Identifying biomarkers of response to the pan-HER/c-ErbB tyrosine kinase inhibitor neratinib

A PhD studentship is available to a highly motivated candidate who wishes to pursue research in identifying biomarkers of response to the pan-HER/c-ErbB tyrosine kinase inhibitor (TKI) neratinib. This project is funded through an SFI Strategic Partnership Programme and will be based at the National Institute for Cellular Biotechnology (NICB), DCU.

Project Description

Neratinib irreversibly inhibits the three kinase-active HER-family members, EGFR, HER2 and HER4 at low nanomolar concentrations. There is evidence that activating mutations in these proteins may act as biomarkers of neratinib response in vitro and in the clinic. HER4 is the least studied of the HER family in this context but in fact has a high frequency of point mutations in clinical datasets across a range of cancer types. While the presence of a mutation does not infer a role in oncogenesis, the high frequency of HER4 mutations in melanoma and gastro-oesophageal cancers, combined with a nanomolar Kd IC50 value of neratinib for HER4, warrants investigation. The candidate will utilise PCR site directed mutagenesis and CRISPR/Cas9 technology to functionally interrogate the impact of clinically relevant HER4 mutations and the impact of HER4 mutations on response to neratinib in vitro.

The ultimate aim of this project is to investigate if HER4 mutations could be used as predictors of response to neratinib and potentially be legitimate therapeutic targets in their own right.

Candidates will be supervised by Prof John Crown (Saint Vincent’s University Hospital/DCU) and Dr Denis Collins (DCU). The project will be based in the Collins research group, Cancer Biotherapeutics, at the NICB, DCU that has local, national and international research and clinical collaborators.

For more information about this project, please contact Dr Denis Collins: [Email Address Removed]

We are seeking highly motivated candidates with a minimum 2.1H (or equivalent), BSc or MSc in Biochemistry, Cell Biology, Molecular Biology or related fields.

Closing Date for Applications: 12th August 2020
Starting Date for PhD: 1st October 2020

To apply, candidates should submit a detailed CV, a personal statement that outlines research interests, past experience and motivation to complete a PhD (2 pages maximum), and contact information for two academic referees by email to: [Email Address Removed]

Unfortunately, we are unable to provide individual feedback to applicants.
Shortlisted candidates will be invited for interview (online).

For more information on the NICB and the Cancer Biotherapeutics group see: https://nicb.ie/portfolio-view/cancer-biotherapeutics/