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Receptor Biology Laboratory

Laboratory overview

We investigate tumour growth/spread-promoting proteins in the context of cellular interactions within the tumour microenvironment. As part of the Tumour Targeting Program, our research focuses on cell surface proteins as they are readily accessible for antibodies, which can be developed as new, potentially tumour-selective therapies. We also investigate the function of these proteins in coordinating intercellular interactions that promote tumour development (e.g. by recruiting various tumour growth-aiding cell types to the tumour microenvironment) and which may be targeted by our novel reagents.

We investigate the function of proteins that are upregulated in tumours or their surrounding microenvironment and which we can target with antibodies in order to develop novel potential therapies. A/Prof. Peter Janes, Head, Receptor Biology Laboratory
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Our focus

Eph receptors.

Ephs are receptor tyrosine kinases that bind to cell-bound proteins (ephrins) on adjacent cells and control intercellular adhesion/de-adhesion. Their function in normal cellular development is to coordinate cell movement during formation of tissue boundaries and vascular/neural networks. They are generally scarce in adults but do reappear in cancers, where they are then associated with early ‘progenitor’ cell types, blood vessel formation, and tumour cell invasion and spread. EphA3 is a particular focus in our tumour model investigations and we have developed a specific antibody for testing it in preclinical experiments, as well as part of the broader clinical program.

ADAM metalloproteases.

ADAMs are membrane-bound proteases which cleave and shed a range of other membrane proteins, thereby regulating the activity of diverse cell surface receptors. These include Ephs, EGF/erbB and Notch receptors, all of which are implicated in cancer and together control cell movement, proliferation and differentiation (cell fate). ADAMs also play an important role in the tumour microenvironment and in inflammation. ADAM10 and 17 are of particular interest to us and we are investigating their function, as well as developing antibodies and antibody-drug conjugates as potential therapeutics.

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Quick facts

What’s a cell surface receptor?

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

What’s special about Eph receptors?

Eph receptors are distinctive in that they bind to proteins that are attached to other adjacent cells. They can thereby control cell adhesion, migration and invasion. They are important in normal embryonic development, but reappear in certain cell types present in tumours and their surrounding environment, such as in new tumour blood vessels that support tumour growth and spread.

What’s a protease?

A protease is a protein that 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, but they too become overly active in tumours and their surrounding environment by supporting tumour growth, survival and drug resistance.

  1. Seegar TC, Killingsworth LB, Saha N, Meyer PA, Patra D, Zimmerman B, Janes PW, Rubinstein E, Nikolov DB, Skiniotis G, Kruse AC, Blacklow SC. Structural Basis for Regulated Proteolysis by the α-Secretase ADAM10. Cell, 14; 171(7):1638-1648, 2017.
  2. Atapattu L, Saha N, Chheang C, Eissman MF, Xu K, Vail ME, Hii L, Llerena C,  Liu Z, Horvay K, Abud HE, Kusebauch U, Moritz RL, Ding B-S, Cao Z, Rafii S,  Ernst M, Scott AM, Nikolov DB, Lackmann M and Janes PW.An activated form of ADAM10 is tumor selective and regulates cancer stem-like cells and tumor growth. J Exp Med.  213:1741-57 2016.
  3. Mansour M, Nievergall E, Gegenbauer K, Llerena C, Atapattu L, Hallé M, Tremblay ML, Janes PW*, Lackmann M. 2016.PTP-PEST controls EphA3 activation and ephrin-induced cytoskeletal remodelling.. J Cell Sci. 2016 Jan 15; 129(2):277-89 *Corresponding author.
  4. Vail ME, Murone C, Hii L, Tan A, Abebe D, Janes PW, Lee FT, Baer M, Palath V, Bebbington C, Yarranton G, Llerena C, Garic S, Abramson D, Cartwright G, Scott AM and Lackmann M.Targeting EphA3 inhibits cancer growth by disrupting the tumor stromal microenvironment.. Cancer Res 2014, 74 (16):4470-81.
  5. To C, Farnsworth R, Vail ME, Chheang C, Gargett CE, Murone C, Llerena C, Major AT, Scott AM, Janes PW, and Lackmann M. Hypoxia-controlled EphA3 marks a human endometrium-derived multipotent mesenchymal stromal cell that supports vascular growth.. PLoS One 9:e112106, 2014.

Meet our team

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