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Celiac disease: from lincRNAs to disease mechanism

Objective

Celiac disease affects at least 1% of the world population. Its onset is triggered by gluten, a common dietary protein, however, its etiology is poorly understood. More than 80% of patients are not properly diagnosed and they therefore do not follow a gluten-free diet, thereby increasing their risk for disease-associated complications and early death. A better understanding of the disease biology would improve the diagnosis, prevention, and treatment of celiac disease.

This project investigates the disease mechanisms in celiac disease by using predisposing genes and genetic variants as disease initiating factors. Specifically, it will investigate if long, intergenic non-coding RNAs (lincRNAs) are causally involved in celiac disease pathogenesis by regulating protein-coding genes and pathways associated with the disease.

This project is based on two important observations by my group: (1) Our genetic studies, which led to identifying 39 celiac disease risk loci, suggest that the mechanism underlying the disease is largely governed by dysregulation of gene expression. (2) We uncovered a previously unrecognized role for lincRNAs that provides clues as to exactly how genetic variation causes disease, as this class of biologically important RNA molecules regulate gene expression.

The research will be performed in CD4+ T cells, a severely affected cell type in disease pathology. I will first use celiac disease-associated protein-coding genes to delineate their regulatory pathways and then study the transcriptional programs of lincRNAs present in celiac disease loci. Next I will combine the information and investigate if the expressed lincRNAs modulate the pathways and affect T cell function, thereby discovering if lincRNAs are a missing link between non-coding genetic variation and protein-coding genes. Our findings may well lead to potential therapeutic targets and provide a solid scientific basis for new diagnostic markers, particularly biomarkers, based on genetics.

Call for proposal

ERC-2012-ADG_20120314
See other projects for this call

Host institution

ACADEMISCH ZIEKENHUIS GRONINGEN
Address
Hanzeplein 1
9713 GZ Groningen
Netherlands
Activity type
Higher or Secondary Education Establishments
EU contribution
€ 2 319 914
Principal investigator
Tjitske Nienke Wijmenga (Prof.)
Administrative Contact
Hubertina H.M. Lauvenberg (Mrs.)

Beneficiaries (1)

ACADEMISCH ZIEKENHUIS GRONINGEN
Netherlands
EU contribution
€ 2 319 914
Address
Hanzeplein 1
9713 GZ Groningen
Activity type
Higher or Secondary Education Establishments
Principal investigator
Tjitske Nienke Wijmenga (Prof.)
Administrative Contact
Hubertina H.M. Lauvenberg (Mrs.)