O'NEILL GROUP

 An intro to our lab

 The main research focus in our lab is pancreatic cancer, an unmet clinical need with dismal prognosis.

Members of the group span the whole basic-to-translational research spectrum, with backgrounds in clinical medicine, mathematics, biochemistry, and biomedical sciences. Employing both wet-lab and computational methods, we investigate crucial aspects of (pancreatic) cancer development and therapy. Ongoing projects in the lab broadly cover two key areas:

- Mechanotransduction and signal integration from the extracellular matrix to the nucleus, with a focus on Rassf1a,
- Immuno-oncology and immunotherapy of pancreatic and oesophageal cancers, with a focus on T cells, NK cells, and macrophages.

More recently, we have begun investigating other aspects of cancer, including the complex interplay between cancer and mental health conditions, and the mechanistic modelling of multitargeted therapeutics.

Key Discoveries 

2004                 - Identified the Hippo signalling pathway in humans. Science

2007                 - Reported the first evidence for tumour suppression via Lats1 phosphorylation of YAP.  Mol Cell

2014                 - Demonstrated regulatory control of CDK2 and BRCA2 in response to genomic stress. Nat Cell Biol

2015                 - Identified epigenetic mediated selection of alternative promoters as a mechanism of cell phenotype. Curr Biol

2018-2019   - Outlined a role for Hippo signalling in chromatin regulation at the nuclear envelope. EMBO J, 3 papers

2022                 - Identified TET2 loss/GATA6 silencing as drivers of aggressive PDAC, reversible by metformin & vit C. Gastro

2024                 - Developed human pancreatic avatars as novel disease models. Sci Adv  

2024                 - Described tissue-resident NK cells in the pancreas and their role in tumour control. eLife

2024                 - Developed techniques to explore the tumour microenvironment in mouse models of PDAC. Curr Protoc

2025                 - Demonstrated a role for radiotherapy + immunotherapy therapeutic regimens involving macrophages. Gut 

2025                 - Identified a link between mechanotransduction and neurological diseases. Sci Adv

Industry Links

Oxford BioMedica

Epicombi.ai