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FIELD OF EXPERTISE
- Breast cancer
- Cancer predisposition
- Genome editing
- Zebrafish
- DNA damage response genes
PROJECTS
Background
Germline pathogenic variants in the DNA damage response gene BRCA2 are associated with a significantly increased risk of breast, ovarian, pancreatic, and prostate cancer. Nevertheless, upon diagnostic testing in patients with a presumed genetic predisposition, significant numbers of variants of unknown significance (VUS) are identified in BRCA2. For patients carrying these VUS, clinical data and in vitro functional assays are often insufficient to determine their cancer risk, which is essential to be able to apply risk-reducing interventions, to administer targeted therapies or to offer presymptomatic testing to family members.
Aim
The general aim of this project is setting up in vivo functional assays for the testing of VUS in BRCA2 by developing an efficient CRISPR/Cas9‐based workflow that is capable of knocking-in variants in the zebrafish genome, and subsequently assessing their pathogenicity. This will contribute to accurate classification of VUS in BRCA2 and lead to more adequate genetic counselling and improved clinical and therapeutic management of cancer patients and their relatives.
Strategy
We will compare homology directed repair, base editing, and the recently developed prime editing approach and assess their feasibility for accurately knocking-in VUS in the zebrafish brca2 gene. Moreover, proof-of-concept data will be generated for efficient brca2-VUS causality testing in zebrafish by using an in-house developed toolset of functional read-outs, which we will further expand with promising new assays.
Germline pathogenic variants in the DNA damage response gene BRCA2 are associated with a significantly increased risk of breast, ovarian, pancreatic, and prostate cancer. Nevertheless, upon diagnostic testing in patients with a presumed genetic predisposition, significant numbers of variants of unknown significance (VUS) are identified in BRCA2. For patients carrying these VUS, clinical data and in vitro functional assays are often insufficient to determine their cancer risk, which is essential to be able to apply risk-reducing interventions, to administer targeted therapies or to offer presymptomatic testing to family members.
Aim
The general aim of this project is setting up in vivo functional assays for the testing of VUS in BRCA2 by developing an efficient CRISPR/Cas9‐based workflow that is capable of knocking-in variants in the zebrafish genome, and subsequently assessing their pathogenicity. This will contribute to accurate classification of VUS in BRCA2 and lead to more adequate genetic counselling and improved clinical and therapeutic management of cancer patients and their relatives.
Strategy
We will compare homology directed repair, base editing, and the recently developed prime editing approach and assess their feasibility for accurately knocking-in VUS in the zebrafish brca2 gene. Moreover, proof-of-concept data will be generated for efficient brca2-VUS causality testing in zebrafish by using an in-house developed toolset of functional read-outs, which we will further expand with promising new assays.
DEGREES
- BeSHG Postgraduate course: Permanent Education Course in Human Genetics (Ghent University, 2022)
- Master of Science in Biomedical Sciences (Ghent University, 2021)
- Bachelor of Science in Biomedical Sciences (Ghent University, 2019)