Research
Alterations in a cell’s DNA, both in its sequence and its accessibility, can lead to disease development. Patients bear heterogeneous combinations of genetic and chromatin changes, which drive the diversity of their disease manifestations. The ability to causally link genetic and epigenetic alterations to their consequences on cell states, the plasticity of these states, and disease-relevant phenotypes, will significantly improve our ability to tailor therapies to each patients, based on the specific features of their disease.
Our goal is to understand how the genetic and chromatin state of a cell influence its behaviour during disease development, in particular cancer. We do so by combining single-cell omics technologies (gene expression and chromatin accessibility profiling), computational analyses and molecular biology. Some of our current research themes:
Cancer driver mutations and their impact on cell behaviours and tissue structure in melanoma
We have previously described and characterised novel isogenic human cell models of melanoma that enable causal associations between mutations and their functional consequences (Hodis*, Torlai Triglia* et al., 2022). We are now leveraging these models to study how cancer-driver alterations influence how cells respond to external stimuli and tissue structure.
Impact of mutations in chromatin regulators on tumour development
Genes encoding for chromatin regulators are among the most mutated in cancer. These mutations are hypothesised to provide a plasticity advantage, improving cells’ ability to adapt to challenges like therapy or new environments. We aim to improve our molecular understanding of how these mutations change cell states, and develop strategies to constrain this adaptability.
