I have a central role in all research projects focusing on the role of noncoding RNAs. My main aim is to understanding how small and long non-coding RNAs contribute to the pathogenesis of B-cell lymphoma. Ongoing studies include MYC-regulated miRNAs and lncRNAs, as well as miRNA-lncRNA interactions and the role of circular RNAs. We apply state-of-the-art methodology including AGO2-RIP, RNA-FISH and gain- and loss-of-function screens using shRNA and CRISPR-Cas technology.
Latest publications (78) Activities (27) Press/Media (1) Prizes (1) Datasets (2) Supervised work (9)
Proliferation-promoting roles of linear and circular PVT1 are independent of their ability to bind miRNAs in B-cell lymphoma
Published in: International Journal of Biological Macromolecules
Plasmacytoma Variant Translocation 1 (PVT1) is a long non-coding RNA located at 8q24.21 immediately downstream of MYC. Both the linear and circular PVT1 transcripts contribute to cancer pathogenesis by binding microRNAs. However, little is known about their roles in B-cell lymphoma. Here we studied their expression patterns, role in growth, and ability to bind miRNAs in B-cell lymphoma. Linear PVT1 transcripts were downregulated in B-cell cell lymphoma lines compared to germinal center B cells, while circPVT1 levels were increased. Two Hodgkin lymphoma cell lines had a homozygous deletion...
A population-based study of transformed marginal zone lymphoma: identifying outcome-related characteristics
Published in: Blood cancer journal
Histological transformation of marginal zone lymphoma (tMZL) into diffuse large B-cell lymphoma is associated with poor outcomes. Clinical characteristics associated with transformation risk and outcome after transformation are largely unknown due to scarcity of data. In this population-based study, competing risk analyses were performed to elucidate clinical characteristics associated with developing transformation among 1793 MZL patients using the Netherlands Cancer Registry. Cox regression analyses were performed to elucidate clinical characteristics associated with risk of relapse and mortality after transformation. Transformation occurred in 75 (4%) out of 1793 MZL...
CRISPR/Cas9 screen for genome-wide interrogation of essential MYC-bound E-boxes in cancer cells
Published in: Molecular oncology
The transcription factor MYC is a proto-oncogene with a well-documented essential role in the pathogenesis and maintenance of several types of cancer. MYC binds to specific E-box sequences in the genome to regulate gene expression in a cell-type- and developmental-stage-specific manner. To date, a combined analysis of essential MYC-bound E-boxes and their downstream target genes important for growth of different types of cancer is missing. In this study, we designed a CRISPR/Cas9 library to destroy E-box sequences in a genome-wide fashion. In parallel, we used the Brunello library...
Long non-coding RNAs associated with transcriptomic signatures and treatment outcome in diffuse large B-cell lymphoma
Published in: British Journal of Haematology
The lncRNA KTN1-AS1 co-regulates a variety of Myc-target genes and enhances proliferation of Burkitt lymphoma cells
Published in: Human Molecular Genetics
Long noncoding RNAs (lncRNAs) are involved in many normal and oncogenic pathways through a diverse repertoire of transcriptional and posttranscriptional regulatory mechanisms. LncRNAs that are under tight regulation of well-known oncogenic transcription factors such as c-Myc (Myc) are likely to be functionally involved in their disease-promoting mechanisms. Myc is a major driver of many subsets of B cell lymphoma and to date remains an undruggable target. We identified three Myc-induced and four Myc-repressed lncRNAs by use of multiple in vitro models of Myc-driven Burkitt lymphoma and detailed analysis...