Research field: Adhesion and signaling in development and disease

Group leader: Prof. Dr. Kris Vleminckx

Tel:+32 9 33 13 760  -  Fax:+32 9 221 76 73
E-mail: Kris.Vleminckx.spam.detractor@irc.UGentspam.corruptor.be

(Note: Kris Vleminckx's lab is part of the UGent Department of Biomedical Molecular Biology but not a VIB unit)

Research topic

Our lab uses Xenopus tropicalis, an aquatic vertebrate with externally developing embryos that features a true diploid genome, to model human genetic diseases and cancer. We hereby focus on (rare) Mendelian disorders, retinal degenerative disease and (pediatric) cancer.

CRISPR/Cas9 and TALEN techniques are routinely applied in the lab (with over 80 genes targeted). Because of the size and the external development of their embryos, these techniques are extremely efficient and very simple to apply in Xenopus (as is the case for zebrafish). Due to its diploid genome, Xenopus tropicalis is emerging as an important organism for modeling human genetic disease, very complementary to the zebrafish.

Research Goals : Integrative whole genome and whole exome sequencing analysis is now routinely applied in diagnostic clinical settings. However, in many cases it remains a major challenge for the clinical geneticist to assign causality to specific mutations or aberrations encountered. Hence, versatile animal models are needed to quickly and efficiently test the function for these candidate disease genes. Likewise, advances in DNA sequencing over the past decade have made it possible to systematically analyze the genetic, genomic and epigenetic changes associated with different human cancers. This is exposing novel candidate driver mutations and opening roads for targeted molecular therapies for specific cancer subtypes. Preclinical genetic cancer models are required for rapidly discriminating driver and passenger mutations and identify novel targets for molecular therapy.

Our lab is at the frontline for the use of Xenopus tropicalis as a novel and powerful preclinical model.

Mosaic mutant Xenopus tropicalis injected on its right site with TALENs targeting znrf3 and rnf43 (resulting in duplication of the fore limb) while its left side was injected with a CRISPR guide RNA targeting rspo2 (resulting in the absence of the fore limb) (see Szenker-Ravi et al., Nature 2018).

Photo credit: Amelie Fossul

Area of expertise

• Modelling (rare) human genetic disorders in Xenopus tropicalis
• Generating genetic cancer models using CRISPR/Cas9 multiplexing
• Models for genetic retinal degenerative disease

Technology transfer potential

• Molecular targets in human pathologies, including cancer
• Animal models for compound testing

Selected publications