Submitted by Catherine Atkins on Wed, 08/07/2026 - 15:50
We are delighted to announce that Early Cancer Institute Researchers Professor Rebecca Fitzgerald and Dr John Lizhe Zhuang have been awarded a seven-year Wellcome Discovery Award, in collaboration with the MRC Biostatistics Unit, the CRUK Cambridge Institute and the Stem Cell Institute, together with USA based colleagues from Stanford University and Icahn School of Medicine at Mount Sinai. This highly competitive Discovery Award is designed to support established researchers to pursue bold, transformative research aims, which lead to significant shifts in our understanding and the development of new methodologies that have the potential to improve human life, health, and wellbeing.
The project Professor Fitzgerald, Dr Zhuang and the team will work on is entitled “Understanding the heterogeneity and evolutionary dynamics of Barrett’s oesophagus to predict cancer risk”
Most cancers develop slowly over many years. This time window creates opportunities to detect disease earlier or even prevent it. Yet many are still diagnosed too late for the best possible outcomes. This Wellcome Discovery Award will enable the research team to investigate the earliest stages of oesophageal cancer by studying the precancerous lesion, Barrett's oesophagus, a common condition that increases cancer risk.
Recent work from the group has established Barrett’s oesophagus as an obligate precursor to oesophageal cancer (Nowicki-Osuch & Zhuang, 2021, Science; Zamani & Wu, 2026, Nature Medicine). However, Barrett’s oesophagus is currently managed using a largely “one-size-fits-all” surveillance approach, with clinical decisions often based primarily on the findings from the most recent endoscopy (Fitzgerald, 2026, New England Journal of Medicine).
This programme draws on the group’s unique longitudinal surveillance cohorts, collected over the past three decades, alongside an extensive collection of patient-derived organoid models representing the full disease spectrum, from normal tissue to early cancer.
By uncovering which cells initiate cancer, when key genetic changes occur, and how abnormal cells evade the body's immune defences, the project team aim to build the most comprehensive picture yet of how oesophageal cancer develops. They will then combine these discoveries with clinical information to create a powerful new model that predicts an individual's risk of developing cancer over time.
This research could fundamentally change how Barrett's oesophagus is managed. More accurate prediction of cancer risk would allow patients at highest risk to receive earlier treatment, while sparing those at low risk from unnecessary procedures and anxiety. Beyond oesophageal cancer, the approaches and insights developed through this project could provide a blueprint for understanding the earliest stages of many other cancers, opening new opportunities for prevention, early detection, and more personalised care.
Assistant Research Professor John Lizhe Zhuang, Programme Co-Lead, said:
" This project brings together rich longitudinal clinical data, advanced molecular and spatial profiling, imaging and functional patient-derived organoid models in a way that has not previously been possible. By integrating these approaches, we aim to build a biologically grounded framework that connects molecular, cellular and functional features with patients’ observed trajectories of cancer progression, establishing quantitative benchmarks for future risk assessment. This could help ensure that patients receive the right care at the right time, while avoiding unnecessary tests and treatments for those at lower risk”
Professor Rebecca Fitzgerald, Programme Lead, said:
“We know that cancer does not develop overnight, yet we still understand surprisingly little about the changes that occur in the years before it becomes clinically apparent. Barrett’s oesophagus offers a unique opportunity to study these early steps. By combining a comprehensive collection of patient samples with the latest technologies, we aim to understand why some people progress to cancer while others do not. Ultimately, our ambition is to move Barrett’s surveillance from snapshots of disease to personalised trajectories of cancer risk, delivering individualised risk-assessment tools to guide clinical decision-making.”
References:
- Nowicki-Osuch, K. & Zhuang, L. et al. Molecular phenotyping reveals the identity of Barrett’s esophagus and its malignant transition. Science. 373, 760–767 (2021).
- Zamani, S. A. & Wu, L. et al. Integrated epidemiological and molecular data inform the relationship between precancer and cancer states of esophageal adenocarcinoma. Nat. Med. 32, 1805–1816 (2026).
- Fitzgerald, R. C. Barrett’s Esophagus. New England Journal of Medicine 394, 1723–1735 (2026).