Current affiliations

• Position

  Reader in Breast Cancer Biology

  Company

  King's College London School of Medicine

  Duration

  2007 - Present

City:

London, England, United Kingdom

Hub:

London

The change to malignancy is associated with changes in the glycans attached to glycolipids and glycoproteins and evidence is now accumulating that this can have a fundamental effect on the tumour cell. The particular form glycosylation of proteins that we are studying is O-linked glycosylation, where glycans are O-linked to serine and/or threonine and the sugars are added individually and sequentially. This type of glycosylation is found on mucin-type molecules or glycoproteins containing mucin-like domains. Our previous work has demonstrated that changes in the expression of glycosyltransferases in breast carcinomas compared to normal breast epithelial can explain, at least in part, the changes in O-linked glycans observed in breast cancers. In particular, two sialyltransferases are upregulated at the RNA level.

We have particularly been studying the membrane mucin known as MUC1, which is upregulated and aberrantly expressed in breast and other carcinomas. The staining of an antibody that specifically recognises MUC1 carrying tumour-associated glycans shows that greater than 90% of breast carcinomas aberrantly glycosylate their O-linked glycans, suggesting that this may elicit some benefit to the tumour.

There are various projects within the laboratory looking at the affect of changes in glycosylation on tumour cells and on the tumour environment.

1. We are investigating the how the O-linked glycosylation of tumour cells affects their migratory ability using normal dendritic cells as a model system.

2. We are investigating the how O-linked glycosylation affects the growth of mammary tumours in a transplantable and a spontaneous model.

3. We are looking at how particular tumour-associated glycoforms of MUC1 interact with immune cells to stimulate an immune response and suppress an immune response. We are also determining if we can exploit the binding of a glycoform of MUC1 to the MGL receptor found on immature dendritic cells to efficiently deliver class I and class II epitopes to dendritic cells.

4. Through an European Grant awarded under FP7 we are investigating the hypothesis that antibodies to aberrantly glycosylated proteins can act as a signature for the diagnosis of breast, pancreatic, ovarian and lung cancer.