Professor Steve Winder: Research
Dystroglycan mediated cell adhesion in muscular dystrophy and cancer
Dystroglycan is an essential protein with roles in crucial cellular processes such as cell adhesion, cell motility, cell polarity and cell signalling. It plays a pivotal part in normal cell and developmental processes, but is also a significant player in a number of diseases including muscular dystrophy and cancer.
Background
We are studying the role of dystroglycan both from the perspective of basic cell biology: how it contributes to normal cellular homeostasis, its role in cell adhesion and the cytoskeleton and downstream signalling, and from the perspective of disease, especially where dystroglycan function is altered.
Dystroglycan loss is symptomatic of muscular dystrophies such as Duchenne muscular dystrophy, but also alteration of dystroglycan function through mis-glycosylation underlies a number of other muscular dystrophies collectively known as the dystroglycanopathies, including: Muscle Eye Brain disease, Walker Warburg Syndrome and Congenital Muscular Dystrophy 1C.
Dystroglycan protein is also lost from most adenocarcinomas, but whilst the mechanism of its loss in cancer is different from in muscular dystrophy, understanding the mechanisms and consequences of dystroglycan loss in both disease types is crucial in our efforts to combat these difficult to treat conditions.
Our research
The major focus of our research is in understanding how the transmembrane component of dystroglycan - b-dystroglycan is regulated, and in particular how a key tyrosine residue in the carboxy-terminus of the protein acts as a molecular switch to govern the function and fate of dystroglycan.
Understanding how tyrosine phosphorylation of dystroglycan can not only regulate the 'normal' functions of dystroglycan such as switching between cellular binding partners or targeting it to the nucleus, but also how it can lead to pathological functions such as aberrant cellular targeting or degradation.
We use the full range of molecular and cell biology approaches coupled with fixed and live cell imaging to understand the role of dystroglycan in relevant cellular systems - skeletal muscle cells and prostate cancer cells.
We also use vertebrate models of muscular dystrophy including mice and zebrafish, to further understand the role of dystroglycan in a pathophysiological setting, and also as tools to elucidate new therapeutic strategies.
