Funded PhD: Understanding the role of HDAC6 to overcome resistance in non-small cell lung cancer

This project aims to decipher exactly how HDAC6 drives resistance and in so doing create effective combination regimens for patients with KRAS-driven NSCLC.

Lung cancer is the leading cause of cancer related deaths worldwide, killing more patients than breast and colorectal combined.

NSCLC accounts for nearly 85% of all cases, with adenocarcinoma (LUAD) being the most common subtype. Approximately 30% of LUAD patients harbour KRAS mutations, historically considered 'undruggable'. However, advances in drug discovery and a deeper understanding of KRAS biology led to the approval of the first targeted KRAS inhibitors in 2021, followed by several others since.

While these developments represent a major breakthrough, resistance to KRAS inhibition has rapidly emerged as a formidable challenge. Clinical studies have identified diverse resistance mechanisms, including; genetic alterations, KRAS amplifications, reactivation of MAPK and PI3K-AKT signalling, MYC amplifications, receptor tyrosine kinase (RTK) mutations, and epithelial-mesenchymal transition (EMT). This complexity highlights the necessity of combinational therapeutic approaches tailored to distinct patient subgroups.

Dr Dowling’s lab have established a unique panel of KRAS inhibitor resistant NSCLC cell lines. Using these cell lines, Dr Dowling’s lab have discovered that histone deacetylase 6 (HDAC6) plays a key role in driving KRAS resistance.

The aim of this project is to create novel combination strategies for the treatment of KRAS resistant NSCLC.

Objectives

  • Characterise KRAS resistance cell lines across specific genotypes of NSCLC.
  • Decipher the role of HDAC6 in driving KRAS resistance.
  • Examine the effect of novel combination regimen for the treatment of KRAS resistant NSCLC. "

This project is funded by a Research Ireland Programme Grant to Precision Oncology Ireland.

Tenure: Four years

Start date: 12 January 2026

Specification

Essential

  •  First class honours degree (1:1) or equivalent in a relevant subject.

Desirable

  • Master's degree in a relevant subject
  • Wet-lab experience
  • Bioinformatics analysis

Application process

Applications must include:

To apply, please access the following link and complete the application form in full.

Apply now

Application deadline: 17 November 2025

Interviews: 8 December 2025

Please note:

  • It is the candidate’s responsibility to ensure the application form is completed in full and on time – late and/or incomplete applications will not normally be assessed.
  • Unfortunately, we are unable to provide individual feedback to applicants.
  • Shortlisted candidates will be invited for interview.
  • At this stage only successful candidates will be contacted to submit, CV, transcripts and other relevant documentation.
  • Only their referees will also be contacted at this stage for a reference.