Postdoctoral Fellow – Explore epigenetic mechanisms of anti-cancer drug resistance

Introduction

Are you a cancer biologist fascinated by how tumours escape targeted therapy? Do you want to uncover how epigenetic regulators drive resistance to anti-cancer therapies in lung cancer and test new combination strategies that could help patients with limited options? Then join Oncology R&D at AstraZeneca and unlock the power of what science can do!

About the opportunity

In this Postdoctoral Fellow position, you will investigate how epigenetic mechanisms drive resistance to targeted cancer therapies, and test whether novel combination strategies can overcome it. Your work will focus on lung cancer, where resistance to targeted treatment remains a major unmet need.

You will join the Small Molecule Bioscience team within Oncology Targeted Discovery (OTD) in Cambridge, MA. OTD discovers and develops new targeted medicines for people with cancer, and this project supports AstraZeneca's strategic focus on lung cancer. You will work alongside project teams, epigenetics and data science experts, and an academic mentor, in a collaborative environment where your findings can shape future drug discovery.

Project Focus

This project explores how epigenetic changes allow lung cancer cells to escape targeted therapy. By linking genetically defined cancer models to epigenomic and transcriptomic data, you will uncover the pathways behind resistance, identify potential new targets, and test rational combinations designed to overcome resistance. You will own the project from hypothesis to validation, with the aim of publishing your work. You will be supervised by Lingling Dai, Associate Principal Scientist (Associate Director equivalent) at AstraZeneca, and supported by AstraZeneca experts in lung cancer biology and epigenetics.

What You'll Do

Our Postdoctoral Fellow will lead a three-year research project on the epigenetic basis of resistance to targeted therapy in lung cancer. In a typical week you will run cell-based and in vivo pharmacology experiments, generate and analyse epigenetic sequencing data with colleagues in the Bioscience and Data Science teams, and discuss results with the project team and your academic mentor. You will also prepare data for publication and present your work at internal and external meetings.

Key Duties & Responsibilities

• Investigate how alterations in epigenetic regulators influence sensitivity to targeted therapies, generating engineered cell models (e.g. CRISPR knockout and overexpression).
• Evaluate novel combination strategies to overcome resistance in vitro and in vivo (mouse models).
• Apply epigenomic and transcriptomic profiling (e.g. RNA-seq, ATAC-seq, ChIP-seq or CUT&RUN) to identify the pathways and genes that drive resistance, and validate them using genetic and pharmacological approaches.
• Lead the project in collaboration with the cross-functional AstraZeneca team and our academic collaborators.
• Plan, write, publish and present high-quality scientific papers and conference presentations.

Essential Requirements

• PhD degree in cancer biology, molecular biology or a related field, either awarded within the last 4 years, or due to be awarded within 6 months of joining AstraZeneca
• Strong understanding of cancer biology and mechanisms of resistance to targeted therapy
• Hands-on experience with mammalian cell culture, cell-based assays (e.g. proliferation/viability, western blot, qPCR) and genetic manipulation of cells (e.g. CRISPR knockout, overexpression or knockdown)
• Experience with in vivo mouse tumour models (e.g. xenograft or patient-derived xenograft)
• Experience interpreting complex sequencing datasets to understand biological mechanisms
• Strong publication record, with the ability to plan, analyse and communicate scientific results
• 0-4 years of working experience

Desirable Requirements

• Hands-on experience with epigenomic assays (e.g. ChIP-seq/CUT&RUN, ATAC-seq)
• Knowledge of lung cancer biology