Dr Stuart McDonald

BSc (Hons), PhD
Senior Lecturer
Group Leader
Twitter
Research Focus

Our research focuses on stem cell niches and clonal expansion in Barrett’s oesophagus, stomach and breast cancer.

Key Publications

Crypt fusion as a homeostatic mechanism in the human colon. In press Gut.

Analysis of clonal expansions through the normal and premalignant human breast epithelium reveals the presence of luminal stem cells. J Pathol (2018) 244(10):61-70. PMID: 28940516

The stem cell organisation, and the proliferative and gene expression profile of Barrett’s epithelium, replicates pyloric-type gastric glands. Gut (2014) 63(12):1854-63. PMID: 24550372

Barrett's metaplasia glands are clonal, contain multiple stem cells and share a common squamous progenitor. Gut (2011) 61(10):1380-9. PMID: 22200839

Major 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
  • Director, The Haemochromatosis Society
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 and location of the 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.

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 around;

  • The cellular origins of Barrett’s oesophagus
  • Field cancerisation of the human stomach
  • Clonal expansion in ductal carcinoma in situ of the human breast
Other Activities
  • Director, The Haemochromatosis Society
  • Member, The Amercian Gastroenterology Association
  • Member, The New York Academy of Sciences
  • Member, The Pathological Society of Great Britain and Ireland
  • Gut, Journal scan review team
  • Reviewer for Gut, J Pathol, Am J Gastroenterol, Stem Cells, Histopathology
  • Reviewer for several funding bodies
Major 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
  • 2014-2017- CORE, Investigating clonal evolution in Barrett’s oesophagus, £210,000
  • 2012- Barts Charity, Clonal expansion and progression of Ductal Carcinoma in situ to cancer in the human breast, £188,333
Recent Publications

Inherited pathogenic mitochondrial DNA mutations and gastrointestinal stem cell populations Su T, Grady JP, Afshar S et al. Journal of Pathology (2018) 246(7) 427-432

Analysis of clonal expansions through the normal and premalignant human breast epithelium reveals the presence of luminal stem cells. Cereser B, Jansen M, Austin E et al. J Pathol (2018) 244(2) 61-70
https://www.ncbi.nlm.nih.gov/pubmed/28940516

Adaptive Clonal Heterogeneity During Oesophageal Cancer Progression Lavery DL, Baker AM, Van der Wel MJ et al. JOURNAL OF PATHOLOGY (2017) 243(1) S11-S11
http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000411734700047&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=612ae0d773dcbdba3046f6df545e9f6a

CLONAL INTERACTIONS AS MECHANISMS OF POLYCLONALITY IN COLORECTAL ADENOMAS Walther V, Davis H, Owusu CK et al. GASTROENTEROLOGY (2017) 152(1) S153-S153
http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000403140300454&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=612ae0d773dcbdba3046f6df545e9f6a

Somatic Evolution of Barrett's/Oesophageal Cancer McDonald SA JOURNAL OF PATHOLOGY (2016) 240(11) 8-8
http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000386691900027&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=612ae0d773dcbdba3046f6df545e9f6a

The complex, clonal, and controversial nature of barrett’s esophagus Evans JA, McDonald SAC Advances in Experimental Medicine and Biology (2016) 908(1) 27-40

OC-012 Do inflammatory polyps show features associated with the early stages of malignant progression? Jawad N, Johnson C, Butterworth E et al. Gut (2015) 64(13) A7.1-A7

Barrett oesophagus: lessons on its origins from the lesion itself. McDonald SAC, Lavery D, Wright NA et al. Nat Rev Gastroenterol Hepatol (2015) 12(2) 50-60
https://www.ncbi.nlm.nih.gov/pubmed/25365976

Opinion : Barrett oesophagus: Lessons on its origins from the lesion itself McDonald SAC, Lavery D, Wright NA et al. Nature Reviews Gastroenterology and Hepatology (2015) 12(7) 50-60

The stem cell organisation, and the proliferative and gene expression profile of Barrett's epithelium, replicates pyloric-type gastric glands. Lavery DL, Nicholson AM, Poulsom R et al. Gut (2014) 63(2) 1854-1863
https://www.ncbi.nlm.nih.gov/pubmed/24550372

For additional publications, please click here
Team

Postdoctoral Researchers in this group
Dr Emanuela CarlottiDr Adam Passman

PhD Students
Ms Viola Walther

Clinical Research Fellows
Dr Richard Hackett

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.