The tube connecting the throat with the stomach is called the gullet. Cancer of the gullet does not just appear. Years before cancer appears, the mucous membrane of the gullet changes form. This new mucous membrane is called ‘metaplasia’. We do not yet understand where metaplasia comes from. The gullet has glands where metaplasia might come from. In this project, I will make the first-ever 2D model of these glands of the gullet. By understanding where metaplasia of the gullet comes from we can eventually learn how to prevent metaplasia and cancer of the gullet.

Crohns disease, a chronic bowel disorder, frequently necessitates surgery, with post-operative recurrence posing a significant challenge. To address this issue, I explore the potential of microbial DNA present in the bloodstream as a predictive marker for recurrence. Recent discoveries challenging the conventional belief in sterile blood underpin this pioneering research. If successful, it could enhance disease management by enabling early intervention in high-risk patients, while also broadening our understanding of microbial material translocation. Insights from this research may extend to ecological microbiology, environmental science, and other fields, shedding light on the movement of microbes within different ecosystems, beyond healthcare applications.

Barrett’s oesophagus is the precursor oesophageal adenocarcinoma. This disease, which has shown a marked increase in incidence and mortality over the last decades, is often diagnosed at the palliative stage and has a poor prognosis, even at the potentially curative stage. Currently, the two biggest conceptual challenges faced in the field are firstly the molecular basis of Barrett’s oesophagus and secondly its cell of origin. Both aspects we address in the current research. Barrett’s oesophagus in gastrointestinal reflux patients constitutes a columnar epithelium with distal characteristics, prone to progress to oesophageal adenocarcinoma. HOX genes are known mediators of position-dependent morphology. Here we show HOX collinearity in the adult gut and HOXA13 dysregulation of collinearity in both stem cells and their progeny in Barrett’s oesophagus. HOXA13 overexpression appears sufficient to explain both the phenotype (through downregulation of the downregulates the epidermal differentiation complex) and the oncogenic potential of Barrett’s oesophagus. Intriguingly, employing a mouse model that contains a reporter coupled to the HOXA13 promotor we identify a patch in the physiological gastro-oesophageal junction that is characterized by high HOXA13 expression and we observe that HOXA13 expression confers a competitive advantage to cells following epithelial injury by acid and bile. We thus propose that Barrett’s oesophagus and associated oesophageal adenocarcinoma is the consequence of expansion of this gastro-oesophageal HOXA13-expressing compartment following epithelial injury and the visit of Dr Parikh should help us successfully addressing this issue. Dr Parikh has very recently established protocols for single cell measurements of epithelial diversity ((Parikh K, Antanaviciute A, Fawkner-Corbett D, Jagielowicz M, Aulicino A, Lagerholm C, Davis S,Kinchen J, Chen HH, Alham NK, Ashley N, Johnson E, Hublitz P, Bao L, Lukomska J, Andev RS, Björklund E, Kessler BM, Fischer R, Goldin R, Koohy H, Simmons A. (2019) Colonic epithelial cell diversity in health and inflammatory bowel disease. Nature. 2019 Mar;567(7746):49-55) and the present visit should allow us to exploit this technology for our research. More specifically, the specific contributions of each oesophageal epithelial-cell subtype to this process are unknown. Here we hope profile single epithelial cells from HOXA13-transduced cells and controls. We hope to identify previously unknown cellular subtypes, including gradients of progenitor cells, absorptive-like enterocytes and goblet cells within the crypt-like structures