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.
We investigate 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.
Catalyzing change: Implementing standardised reporting in monogenic inflammatory bowel disease research.
Yeh P-J. et al, (2024), J Pediatr Gastroenterol Nutr
The Human GP130 Cytokine Receptor and Its Expression-an Atlas and Functional Taxonomy of Genetic Variants.
Chen Y-H. et al, (2023), Journal of clinical immunology, 44
Structural and non-coding variants increase the diagnostic yield of clinical whole genome sequencing for rare diseases.
Pagnamenta AT. et al, (2023), Genome medicine, 15
Author Correction: Inflammation across tissues: can shared cell biology help design smarter trials?
Hosack T. et al, (2023), Nature reviews. Rheumatology
Precision medicine in monogenic inflammatory bowel disease: proposed mIBD REPORT standards.
Uhlig HH. et al, (2023), Nature reviews. Gastroenterology & hepatology