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Holm Uhlig
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.
Recent publications
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Cessation of exclusive breastfeeding and seasonality, but not small intestinal bacterial overgrowth, are associated with environmental enteric dysfunction: A birth cohort study amongst infants in rural Kenya.
Journal article
Crane RJ. et al, (2022), EClinicalMedicine, 47
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UNC45A deficiency causes microvillus inclusion disease-like phenotype by impairing myosin VB-dependent apical trafficking.
Journal article
Duclaux-Loras R. et al, (2022), The Journal of clinical investigation, 132
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Valosin-containing protein-regulated endoplasmic reticulum stress causes NOD2-dependent inflammatory responses.
Journal article
Ghalandary M. et al, (2022), Scientific reports, 12
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Author Correction: Gain-of-function variants in SYK cause immune dysregulation and systemic inflammation in humans and mice
Journal article
Wang L. et al, (2022), Nature Genetics, 54, 213 - 213
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An integrated taxonomy for monogenic inflammatory bowel disease.
Journal article
Bolton C. et al, (2021), Gastroenterology