Our primary focus is on fusion-driven sarcomas, cancers caused by a single chromosomal rearrangement that fuses two chromatin regulator genes, resulting in a fusion protein that drives tumour growth.
We integrate basic research with preclinical models to explore how these fusion proteins promote cancer and to develop biology-informed therapeutic strategies.
From a fundamental perspective, these cancers, with their genetic simplicity, serve as excellent models for studying gene regulation. On the cancer biology front, their well-defined cancer-driving molecules and straightforward genetics enable us to investigate how these fusion proteins drive tumorigenesis, ultimately advancing the development of better diagnostic tools and treatments.
Investigating Novel Polycomb Associated Proteins
Current Funded Projects:
In previous work, we identified that the oncogenic fusion protein SS18-SSX drives synovial sarcoma by recruiting the activator protein SS18 to genes repressed by the Polycomb repressive complex through the tail of SSX. Polycomb which normally acts as a master regulator of gene silencing for critical developmental genes, is then hijacked by the oncofusion which overrides its silencing and drives instead gene expression of its target genes leading to tumour formation. This Polycomb-linked mechanism is shared by other SSX fusions that drive synovial sarcoma, including EWSR1 and MN1 (Benabdallah et al., 2023).
To determine whether Polycomb dysregulation can explain additional forms of sarcoma, we aim to explore potential associations among several chromatin regulators that have not previously been linked to Polycomb.
A novel therapeutic strategy for bone sarcoma treatment
In this project, funded by the Bone Cancer Research Trust, we are investigating new small molecules to target the Polycomb Repressive Complex 1. Read more about the project here.