Thursday 20th September 2018
Past Research

Gastrointestinal Diseases

DR MARK WILLIAMS

June 2013 – Latest Update for Dr Mark  Williams

It has been a while since I have written. I am pleased to report that our work on human colonic crypts, funded by the Trust, has just been accepted for publication in a very high ranking journal, aptly called Gut (Impact Factor = 10.1).  The manuscript is currently with the publisher for type-setting etc.   I will send you a copy hot off the press.  We have also submitted another paper on human colonic crypts to a journal called Aging Cell and will let you know when we here the outcome.

May 2012 – BARRETT’S OESPHAGUS

A New model To Study Infammatory Signals For Barrett’s Oesphagus

A collaborative research project between the Gastrointestinal Research Laboratory at the University of East Anglia and clinicians at the Norfolk and Norwich University Hospital is developing a new model to study inflammatory signals for Barrett’s Oesophagus. The oesophagus is more commonly known as the food pipe or gullet and is the tube that carries food from your mouth to your stomach. Over the last 30 years oesophageal cancer has become more prevalent and is now the 9th commonest cancer in the UK. There are nearly 8000 new cases diagnosed in the UK each year and the prognosis for this disease is very poor with a mortality rate of 80% (only 10% of sufferers survive for 5 years or more). Risk factors for oesophageal cancer include age, gender (more common in males), smoking, alcohol and a diet low in fruit and vegetables. Also, people with a condition called Barrett’s oesophagus are up to 125 times more likely to develop oesophageal cancer.

Barrett’s oesophagus is thought to develop following long-term acid indigestion (reflux) from the stomach which gives rise to chronic inflammation. In the case of Barrett’s sufferers, the lining of the oesophagus heals itself by replacing the damaged multi-layered lining of the lower oesophagus with a mass of disorganised tubular structures called crypts. It is therefore imperative that the molecular and cellular basis by which inflammatory mediators promote Barrett’s oesophagus and progression to cancer is understood better in order that preventative measures can be deployed following diagnosis at endoscopy. Hitherto, the study of Barrett’s oesophagus has been hampered by the lack of an ex vivo human tissue model of the disease.

Images: A crypt isolated from a Barrett’s oesophagus tissue sample and cultured for three days. The left-hand panel is a bright field image and the right-hand panel is an immunofluorescence image. Proliferative cells are yellow and a responsible for the growth of Barrett’s oesophagus

The Humane Research Trust has funded Miss Natalia Scobioala-Laker in the Gastrointestinal Laboratory to conduct a three year PhD programme of research during which time she has placed human tissue samples of Barrett’s oesophagus into a novel three-dimensional tissue-culture system. Natalia used state-of-the-art fluorescence imaging technologies to identify the inflammatory factors that promote propagation of Barrett’s oesophagus and progression to oesophageal cancer. Work in progress was presented at the prestigious meeting of the American Gastroenterological Association in Chicago (2010). During her study, Natalia demonstrated that similar signals required for the growth of intestinal crypts also drive the growth of Barrett’s crypts.  She is currently writing her thesis and manuscripts for publication.  See below for an update on how Natalia’s PhD studies have transformed her life!

April 2012 – UPDATE : A FAIRY TALE PHD

Decoding cryptic messages that lead to gastrointestinal disease

The lining of the human intestine is the most rapidly renewing tissue in the body and is the site of devastating conditions such as inflammatory bowel disease and colorectal cancer.  Our understanding of these conditions has been hampered by the lack of an ex vivo culture model of the human intestinal epithelium.  Unfortunately, this has placed a greater emphasis on the use of animal models to investigate human intestinal disease.  Over the last few years, however, dramatic progress has been made in establishing culture models of native human intestinal tissue. Significantly, this development permits the comparative study of live, native human tissue derived from healthy individuals with that derived from patients suffering from intestinal diseases.

The Humane Research Trust has provided invaluable support for the development of an ex vivo, 3D culture model of the human intestinal epithelium in the Gastrointestinal Research Laboratory, headed by Dr Mark Williams at the University of East Anglia.  Most recently, Natalia Wharton (nee Scobioala-Laker), a Humane Research Trust PhD student, has developed a 3D culture system for tissue derived from the sufferers of Barrett’s oesophagus; this is a precursor for oesophageal cancer and, just like the lining of the gut, is comprised of flask-like structures called crypts.  Intriguingly, it appears that the cellular signals that maintain intestinal crypts in culture also support the culture of Barrett’s crypts.  These remarkable developments in 3D human tissue culture methodology have been accompanied by the advancement of 4D imaging technology, labelling of stem cells and manipulation of gene expression, which in combination have started to decode the cryptic messages that lead to gastrointestinal disease.

On a personal note, Natalia has not only reached fulfilment from these scientific achievements during her PhD studies, but also in marrying Mr Richard Wharton, a colorectal surgeon, and becoming a mother to their baby boy Aleksandr, a fairy tale PhD!

The Wharton Family

Fluorescent image of a human intestinal crypt, stem cells are red and pink

Establishment of an In Vitro Human Colon ModelUniversity of East Anglia, Norwich

Slide from Dr Mark Williams - Establishment of an in vitro Human Colon Model

Slide from Dr Mark Williams –
Establishment of an in vitro Human Colon Model

This project aims to develop a three-dimensional in vitro culture model of the human intestine. There is a great deal of interest in the prevention of inflammatory bowel diseases and colorectal cancer because they are leading causes of death in the developed world. At present, animal models are in widespread use for studying this subject.

The in vitro model will allow non-animal techniques to be applied to the research, enabling investigation of stem cell proliferation and survival, and progress toward new forms of treatment. The principles involved will also have application to a range of research involving similar tissue elsewhere in the body, such as breast and prostate problems.

Author: glewis