Our research focus

Eph receptors

Eph receptors are cell surface proteins that guide cell migration by binding to other cell-bound proteins (ephrins) on adjacent cells, thereby controlling cell-cell adhesion. Ephs coordinate cell movement during normal development of tissue and organ boundaries, and the vascular and neural networks. They are generally scarce in adults but reappear in cancers, where they are often on early ‘progenitor’ cell types, associated with blood vessel formation, and tumour cell invasion and spread.

EphA3 is a particular focus, which we investigate in tumour models, using ‘knock-down’ mice or by treatment with a specific antibody we helped develop, with the aid of drug payloads to specifically target the tumour microenvironment.

ADAM metalloproteases

ADAM metalloproteases (or ADAMs) are cell membrane-bound proteases that shed a range of other membrane proteins, regulating the activity of diverse cell surface receptors. These include Ephs and other receptors controlling cancer cell growth, drug resistance, and invasion and spread to other tissues. ADAMs also play an important role in the tumour microenvironment and in inflammation.

ADAM10 and 17 are of particular interest and we are investigating their function in tumours, as well as developing antibodies and antibody-drug conjugates as potential new therapies.

Fast facts

Cell surface (or membrane) receptors are proteins attached to a cell’s exterior which can receive external signals, usually by binding with another protein. The bound receptors then send signals into the cell to modify its behaviour, including movement, proliferation and survival.

They are distinctive in that they bind to proteins attached to adjacent cells. This allows them to control cell adhesion, migration and invasion. They are important in normal embryonic development but reappear in certain cell types in tumours and their surrounding environment, including new tumour blood vessels, which support tumour growth and spread.

A protease is a protein which cuts other proteins in a very controlled manner. ADAMs are a type of cell surface metalloprotease (‘metallo’ refers to their dependence on metal ions). ADAM10 and 17 control the activity of various cell surface receptors and are essential in normal cellular development. However they become overly active in tumours and their surrounding environment by supporting tumour growth, survival and drug resistance.

Recent publications

Journal of Experimental Medicine

An activated form of ADAM10 is tumor selective and regulates cancer stem-like cells and tumor growth.
DOI: 10.1084/jem.20151095

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Cancer Research

Targeting EphA3 inhibits cancer growth by disrupting the tumor stromal microenvironment.

DOI: 10.1158/0008-5472.CAN-14-0218

View abstract
Cell

Adam meets Eph: an ADAM substrate recognition module acts as a molecular switch for ephrin cleavage in trans.

DOI: 10.1016/j.cell.2005.08.014

View abstract

Our team

Meet our researchers