Research

Small intestinal “mini-gut” organoid generation. Intestinal crypts contain adult stem cells that are responsible for repopulating the gut epithelium during normal day-to-day function and during the healing process following injury. We can grow these crypts in 3D culture to generate “mini-guts” that have all of the features of the epithelium in vivo. Cultures can be maintained for in excess of 1 year allowing many studies to be conducted from a single isolation. We are currently using a “mini-gut” approach to generate novel reliable assays to assess off-target diarrhoeal effects of chemotherapeutic drugs and their mechanisms of action.

What makes the gastrointestinal epithelium tick?

My research interests are focused on the regulation of gastrointestinal architecture and the maintenance of gut homeostasis with a focus on the intestinal epithelium. I am particularly interested in the processes that modulate the susceptibility to the development of drug-induced gastrointestinal toxicity, colitis, colitis-associated cancer and the processes that occur in the gut during the early stages of sepsis. The epithelium consists of a single layer of cells, turning over around once every 5 days, and yet forms a very effective barrier against invasion into the body by bacteria and other microorganisms that are found in great abundance in the intestinal lumen. This barrier function of the intestine fails as either a cause or a consequence of several intestinal and systemic diseases such as inflammatory bowel disease (IBD), coeliac disease (CD), off-target toxic effects of drugs, and sepsis, often resulting in excessive inflammation, epithelial cell destruction and further perpetuation of disease.

My lab aims to target the processes and mechanisms responsible for this breakdown of intestinal barrier function, epithelial cell destruction and inflammation in order to develop novel therapeutic approaches. We have recently identified the NF-κB2 transcription factor as an important regulator of intestinal epithelial damage in murine in vivo models and in intestinal organoid culture, and are currently developing novel methods to modulate the NF-κB2 signalling pathway to prevent injury to the intestinal epithelium.

Organoids - The Conversation with PhD student Louise Thompson

Louise Thompson is a PhD student in the Department of Molecular and Cellular Physiology working with Prof Barry Campbell and Dr Carrie Duckworth. Click here to read Louise's article. Enjoy!The Conversation

Research grants

Intercalating Medical Students MRes

NORTH WEST CANCER RESEARCH INCORPORATING CLATTERBRIDGE CANCER RESEARCH (UK)

September 2019 - September 2021

Research Support Fees for Muhammed Negedu

TERTIARY EDUCATION TRUST FUND (NIGERIA)

December 2019 - November 2023

How does NF kappa B2 signalling contribute to intestinal homeostasis and disease?

ROYAL SOCIETY (CHARITABLE)

November 2017 - October 2018

New tools for investigating enteric host-pathogen interactions in livestock species

BIOTECHNOLOGY & BIOLOGICAL SCIENCE RESEARCH COUNCIL

October 2015 - February 2017

MECNUT: Impact of dietary exposure to emulsifiers on the intestinal mucosa - implications for inflammatory bowel disease and metabolic syndrome

MEDICAL RESEARCH COUNCIL

November 2017 - September 2021

Improved tools for investigating the intestinal uptake and subsequent immune and endocrine responses to novel dietary proteins.

N8 RESEARCH PARTNERSHIP (UK)

July 2017 - September 2018

Targeting intestinal epithelial cell shedding using NF-kB inhibitors to ameliorate sepsis

WELLCOME TRUST (UK)

June 2015 - July 2015

Targeting intestinal epithelial cell shedding using NF-kB inhibitors to ameliorate sepsis

FIONA ELIZABETH AGNEW TRUST (UK)

June 2016 - May 2017

Investigating the importance of nuclear factor kappa B (NF-κB) signalling in the intestinal epithelial cell response to gliadin-derived peptides

THE PHYSIOLOGICAL SOCIETY (UK)

October 2015 - September 2016

The importance of NF-kB regulation in inflammatory bowel disease

EPISTEM LTD (UK)

October 2013 - September 2016

VIP Award- Dr Carrie Duckworth

WELLCOME TRUST (UK)

March 2011 - May 2011