Professor of Paediatric Gastroenterology
The gastrointestinal immune system has evolved to counteract the invasion of pathogens. To allow a strong inflammatory immune response during infection but avoid tissue damage there is a need for effective immune regulation. Defects in immune regulation lead to immunopathology such as inflammatory bowel disease or celiac disease.
About one-fifth of all patients with IBD present with initial symptoms during childhood and adolescents. In particular in the very young children patients, an underlying immunodeficiency may cause IBD-like symptoms. The analysis of immune deviation in children with IBD and IBD-like symptoms may contribute to the understanding of the complex puzzle of molecular mechanisms involved in IBD.
To investigate novel genetic defects to lead to very early onset intestinal inflammation we established the COLORS in IBD study (COLitis of early Onset - Rare diseaseS withIN IBD). COLORS in IBD has several international collaborators. In collaboration with the Sanger Center Cambridge and the Wellcome Centre for Human Genetics (WHG) Oxford, we investigate patients with pediatric-onset of IBD using next-generation sequencing.
We investigate several functional mechanisms of intestinal inflammation: antimicrobial activity in phagocytes, regulatory T cells, and epithelial barrier defects.
One key interest of the lab is to understand cytokine responses, in particular, IL-6 and IL-10 family cytokine responses.
A further area of interest is the immune response in patients with defects in the PI3K signaling pathway. One large group of patients with defects in this pathway have mutations in the phosphatase PTEN. Due to heterozygous mutations in the PTEN gene patients develop the PTEN hamartoma tumor syndrome which includes Bannayan Riley Ruvalcaba syndrome and Cowden's syndrome. We investigate the functional consequences of PTEN deficiency for the development of the mucosa-associated lymphoid tissue, B and T cell responses.
Large-scale sequencing identifies multiple genes and rare variants associated with Crohn's disease susceptibility.
Sazonovs A. et al, (2022), Nature genetics
Chromosomal numeric aberrations and rare copy number variation in patients with inflammatory bowel disease.
Dirvanskyte P. et al, (2022), Journal of Crohn's & colitis
Monogenic inflammatory bowel disease-genetic variants, functional mechanisms and personalised medicine in clinical practice.
Azabdaftari A. et al, (2022), Human genetics
Author Correction: Somatic mosaicism and common genetic variation contribute to the risk of very-early-onset inflammatory bowel disease.
Serra EG. et al, (2022), Nature communications, 13
An Integrated Taxonomy for Monogenic Inflammatory Bowel Disease (vol 162, pg 859, 2022)
Bolton C. et al, (2022), GASTROENTEROLOGY, 162, 2143 - 2143