Marthe Boelens

Sarcomas encompass a diverse group of mesenchymal malignancies with distinct genetic drivers. My research employs Xenopus tropicalis as a genetically tractable model to investigate two subtypes—retroperitoneal liposarcoma (LPS) and desmoid tumors (DT). Using CRISPR/Cas9 gene editing, transcriptomic profiling, and high-resolution 3D imaging, I aim to uncover key molecular mechanisms underlying tumor progression and microenvironment interactions.

Liposarcoma: Investigating Drivers of Dedifferentiation

The two most prevalent subtypes of liposarcoma are well-differentiated (WDLPS) and the more aggressive dedifferentiated form (DDLPS), yet the mechanisms driving dedifferentiation remain unclear. By multiplexing CRISPR/Cas9 to disrupt key tumor suppressor pathways (p53 and Rb), we generated an in vivo Xenopus LPS model exhibiting a mixed WDLPS and DDLPS phenotype. To identify transcriptional programs and regulatory networks driving dedifferentiation, I employ:

• Single-nuclei RNA sequencing to compare the transcriptional profiles of WDLPS and DDLPS with normal fat.

• CRISPR/Cas9-mediated disruption of candidate co-driver genes involved in LPS dedifferentiation.

• Light-sheet microscopy to visualize cellular organization within the distinct tumor regions at high resolution.

This holistic  approach will help pinpoint key factors contributing to the progression of LPS toward its dedifferentiated form.

Desmoid Tumors: Exploring the Tumor Microenvironment

Desmoid tumors (DT) are locally aggressive neoplasms driven by hyperactivated Wnt signaling, a hallmark of immunologically cold cancer types. However, their immune landscape remains poorly characterized. Using a Xenopus model generated through CRISPR/Cas9-mediated apc inactivation, I investigate the immune cell composition and extracellular matrix organization within DT through:

• Single-cell RNA sequencing to profile X. tropicalis immune populations.

• HCR-FISH to spatially map gene expression of immune populations.

• mesoSPIM light-sheet microscopy to generate 3D whole-mount imaging of the tumor and its microenvironment.

This integrative approach aims to uncover potential immune evasion mechanisms, such as immune exclusion and stromal remodeling.
By leveraging Xenopus tropicalis for rapid and scalable genetic engineering, I seek to provide novel insights into sarcoma biology. These findings will contribute to understanding liposarcoma dedifferentiation and the immune landscape of desmoid tumors, with implications for potential therapeutic strategies.
 

• Lab address: Department of Biomedical molecular biology, VIB-UGent, Technologiepark Zwijnaarde 71, 9000 Gent, Belgium
• Providing specific platforms or services for other researchers :
  1) UZ Ghent - Sequencing facility
  2) VIB – X. tropicalis animal facility for preclinical cancer research
• Member of the Consortium for Sarcoma Research Ghent (ConSaRGhent)
• Marthe Boelens is interested to receive invitations for presentations or talks