Cancer Epigenetics
Paola Scaffidi
Group Leader
[email protected] | |
Location |
Building 13
Floor 3rd Via Adamello 16, Milano |
The Cancer Epigenetics laboratory investigates biological processes driven by non-genetic mechanisms, focusing on the role of epigenetic regulators in cancer initiation and maintenance.
Findings over the past 30 years have strongly implicated epigenetic mechanisms in cancer development. We now know that alterations in chromatin and DNA methylation patterns are a universal feature of the disease, that epigenetic regulators are among the most mutated classes of genes across malignancies, and that transcriptional intratumour heterogeneity shapes the organisation of many cancer types. Building on epigenomics, genomics and transcriptomics studies that have comprehensively profiled epigenome-related alterations in patients, a major goal of the laboratory is to uncover the functional impact of epigenetic deregulation in cancer and the molecular mechanisms underlying these effects. To do so, we study how epigenetics cooperate with genetics and cell-to-cell signalling in defining cancer cell behaviour at various stages of the disease.
We combine CRISPR-based approaches to model mutations in epigenetic regulators, genome-wide mapping methods to characterize how the epigenome responds to genetic and environmental challenges, single-cell transcriptomics and in vivo studies to evaluate the biological consequences of these alterations and explore new therapeutic opportunities.
Most Relevant Publications
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Loukas I, Simeoni F, Milan M, Inglese P, Patel H, Goldstone R, East P, Strohbuecker S, Mitter R, Talsania B, Tang W, Ratcliffe CDH, Sahai E, Shahrezaei V, Scaffidi P
Selective advantage of epigenetically disrupted cancer cells via phenotypic inertia.
Cancer Cell, 2023
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Monserrat J, Morales Torres C, Richardson L, Wilson TS, Patel H, Domart MC, Horswell S, Song OR, Jiang M, Crawford M, Bui M, Dalal Y, Scaffidi P
Disruption of the MSL complex inhibits tumour maintenance by exacerbating chromosomal instability.
Nat Cell Biol, 2021
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Chakrabarti AM, Henser-Brownhill T, Monserrat J, Poetsch AR, Luscombe NM, Scaffidi P
Target-Specific Precision of CRISPR-Mediated Genome Editing.
Mol Cell, 2019
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Torres CM, Biran A, Burney MJ, Patel H, Henser-Brownhill T, Cohen AS, Li Y, Ben-Hamo R, Nye E, Spencer-Dene B, Chakravarty P, Efroni S, Matthews N, Misteli T, Meshorer E, Scaffidi P
The linker histone H1.0 generates epigenetic and functional intratumor heterogeneity.
Science, 2016