Francesca Mattiroli will set up her group at the Hubrecht Institute in January 2018, where they will investigate the mechanism of epigenome inheritance, integrating biochemical, structural and cell biology approaches. The Mattiroli group uses recombinant reconstitutions of chromatin duplication reactions and studies the biophysical and structural properties of key protein-protein interactions, to elucidate the mechanisms that control duplication of the epigenetic information during cell division and in situation of DNA damage. These studies will reveal how cells control fate and survival, paving the way to potential new therapeutic strategies in cancer and other diseases.
- Group leader at the Hubrecht Institute from 2018
- Recipient of a Dutch Cancer Society Postdoctoral Fellowship in 2015
- Recipient of an EMBO long-term fellowship in 2014
- Postdoc (2013-2017) in the group of Karolin Luger at the Howard Hughes Medical Institute, at the University of Colorado in Boulder, USA
- PhD (2006-2013; Cum laude) in the group of Titia Sixma at the Netherlands Cancer Institute in Amsterdam, The Netherlands
The Mattiroli group studies chromatin dynamics during DNA replication to understand how the epigenetic information is faithfully propagated during cell division. In eukaryotes, chromatin organizes the genetic and epigenetic information of the cell. The epigenetic information ensures the spatial and timely organization of gene transcription that determines cell identity. Aberrant regulation of the epigenetic information results in changes in cell fate decisions, thereby affecting development and tissue homeostasis, and ultimately leading to disease, such as cancer.
Structure of Histone-based Chromatin in Archaea.
Mattiroli F*, Bhattacharyya S*, Dyer PN, White AE, Sandman K, Burkhart BW, Byrne KR, Lee T, Ahn NG, Santangelo TJ, Reeve JN, Luger K.
Science 2017 Aug 11;357(6351):609-612.
DNA-mediated association of two histone-bound complexes of yeast Chromatin Assembly Factor-1 (CAF-1) drives tetrasome assembly in the wake of DNA replication.
Mattiroli F*, Gu Y*, Yadav T, Balsbaugh JL, Harry MR, Findlay ES, Liu Y, Radebaugh CA, Stargell LA, Ahn NG, Whitehouse I, Luger K.
Elife 2017 Mar;6. doi: 10.7554/eLife.22799.
The Cac2 subunit is essential for productive histone binding and nucleosome assembly in CAF-1.
Mattiroli F*, Gu Y*, Balsbaugh JL, Ahn NG, Luger K.
Sci Rep. 2017 Apr;7:46274.
The nucleosome acidic patch plays a critical role in RNF168-dependent ubiquitination of histone H2A.
Mattiroli F*, Uckelmann M*, Sahtoe DD, van Dijk WJ, Sixma TK.
Nat Commun. 2014;5:3291.
RNF168 ubiquitinates K13-15 on H2A/H2AX to drive DNA damage signaling.
Mattiroli F, Vissers JHA, van Dijk WJ, Ikpa P, Citterio E, Vermeulen W, Marteijn JA, Sixma TK.
Cell (2012), 150(6): 1182-95.
RNF8- and RNF168-dependent degradation of KDM4A/JMJD2A triggers 53BP1 recruitment to DNA damage sites.
Mallette FA, Mattiroli F, Cui G, Young LC, Hendzel MJ, Mer G, Sixma TK, Richard S.
EMBO J. (2012), 31(8):1865-78.