Start date

October 2018

Project title                         

Unbiased molecular definition of epithelial barrier defects driving inflammatory bowel disease

supervisorS      

 
Professor Paul Johnson

Professor Alison Simmons

I qualified from Liverpool Medical School in 2012 where I also undertook a MPhil degree in Alder Hey Children’s Hospital characterising the causative agents of Acute Respiratory Infection in pre-school children. This project gave me a basis in immunological principles and basic science techniques and involved collaboration with teams in Liverpool, Brazil, Australia and the USA.

Following this I undertook an NIHR Academic Foundation Year and, alongside clinical training, used the research period to investigate potential novel stem-cell therapies for the treatment of Hirschprung’s disease.

In 2014, I was successfully appointed as a paediatric surgery NIHR Academic Clinical Fellow (ACF) in Oxford. My initial project was with the Transplant Research Immunology Group in the NDS and focused on the potential therapeutic applications of regulatory T cells (Treg) in children with diabetes. During the ACF I also completed a Postgraduate Diploma in Health Research with distinction.

Following this I began working in Professor Simmons laboratory investigating the molecular drivers of inflammation and epithelial barrier breakdown in Inflammatory Bowel Disease - a condition which has an increasing prevalence in paediatric patients and where significant number of patients fail to respond to current medical therapies. For this work I was awarded an Oxford NIHR-BRC clinical research fellowship and a Joint British Association of Paediatric Surgeons-Royal College of Surgeons of England research fellowship. I am now continuing this work as a Wellcome Doctoral (DPhil) training fellowship where I will aim to utilise single cell RNA-sequencing to characterise the drivers of epithelial barrier breakdown in IBD.

My research focuses on the breakdown of the epithelial barrier in Inflammatory Bowel Disease (IBD). IBD, consisting of Ulcerative Colitis and Crohn’s Disease, affects up to 1 in 250 people in the UK and a significant proportion of these are children. Despite best medical therapies up to 40% of patients fail to respond to current treatment. IBD results from a breakdown in immune tolerance to commensal microflora combined with barrier breakdown. The causes of this breakdown is poorly understood at the molecular level.

Using single-cell RNA-sequencing of patient samples I will seek to characterise barrier breakdown in health and IBD in order to identify the pathways which are dysregulated in disease. Following validation of key genes identified, this work will aim to map the molecular drivers of inflammation and identify new targets for IBD therapies and the generation of in vivo models that will more accurately recapitulate human disease.

During this work I will seek to develop these finding into also studying the interaction between the stromal and epithelial compartment of the hindgut during development, with important implications for paediatric surgical patients. In the future apply results to paediatric surgical inflammatory and developmental intestinal diseases which may include Hirschprungs Colitis and Necrotising Enterocolitis.