Research focus
The Kristel Sleegers lab is committed to increase insight in the complex genetics of Alzheimer’s disease and to investigate the translational potential of genetic discovery. We use genetic-epidemiological methods and advanced genomic technologies to identify molecular mechanisms that can serve as future targets for early detection, prevention and treatment.
Techniques include 2 nd and 3 rd generation DNA and RNA sequencing on various biomaterials of a well-characterized locally ascertained study cohort, ranging from targeted through whole exome to whole genome sequencing and in situ sequencing, high-throughput association studies (both common and rare, SNP and CNV) on disease endpoints as well as intermediate and endophenotypes, identification of genetic factors that modify onset age, and polygenic risk profiling. We participate in numerous (inter-) national networks and consortia, to enhance gene identification, interdisciplinary gene characterization and early biomarker discovery.
![](https://uantwerpen.vib.be/assets/public/img/people/color/kristel.png)
Genome-wide association studies (GWAS) have proven to be an excellent tool to locate new AD risk loci, but they are typically not sufficient to detect the actual risk variant(s)
in the locus, let alone their downstream effects.
Identification of alleles directly affecting disease risk, however, is key in understanding the molecular mechanisms through which risk genes are involved in AD. Due to their location in a functional domain, or their mutation mechanism,
these variants may shed light on the mechanism through which a gene is involved in AD, providing anchor points for downstream research. Epidemiological estimates of new risk genes, as well as genetic risk profiling become more precise once these underlying genetic risk variants are known.
Therefore, it is our priority to identify and characterize disease-relevant sequence variants in identified AD risk loci to enhance their translational potential, leveraging the strengths of our local cohort, in terms of its relative homogeneity, rich resources and close connections with clinicians.
My team previously detected a functional CNV in CR1 (Brouwers et al., 2012), rare deleterious variants in CLU leading to reduced CLU secretion (Bettens et al., 2012 & 2015), and rare predicted loss-of-function mutations in SORL1 (Verheijen et al., 2016) as significant risk factors for AD.
In ABCA7 we demonstrated rare predicted loss-of-function mutations that were subject to a natural rescue mechanism through alternative splicing, as well as a pathogenic expansion of a VNTR that strongly increases AD risk (
Cuyvers et al., 2015;
De Roeck et al., 2017 &
2018).
Current projects include an in-depth characterization of ABCA7 genetic variation at transcript level in AD; expression and splicing QTL analysis of novel AD risk loci in the frame of the European Alzheimer Disease Biobank (EADB) consortium GWAS project; whole exome sequencing of AD, MCI and intermediate phenotypes in the frame of the European Medical Information Framework for Alzheimer’s Disease Multimodal Biomarker Discovery study (EMIF-AD MBD); and identification of gene expression signatures of functional connectivity and cognitive decline.
Team
![Kristel Sleegers](https://uantwerpen.vib.be/assets/public/img/staff/user_66_1592565308.png)
Kristel Sleegers
Full Professor UAntwerp, Expert Scientist VIB![Julie van der Zee](https://uantwerpen.vib.be/assets/public/img/staff/user_65_1689252944.png)
Julie van der Zee
Staff Scientist![Fahri Küçükali](https://uantwerpen.vib.be/assets/public/img/staff/user_37_1701794230.png)
Fahri Küçükali
Post-Doctoral Researcher![no picture available](https://uantwerpen.vib.be/assets/public/img/staff/unknown.png)
Jasper Verwilt
Post-Doctoral Researcher![Celeste Laureyssen](https://uantwerpen.vib.be/assets/public/img/staff/user_134_1622308984.png)
Celeste Laureyssen
PhD student![Gonzalo Leguía Fauró](https://uantwerpen.vib.be/assets/public/img/staff/user_138_1644498960.png)
Gonzalo Leguía Fauró
PhD student![no picture available](https://uantwerpen.vib.be/assets/public/img/staff/unknown.png)
Tijs Watzeels
PhD student![Lara De Deyn](https://uantwerpen.vib.be/assets/public/img/staff/user_171_1704894772.png)
Lara De Deyn
Ph.D. Student![no picture available](https://uantwerpen.vib.be/assets/public/img/staff/unknown.png)
Nicole Wawrzyniak
PhD student![no picture available](https://uantwerpen.vib.be/assets/public/img/staff/unknown.png)
Tobi Van den Bossche
PhD student![Jasper Van Dongen](https://uantwerpen.vib.be/assets/public/img/staff/user_81_1611909576.png)
Jasper Van Dongen
Technician