Improving cancer therapeutic design through structural biology of ephrin receptors

• PhD and Graduate Research Masters

Ephrin receptors are the largest family of membrane bound receptor tyrosine kinases. Governing how cells interact with their surrounding environment, these critical signaling proteins are implicated in cancer progression. As experts in the non-catalytic activity of pseudokinases, our laboratory is structurally characterising the Ephrin receptors A10 and B6.

This interdisciplinary project will aim to rationally design new tools to accelerate the design of next-generation cancer therapies. In collaboration with the Centre for Biological Therapeutics, we are developing biologics targeting the extracellular domains of Ephrin A10. Concurrently, we aim to identify and develop small molecule inhibitors that target the intracellular pseudokinase domains.

This project will integrate cutting-edge technologies, such as structural biology, chemical biology, proteomics, high-throughput screening and imaging to address critical questions relating to Ephrin pseudokinase signalling dynamics in vitro and in cells.

Our laboratory studies protein kinases, an evolutionarily conserved family of proteins that play a significant role in regulating every aspect of the cell function, including growth, differentiation and cell death. Protein kinases, through their catalytic activity, transfer a phosphate from ATP to a target protein, thus modifying the function of other proteins in the cell. Hence, mutations in protein kinases or their abnormal levels are the underlying cause of many human diseases, including developmental disorders and cancer, making them targets for therapy.

We employ a multidisciplinary approach including kinase biochemistry and biology, structural biology (X-ray crystallography and cryo-electron microscopy), assay development, high-throughput screening, proteomics, imaging and chemical biology to gain high-resolution insights into kinase/pseudokinase signaling proteins.