesis.. Int J Biochem Cell Biol, 40(5), 892-900.
Avizienyte E, Keppler M, Sandilands E, Brunton VG, Winder SJ, Ng T & Frame MC (2007) An active Src kinase-beta-actin association is linked to actin dynamics at the periphery of colon cancer cells. EXP CELL RES, 313(15), 3175-3188.
Anderson C, Winder SJ & Borycki A-G (2007) Dystroglycan protein distribution coincides with basement membranes and muscle differentiation during mouse embryogenesis.. Dev Dyn, 236(9), 2627-2635.
Rezniczek GA, Konieczny P, Nikolic B, Reipert S, Schneller D, Abrahamsberg C, Davies KE, Winder SJ & Wiche G (2007) Plectin 1f scaffolding at the sarcolemma of dystrophic (mdx) muscle fibers through multiple interactions with beta-dystroglycan. J CELL BIOL, 176(7), 965-977. View this article in WRRO
Hnia K, Zouiten D, Cantel S, Chazalette D, Hugon G, Fehrentz JA, Masmoudi A, Diment A, Bramham J, Mornet D & Winder SJ (2007) ZZ domain of dystrophin and utrophin: topology and mapping of a beta-dystroglycan interaction site. BIOCHEM J, 401, 667-677.
Batchelor CL, Higginson JR, Chen Y-J, Vanni C, Eva A & Winder SJ (2007) Recruitment of Dbl by ezrin and dystroglycan drives membrane proximal Cdc42 activation and filopodia formation.. Cell Cycle, 6(3), 353-363.
Lin N, Chen A, Mackley JR, Winder SJ & Yokota H (2007) AntModeler analysis of mechanical stress driven transcription in three cell types. AIP Conference Proceedings, 953, 122-131.
Mackley JR, Ando J, Herzyk P & Winder SJ (2006) Phenotypic responses to mechanical stress in fibroblasts from tendon, cornea and skin.. Biochem J, 396(2), 307-316.
Batchelor CL & Winder SJ (2006) Sparks, signals and shock absorbers: how dystrophin loss causes muscular dystrophy.. Trends Cell Biol, 16(4), 198-205.
Thompson O, Winder S & Peckham M (2006) Dystroglycan in cell motility and adhesion. The FASEB Journal, 20(5), lb3-lb3.
Higginson JR & Winder SJ (2005) Dystroglycan: a multifunctional adaptor protein.. Biochem Soc Trans, 33(Pt 6), 1254-1255.
Winder SJ & Ayscough KR (2005) Actin-binding proteins.. J Cell Sci, 118(Pt 4), 651-654.
Broderick MJF & Winder SJ (2005) Spectrin, alpha-actinin, and dystrophin.. Adv Protein Chem, 70, 203-246.
Winder SJ (2004) Filopodia formation and Disabled degradation downstream of Reelin.. Biochem J, 384(Pt 1), e1-e2.
Ayscough KR & Winder SJ (2004) Two billion years of actin. Meeting on cytoskeletal dynamics: from cell biology to developmental disease.. EMBO Rep, 5(10), 947-952.
Spence HJ, Chen YJ, Batchelor CL, Higginson JR, Suila H, Carpen O & Winder SJ (2004) Ezrin-dependent regulation of the actin cytoskeleton by beta-dystroglycan. HUM MOL GENET, 13(15), 1657-1668.
Spence HJ, Dhillon AS, James M & Winder SJ (2004) Dystroglycan, a scaffold for the ERK-MAP kinase cascade. EMBO REP, 5(5), 484-489.
Gourlay CW, Carpp LN, Timpson P, Winder SJ & Ayscough KR (2004) A role for the actin cytoskeleton in cell death and aging in yeast.. J Cell Biol, 164(6), 803-809. View this article in WRRO
Chen YJ, Spence HJ, Cameron JM, Jess T, Ilsley JL & Winder SJ (2003) Direct interaction of beta-dystroglycan with F-actin. BIOCHEM J, 375, 329-337.
Winder SJ, Jess T & Ayscough KR (2003) SCP1 encodes an actin-bundling protein in yeast.. Biochem J, 375(Pt 2), 287-295.
Winder SJ & Marston G () Are Soy Products Effective in DMD?. PLoS Currents. View this article in WRRO
García‐Aguirre I, Alamillo‐Iniesta A, Rodríguez‐Pérez R, Vélez‐Aguilera G, Amaro‐Encarnación E, Jiménez‐Gutiérrez E, Vásquez‐Limeta A, Samuel Laredo‐Cisneros M, Morales‐Lázaro SL, Tiburcio‐Félix R , Ortega A et al () Enhanced nuclear protein export in premature aging and rescue of the progeria phenotype by modulation of CRM1 activity. Aging Cell. View this article in WRRO

