Wijmenga Group – Immunogenetics
Wijmenga’s research group focuses on identifying genetic risk factors associated with immune-mediated diseases. Since 1996 we have found genes that carry risk for celiac disease and shown that this disease shares several genetic factors with other immune-mediated diseases, including Crohn’s disease, rheumatoid arthritis, and type 1 diabetes. We are currently moving beyond gene discovery by translating our findings on predisposing genes into insights on disease mechanisms.
Our work is being directed by two important observations we made. First, we have shown that approximately half of the genetic variants associated with the risk for celiac disease lead to the altered expression of nearby genes (cis-eQTL effect), suggesting that the mechanism underlying celiac disease is largely governed by a dysregulation of gene expression. Second, we have recently discovered that the celiac disease risk SNPs often localize to long non-coding RNAs (lncRNAs). These lncRNAs are a new class of RNA molecule that regulates the levels of expression of protein-coding genes, thereby providing the missing link between non-coding SNP variation and protein-coding genes.
Our current hypothesis is that celiac disease risk variants dysregulate lincRNA expression, leading to a dysregulated transcriptional program that interferes with the normal biological function of the tissues and cell types involved in celiac disease. A Spinoza award (2015) and an ERC advanced grant (2012) allow us to test this hypothesis. In addition, we also focus on the more translational aspects, such as genetic risk profiling and finding biomarkers to identify individuals at-risk of developing celiac disease or other immune-mediated diseases (using the LifeLines-deep cohort).
More generally, we are interested in unraveling the molecular mechanisms involved in a dysregulated immune response. For this, we rely on population biobanks in which we can investigate the immune response under normal and challenged conditions (often using ex vivo immune cells). We use functional genomics to unravel the molecular networks while perturbing the genetic background, or by changing the physiological conditions. We have, for example, studied the effect of stimulating immune cells with Candida albicans and observed an important role for type 1 interferon.
Our work is characterized by an interdisciplinary approach and by the use of large cohorts of both patients and healthy individuals in which we can study specific cell types or look at different levels of molecular information, including the role of the gut microbiome.
Cisca Wijmenga did her PhD research on elucidating the gene for facioscapulohumeral muscular dystrophy. She received two major awards for this work. She then became a postdoc with Francis Collins at the National Human Genome Research Institute at NIH, USA, as a Fogerty fellow.
In 1996 she was appointed an assistant professor at Utrecht University (Netherlands). She focused on the genetics of celiac disease as a model for autoimmune diseases, using a combination of gene expression, genetic association and bioinformatic tools. In 2001 she was awarded a Fulbright scholarship to visit NIH. In 2005 she was awarded an NWO-VICI grant (Netherlands Organization for Scientific Research). In 2007 she moved back to Groningen to become head of the genetics department at the University Medical Center, where she has built up a large and international research section. In 2012 she was elected a member of the Netherlands Royal Academy of Sciences (KNAW) and was awarded an ERC advanced grant to move her research towards functional immunogenetics. In 2015 she received a prestigious Spinoza prize by NWO.
Cisca Wijmenga is regularly invited to speak at or to organize international meetings and symposia. She has trained more than 39 PhD students since 1998, seven of whom gained their PhD cum laude. Her research group is an international team, with people from Spain, Italy, Greece, Poland, Slovenia, Finland, India, China, Russia, Brazil, Mexico and Columbia, as well as the Netherlands. Nearly all her old PhD students have continued their scientific career in the Netherlands or abroad, and received fellowships and awards. More information on Cisca
Her research is funded by:
- Spinoza (NWO)
- Top Institute Food and Nutrition
Publications by C Wijmenga