Joshua Robert Goulding
Doctoral fellow - Pediatric Precision Oncology Lab Ghent (PPOL), Center for Medical Genetics (CMGG), Faculty of Medicine and Health Science, UGent
Member of the VAGABOND Consortium (Marie Sklodowska-Curie Actions Innovative Training Network coordinated by the Prinses Máxima Centrum)
Principal investigator: prof. Frank Speleman (PhD)
Neuroblastoma (NB) is a paediatric tumour of the sympathetic nervous system that accounts for 15% of all childhood cancer mortalities.
NB presents with a low mutational burden yet characteristic copy number amplifications, with high-risk NB attributed to the amplification of the MYCN oncogene on chromosome 2. NB tumour cells accumulate DNA damage and a high level of replicative stress, which can distinguish cancer cells from healthy tissue.
Our lab established dependency genes in high-risk NB involved in DNA repair mechanisms and by pharmacologically targeting these characteristics via the ATR kinase axis, we can further increase the replicative stress in the cancer cells and push them to cell death. After extensive in vitro testing of potential therapeutics, toxicity and efficacy must be modelled in vivo to more accurately recapitulate the tumour microenvironment. However, the gold standard of in vivo mouse xenografting is not well suited to compound testing in NB due to the small amount of patient material obtained from thin-needle biopsies and long turn-around time. Zebrafish larvae xenografts have emerged as an attractive alternative for this purpose, with their quick generation time (1 week assay), low amount of patient material required (500-1000 cells per larvae), and relative low-cost amongst other advantages. Additionally, the small size of zebrafish larvae enables high-throughput drug testing in a 96-well plate format. We are developing a zebrafish larvae xenograft platform for high-throughput compound evaluation in NB. After screening compounds for their ability to reduce tumour volume in vivo, we will further characterise their effects with downstream immunohistochemistry, bulk and single-cell RNA sequencing and phospho-proteomics.
This approach is applicable for preclinical drug testing and can be utilised in a personalised medicine platform for NB patients as well as other paediatric cancers.
Born in Liverpool, United Kingdom, I moved to London to complete my integrated masters in Molecular Genetics at King’s College London.
I then gained an interest in paediatric oncology whilst working as a research analyst at the Cancer Center Amsterdam as part of the Hulleman Group, where there is a focus on Diffuse Midline Glioma as well as other high-grade paediatric brain tumours. Here I performed kinome-wide CRISPR screens in primary, patient-derived organoids in combination with clinically approved compounds to uncover synergistic targets and resistance mechanisms utilised by these devastating tumours.
After becoming a member of the VAGABOND Consortium, I am delighted to be pursuing my PhD in the Pediatric Precision Oncology Lab (PPOL) Gent and for the opportunity in CRIG to continue to try and combat these deadly childhood diseases.
Contact & links
- Lab address: Center for Medical Genetics Ghent (CMGG), Medical Research Building 1 (MRB1), 2nd floor, campus UZ Gent, Corneel Heymanslaan 10, entrance 34, 9000 Ghent, Belgium
- Speleman lab
- Center for Medical Genetics Ghent
- Joshua Robert Goulding is interested to receive invitations for presentations or talks