Chapters

Gimona M & Winder SJ () The Calponin Homology (CH) Domain Wiley-VCH Verlag GmbH & Co. KGaA
Gimona M & Winder SJ () The Calponin Homology (CH) Domain, Modular Protein Domains (pp. 321-336). Wiley-VCH Verlag GmbH & Co. KGaA

Conference proceedings papers

Aguilera GV, Lopez JG, Gutierrez EJ, Limeta AV, Cisneros ML, Winder SJ & Cisneros-Vega B (2016) CRM1 mediates nuclear export of beta dystroglycan to maintain correct nuclear envelope integrity and function.. MOLECULAR BIOLOGY OF THE CELL, Vol. 27
Cerecedo DA, Martinez-Vieyra I, Maldonado DG, Hernandez EG & Winder SJ (2015) Association of membrane/lipid rafts with the platelet cytoskeleton and the Caveolin PY14 and its Participation in the Adhesion Process. MOLECULAR BIOLOGY OF THE CELL, Vol. 26
Martinez-Zarate A, Martinez-Vieyra I, Alonso-Rangel L, Cisneros B, Winder SJ & Cerecedo D (2014) Dystroglycan depletion inhibits the functions of differentiated HL-60 cells.. MOLECULAR BIOLOGY OF THE CELL, Vol. 25
Moore C, Mitchell A, La Riviere T, Lipscombe L, Piggott R, Parkin C, Miller G & Winder SJ (2011) Dystroglycan phosphorylation as a therapeutic target for DMD. NEUROMUSCULAR DISORDERS, Vol. 21(9-10) (pp 639-639)
Miller G, Moore C, Lipscomb L, Mitchell A & Winder S (2010) P29 Preventing dystroglycan phosphorylation as a route to therapy in DMD. Neuromuscular Disorders, Vol. 20 (pp S13-S13)
Cross SS, Hollingbury FE, Lippitt JM, Evans CA, Balasubramanian SP, Reed MWR, Handy FC & Winder SJ (2005) Loss of intercellular expression of beta-dystroglycan is a common event in breast cancer. JOURNAL OF PATHOLOGY, Vol. 205 (pp 8-8)
Cross SS, Hollingbury FE, Lippitt JM, Feeley KM, Azzouzi AR, Winder SJ & Hamdy FC (2005) Loss of intercellular expression of beta-dystroglycan is a common event in prostate cancer and is significantly associated with loss of differentiation. JOURNAL OF PATHOLOGY, Vol. 205 (pp 15-15)
Cross SS, Hollingbury FE, Lippitt JM, Catto JW, Hamdy EC & Winder SJ (2005) beta-dystroglycan is constitutively expressed at the intercellular junctions of epithelial cells and this expression is frequently absent in common cancers. JOURNAL OF PATHOLOGY, Vol. 205 (pp 6-6)
Batchelor CL & Winder SJ (2004) ERM-dependent regulation of the actin cytoskeleton by beta-dystroglycan. MOLECULAR BIOLOGY OF THE CELL, Vol. 15 (pp 171A-171A)

Datasets

Winder S Mdx soy diet study wire hanging data.

Teaching activities

Level 1

BMS109 Cell Biology
BMS110 Research Topics in Biomedicine

Level 3

Practical and Dissertation Modules

Level 4/Masters (MSc)

BMS402 Laboratory Research Project (MBiomedSci)
BMS6052 Laboratory Research Project (MSc)

Professional activities and memberships

Member of the Scientific Advisory Board for Duchenne UK
Member of the TREAT NMD Advisory Committee on Therapeutics (TACT)
Member of Editorial Boards of: International Journal of Cell Biology, BioMed Research International, PLoS Currents Muscular Dystrophy, Investigación en Discapacidad, Protein Modules Consortium.
External examiner for Molecular Medicine BSc, School of Biological Sciences, University of Edinburgh, Quinquennial review of MSc in Molecular Medicine, School of Biological Sciences, UEA, External Advisory Board for Biomedical Science, International Islamic University Malaysia, External Advisor to the Board of Studies for Biochemistry, Ramnarain Ruia College, Mumbai,
Recent Invited Conference presentations: 220th ENMC Workshop on ‘Dystroglycan and the dystroglycanopathies’, Naarden, Holland. EMBO Workshop on ‘The modularity of signalling proteins and networks’, Seefeld, Austria. IIUM Zebrafish Workshop, Kuantan, Malaysia. Action Duchenne International Conference, London. 5th International Workshop for Glycosylation Defects in Muscular Dystrophies, Charlotte, NC, USA.
Member of British Society for Cell Biology and Biochemical Society