Professor Stuart McDonald
Group Leader
Professor of Gastrointestinal Biology
Overview
Our group is investigating the mechanisms of how premalignant diseases such as Barrett's esophagus progress to cancer that has a poor survival rate. Barrett's is common in the UK and all diagnosed patients undergo life-long endoscopic surveillance despite only a small proportion of which (<0.3%) go on to develop cancer each year. There is therefore an unmet clinical need to predict which patients are at high risk of developing cancer. We use phenotypic and omic data to predict outcomes and ask how cellular landscape diversity plays an important role in progression.
Team
Angela Abraham
PhD Student
Dr Yannick Derwa
Clinical Research Fellow
Dr Meng-Lay Lin
Postdoctoral Researcher
Research
Barrett’s oesophagus
Barrett’s is the replacement of the normal squamous oesophageal epithelium with a columnar phenotype and is the major precursor condition of the development of oesophageal adenocarcinoma. All patients with Barrett’s undergo routine and lifelong endoscopic surveillance to detect cancer but the majority of patients never progress to cancer. There are no effective predictive biomarkers for cancer risk and we believe this is because we do not fully understand the evolution to cancer in this condition. My lab has two major CRUK-funded programmes to study different aspects of the progression to cancer. 1) Programme foundation awards to study the diversity of different Barrett’s oesophagus gland types and clonal evolution in the progression to cancer and response to treatment to predict dysplasia risk and therapeutic response. 2) Grand Challenge: To investigate how the stromal reprogramming can prevent and revert inflammation-associated cancers (STORMing Cancer team with Prof Thea Tlsty, University of California San Francisco). Specifically, my lab will study how the stroma changes over time in Barrett’s particularly in patients the progress to cancer.
Stem cells
Epithelial tumours, namely carcinomas, are responsible for >90% of all human malignancies, and intuitively we believe that most, if not all carcinomas, have their origins in normal adult stem cells. Despite a great deal of work in animals, we are still largely ignorant about the nature stem cells in most epithelia. Thus, there is a great need for a robust technique to identify clonogenic cells and their descendants, particularly in human tissues. In particular, how ‘stemness’ can predict future cancer risk is an important question of our lab.
Our laboratory has developed methods to identify clonal proliferative units in human epithelia, and we are now extending these studies to precisely identify the clonogenic cells, their location and nature (multipotential capacity), the cells that are the likely founders of much premalignant disease. We are currently working on the stem cell dynamics of Barrett’s oesophagus using next generation bisulphite sequencing and in the human liver using mitochondrial next generation sequencing, developing molecular clock models to determine stem cell dynamics.
Other interests focus on:
- The role of the microenvironment in the progression of metaplasia to cancer
- The cellular origins of Barrett’s oesophagus
- Field cancerisation of the human stomach
- Hepatocyte stem cell dynamics
Key Publications
Negative selection maintains grossly altered but broadly stable karyotypes in metastatic colorectal cancer. Cancer Discov (2026)16(2):218–233. PMID: 41563072
Concerted changes in Epithelium and Stroma: a multi-scale, multi-omics analysis of progression from Barrett’s Esophagus to adenocarcinoma. Dev Cell (2025)60(20):2807–2824.e7. PMID: 40695287
Alterations of the composition and spatial organization of the microenvironment following non-dysplastic Barrett’s esophagus through progression to cancer. bioRxiv (2025). PMID: 40661356
Hepatocytes undergo punctuated expansion dynamics from a periportal stem cell niche in normal human liver. J Hepatol (2023)79(2):417–432. PMID: 37088309
Clonal transitions and phenotypic evolution in Barrett’s esophagus. Gastroenterology (2022)162(4):1197–1209. PMID: 34973296
Evolutionary dynamics in Barrett oesophagus: implications for surveillance, risk stratification and therapy. Nat Rev Gastroenterol Hepatol (2021)19(2):95–111. PMID: 34728819
See recent publicationsMajor Funding
- 2019- Cancer Research UK, Grand Challenge award, ‘STORMing Cancer: STrOmal ReprograMing provides new directions to prevent and revert chronic inflammation-associated cancers,’ share of £20m
- 2016-2021- Cancer Research UK, Foundation programme award, Investigating the role of gland phenotype in the evolution of Barrett’s oesophagus to dysplasia, ~£1.2m
Other Activities
- UKRI Medical Research Council College of Experts
- CRUK Population and Prevention Committee
- Guts UK Research Board
- Member, Royal Institution
- Member, The New York Academy of Sciences
- Member, The Pathological Society of Great Britain and Ireland
- Member American Association of Cancer Research
- Member, British Society of Gastroenterology
- Member, British, European and International association for Cancer Research
- Member, Biochemical Society
- Gut, Journal scan review team
- Reviewer for Nature, Nature Med, Gastroenterology, Gut, Cancer, Cancer Cell & others.
Biography
After completing my PhD under Prof Tom MacDonald (ICMS), I spent several years researching inflammatory bowel disease and the immunology of infectious diseases of the gut. This eventually led me to work on stem cell biology within the human gastrointestinal tract with Professor Sir Nicholas Wright and Professor Malcolm Alison. I re-joined Barts and the London in November 2008 and have developed my own research interests around the development of premalignant disease into cancer.
Related News
Researchers shed light on the mystery of liver cells’ origins
Understanding how new liver cells are created could inform how and why cell growth spirals out of control in cancer
General News 30 May 2023
Understanding the evolution of Barrett’s oesophagus to cancer
February is Oesophageal Cancer Awareness Month. At Barts Cancer Institute, Queen Mary University of London, a key area of research focus is on a condition that can precede oesophageal cancer called Barrett’s oesophagus.
General News 17 February 2022
Research team awarded £20m funding to tackle cancer’s biggest questions
Dr Stuart McDonald from our Centre for Tumour Biology has been announced by Cancer Research UK as a member of a global research team funded through its Grand Challenge competition- an international funding initiative that aims to answer some of the biggest questions facing cancer research.
General News 23 January 2019