Chiara Mozzetta

Associate Professor

chiara.mozzetta@uniroma1.it

Academic Appointments:

  •   2024-to date – Associate Professor, Dept. of Biology and Biotechnology “C. Darwin”. University Sapienza of Rome, (Italy).
  • 2019-2024 Principal Investigator, Tenured Researcher, Institute of Molecular Biology and Pathology (IBPM) – National Research Council (CNR), Rome, (Italy).
  • 2016- 2018 Principal Investigator, Lecturer, Dept. of Biology and Biotechnology “C. Darwin”. University Sapienza of Rome, (Italy).
  • 2013-2016 Senior Post-doc, Institute of Cell Biology and Neurobiology (IBCN), CNR, Rome (Italy). Dr. Lanzuolo lab
  • 2010- 2013 Post-doc at UMR7216 CNRS/University Paris Diderot, Paris (France). Dr. Ait-Si-Ali lab
  • 2009- 2010 Post-doc at IRCCS Fondazione Santa Lucia, Rome, (Italy). Dr. Puri lab
  • 2009- 2009 Visiting Research Scientist at Sanford-Burnham for Medical Research, La Jolla (CA, USA). Dr. Puri lab
  • 2008- 2008 Visiting PhD fellow, University Pierre et Marie, Paris (France). Dr. Sassoon lab
  • 2006- 2007 Visiting PhD student at Sanford-Burnham for Medical Research, La Jolla (CA, USA). Dr. Puri lab
  • 2005- 2009 Post-graduate and PhD fellow, Dulbecco Telethon Institute (DTI), IRCCS Fondazione Santa Lucia and European Brain Research Institute (Italy). Dr. Puri lab

Honors and Awards:

  • 2011-2013 EMBO Long-term post-doc Fellowship
  • 2011-2011 FRM (Fondation pour la Recherche Médicale), short-term post-doc fellowship
  • 2009/2010 Post-doc fellowships granted by AFM (Association Française contre les Myopathies)

Scientific interests

Our laboratory investigates the epigenetic mechanisms governing muscle progenitor cell fate under normal physiological conditions and in pathological states such as muscular dystrophies and rhabdomyosarcomas (RMS). Specifically, we study how chromatin dynamics and nuclear architecture influence cell identity and behavior.

Contribution to Science

We identified Prdm16 as a key regulator of fibro-adipogenic progenitors (FAPs), maintaining their identity by tethering heterochromatin to the nuclear lamina and organizing lamina-associated domains (LADs) (Biferali et al., Sci Adv 2021). We also mapped LADs and H3K9me2-enriched domains (KDDs) in FAPs for the first time.

Following up my previous studies on H3K9 methyltransferases (Mozzetta et al., Mol Cell 2014; Mozzetta et al., Nat Rev Mol Cell Biol, 2015), we discovered that G9a, via the lncRNA Rewind, promotes muscle stem cell proliferation by repressing Wnt7b through H3K9me2 deposition (Cipriano et al., eLife 2021). We also demonstrated that in alveolar rhabdomyosarcoma (RMS), G9a supports tumor survival by partnering with DDX5 to sustain PAX3-FOXO1 expression (Gualtieri et al., Cell Rep 2022); DDX5 also regulates circRNA production in RMS (Dattilo et al., Nat Commun 2023).
Our epigenomic work opens therapeutic avenues in muscle diseases, aligning with the FDA’s recent approval of HDAC inhibitors for DMD—an effort grounded in our earlier preclinical studies (Mozzetta et al., EMBO Mol Med 2013; Saccone et al G&D, 2014; reviewed in Trends Mol Med 2024).

5 Selected publications

  • Mozzetta C, Sartorelli V, Puri PL. HDAC inhibitors as pharmacological treatment for Duchenne muscular dystrophy: a discovery journey from bench to patients. Trends Mol Med. 2024 Feb 25.
  • Bianconi V. and Mozzetta C. Epigenetic control of muscle stem cells: time for a new dimension. Trends in Genetics, 2022 Jan 22.
  • Biferali B., Bianconi V., Fernandez Perez D., Pöhle Kronawitter S., Marullo F., Maggio R., Santini T., Polverino F., Biagioni S., Summa V., Toniatti C., Pasini D., Stricker S., Di Fabio R., Chiacchiera F., Peruzzi G., Mozzetta C. Prdm16-mediated H3K9 methylation controls Fibro-Adipogenic Progenitors identity during skeletal muscle repair.  Science Advances 2021, 7(23), eabd9371
  • Mozzetta C, Boyarchuk E, Pontis J, Ait-Si-Ali S§. Sound of Silence: The properties and functions of repressive lysine methyltransferases. Nature Review Molecular Cell Biology. 2015 Aug;16(8):499-513. § co-corresponding author
  • Mozzetta C , Pontis J, Fritsch L, Robin P, Portoso M, Proux C, Margueron R, Ait-Si-Ali S§ (2014). The Histone H3 Lysine 9 Methyltransferases G9a and GLP Regulate Polycomb Repressive Complex 2-Mediated Gene Silencing. Molecular Cell. Jan 23;53(2):277-89 Epub 2014 Jan 2. § co-corresponding

On-going Grants

Project Title Funding source Amount (Euros) Period Role of the PI
Reprogramming of Genome-Nuclear Lamina Interactions in Fibro-Adipogenic Progenitors During Regeneration and Aging Pasteur-Cenci Bolognetti Anna Tramontano Grant 40.000 2025-2027 PI ( 10% of time)
Aberrant chromatin-nuclear lamina interactions in stromal cells as underlying mechanism of rhabdomyosarcoma initiation Investigator Grant (IG) from the Italian Association for Cancer Research (AIRC) 630.000 2023-2028 PI (20 % of time)
Assessing the role of Fibro-Adipogenic Progenitors in EDMD Muscular Dystrophy Association (MDA) 244.741 2022-2025 PI ( 15% of time)

Complete list of published work in MyBibliography:

https://pubmed.ncbi.nlm.nih.gov/?term=Mozzetta+Chiara&sort=date

 KEYWORDS:

Muscle Stem Cells, Fibro-Adipogenic Progenitors, Skeletal Muscle, Nuclear Lamina, Epigenetics, H3K9 methylation.

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