Professor Steve Winder
Professor of Molecular Cell Biology
Director of Postgraduate Teaching
Department of Biomedical Science
The University of Sheffield
Sheffield S10 2TN
Tel: +44 (0) 114 222 2332
Room: B2 06 Florey building
The main research focus of my group is centered around understanding the normal functions of the cell adhesion and signalling adaptor protein dystroglycan and in diseases such as muscular dystrophy and cancer. In particular we are investigating the regulation of the actin cytoskeleton, adhesion mediated signalling and cell motility and invasion using molecular cell biology and transgenic approaches.
My research group is part of the Centre for Membrane Interactions and Dynamics (CMIAD).
Activities and distinctions
Selected publications since 2014
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.