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David Fawkner-Corbett

MBChB MPhil MRCS PgDip DPhil

NIHR Academic Clinical Lecturer in Paediatric Surgery

  • Junior Research Fellow, Wolfson College


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.

After 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 Hirschsprung’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 on from 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 built on these and undertook a Wellcome Doctoral (DPhil) training fellowship which utilised single cell RNA-sequencing (scRNA-seq) to characterise the drivers of epithelial barrier breakdown in IBD - demonstrating previously unappreciated facets of epithelial cell diversity (e.g. BEST4/OTOP2 cell), and novel drivers of barrier breakdown in IBD (e.g. WFDC2) which were reported in Nature.

To help place the hierachy of intestinal cell diversity within human, and understand how the intestine develops from a single tube in embryonal life to the multi-compartmental organ at birth, further work collected rare sample from the Human Developmental Biology Resource to generate a multi-compartment resource of cellular diversity across time revealing the mechanisms underpinning the establishment of crypt-villus axis, stem cell diversity, immune follicle formation and neural colonisation (Cell, 2021).

As an NIHR academic clinical lecturer in paediatric surgery my research focuses on understanding the intestine after birth and through childhood maturity, when it will be the prime site of antigen exposure and immune cell maturation. Using high resolution multi-omic techniques it is aimed to characterise this period from samples collected during intestinal resection (MIMIC study) and provide a roadmap to understand rare developmental disorders of the intestine such as Necrotising Enterocolitis and Hirschsprung's disease.

My Research

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.

I will also hope to study the interaction between the stromal and epithelial compartment with relation to developmental changes. This could generate results that apply to paediatric surgical inflammatory and developmental intestinal diseases such as Hirschsprung's disease and Necrotising Enterocolitis. 

Recent publications

More publications