Paola Scaffidi

Cancer Epigenetics Laboratory

The goal of our laboratory is to uncover fundamental principles of cancer development, with particular emphasis on epigenetic mechanisms regulating cancer stem cell (CSC) function and tumour organisation.

Cancer is a clonal disease originating from a single cell. Yet, most human cancers are characterised by astounding intra-tumour heterogeneity and comprise various subpopulations of cells with distinct phenotypes and biological properties. Even neighbouring cells within a tumour may have different morphologies, express differential transcriptional programs and display specific repertoires of surface molecules. Most importantly, not all cancer cells possess the same proliferative potential and in most cancers only a subset of cells is truly immortal. These cells act as CSCs and are responsible for maintaining the long-term growth of the tumour.

Our group is interested in understanding how epigenetic mechanisms involving histone modifications, higher-order chromatin structure and DNA methylation contribute to intra-tumour heterogeneity and how they affect CSC function.

We use genome-wide mapping approaches and state-of-the-art cell biological methods in combination with advanced light microscopy techniques and in vivo approaches to characterise functionally important epigenetic traits of CSCs, with the ultimate goal of identifying novel therapeutic targets.

Figure 1

Phenotypic intratumour heterogeneity. Immunofluorescence microscopy of a breast cancer section showing highly heterogeneous patterns of methylated histone H3 (green) and histone H1.0 (red). (Click to view larger image)

Selected publications

Morales Torres C; Biran A; Burney MJ;  Patel H; Henser-Brownhill T; Cohen AH; 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, 353, Sept 30, 514-1526.

Fernandez, P; Scaffidi, P; Markert, E; Lee, J-H; Rane, S and Misteli, T. Transformation resistance in a premature aging disorder identifies a tumor-protective function of BRD4. Cell Reports 2014, 9, 248-260

Scaffidi, P and Misteli, T. In vitro generation of human cells with cancer stem cell properties. Nature Cell Biology 2011, 13, 1051-1061 

Scaffidi P, Misteli T. Cancer epigenetics: from disruption of differentiation programs to the emergence of cancer stem cellsCold Spring Harb Symp Quant Biol. 2010;75:251-8

Scaffidi P, Misteli T. Lamin A-dependent misregulation of adult stem cells associated with accelerated ageingNature Cell Biology 2008;10(4):452-9

Scaffidi P, Misteli T. Lamin A-Dependent Nuclear Defects in Human AgeingScience 2006 Apr 27

Scaffidi P, Misteli T. Reversal of the cellular phenotype in the premature aging disease Hutchinson-Gilford progeria syndrome. Nature Medicine 2005 Apr;11(4):440-5. Epub 2005 Mar 6.

Scaffidi P, Misteli T, Bianchi ME. Release of chromatin protein HMGB1 by necrotic cells triggers inflammation. Nature. 2002 Jul 11;418(6894):191-5

Paola Scaffidi

paola.scaffidi@crick.ac.uk
+44 (0)20 379 61325

  • Qualifications and history
  • 2002 PhD, Dibit San Raffaele Scientific Institute, Milan, Italy.
  • 2002 - 2007 Postdoctoral Fellow, Cell Biology of Genomes Group, NCI, NIH, USA
  • 2007 - 2013 Staff Scientist, Cell Biology of Genomes Group, NCI, NIH, USA
  • 2014 Established lab at the London Research Institute, Cancer Research UK
  • 2015 Group Leader, the Francis Crick Institute, London, UK