Characterization of epigenetic processes regulating the identity and function of T lymphocytes

The research focus of this unit centers on identifying novel epigenetic mechanisms that drive the reprogramming of effector T cells into dysfunctional or exhausted states within the tumor microenvironment. The primary aim is to determine whether T cell exhaustion can be considered a “chromatinopathy,” marked by abnormal chromatin organization and regulation. Specifically, we will investigate how alterations in histone modifications, nuclear architecture, and chromatin topology involved in gene transcription influence the exhausted T cell phenotype. Special attention will be given to the regulation of repressed chromatin, such as heterochromatin, and its role in shaping the anti-tumor response of T cells. The ultimate goal is to leverage these insights to develop novel epigenetic therapies capable of selectively targeting dysfunctional tumor-infiltrating T cells.

Projects

  • Targeted epigenetic approaches to reprogram exhausted T cells into effector T cells.

Team

Nome / NameRuolo / RoleEmail
Giulia SolbiatiPredoctoral Fellowsolbiati@ingm.org

Publications

  • Burattin FV, Vadalà R, Panepuccia M, Ranzani V, Crosti M, Colombo FA, Ruberti C, Erba E, Prati D, Nittoli T, Montini G, Ronchi A, Pugni L, Mosca F, Ricciardi S, Abrignani S, Pietrasanta C, Marasca F*, Bodega B.* LINE1 modulate human T cell function by regulating protein synthesis during the life span. Sci Adv. 2024 Oct 11;10(41)
    *Corresponding author
  • Polimeni B, Marasca F, Ranzani V, Bodega B. IRescue: uncertainty-aware quantification of transposable elements expression at single cell level. Nucleic Acids Res. 2024 Sep 13:
  • Di Gioia V, Zamporlini J, Vadalà R, Parmigiani E, Bodega B, Marasca F. A Versatile Pipeline for Analyzing Dynamic Changes in Nuclear Bodies in a Variety of Cell Types. J Vis Exp. 2024 Jun 28;(208). doi: 10.3791/66874.
  • Tritto V, Bettinaglio P, Mangano E, Cesaretti C, Marasca F, Castronovo C, Bordoni R, Battaglia C, Saletti V, Ranzani V, Bodega B, Eoli M, Natacci F, Riva P. Genetic/epigenetic effects in NF1 microdeletion syndrome: beyond the haploinsufficiency, looking at the contribution of not deleted genes. Hum Genet. 2024 Jun;143(6):775-795.
  • Gasparotto E, Burattin F.V, Di Gioia V, Panepuccia M, Ranzani V, Marasca F and Bodega B. Transposable Elements Co-Option in Genome Evolution and Gene Regulation. Int J Mol Sci. 2023 Feb; 24(3): 2610.
  • Marasca F*, Sinha S*, Vadalà R, Polimeni B, Ranzani V, Paraboschi E.M, Burattin F.V., Ghilotti M., Crosti M., Negri M.L., Campagnoli S., Notarbartolo S., Sartore-Bianchi A, Salvatore Siena S, Prati D, Montini G., Viale G, Torre O, Harari S, Grifantini R, Soldà G, Biffo S, Abrignani A and Bodega B. LINE1 are spliced in non-canonical transcript variants to regulate T cell quiescence and exhaustion. Nat Genet, 2022 Feb;54(2):180-193. * Co-first author
  • Fontana C*, Marasca F*, Provitera L, Mancinelli S, Pesenti N, Sinha S, Passera S, Abrignani S, Mosca F, Lodato S, Bodega B, Fumagalli M. Early Intervention in preterm infants modulates LINE-1 promoter methylation and neurodevelopment. BMC Med. 2021 Feb 5;19(1):42. doi: 10.1186/s12916-020-01896-0.
    * Co-first author
  • Spreafico M, Cafora M, Bragato C, Capitanio D, Marasca F, Bodega B, Mora M, Gelfi C, Marozzi A, Pistocchi A. Targeting HDAC8 to ameliorate skeletal muscle differentiation in Duchenne muscular dystrophy. Pharmacol Res. 2021 Aug;170:105750. doi: 10.1016/j.phrs.2021.105750. Epub 2021 Jun 30. PMID: 34214631
  • Marasca F, Cortesi A, Bodega B 3D COMBO chrRNA-DNA-Immuno FISH. Methods Mol Biol. 2021;2157:281-297. doi: 10.1007/978-1-0716-0664-3_16.
  • Marasca F, Gasparotto E, Polimeni B, Vadalà R, Ranzani V, Bodega B. The sophisticated transcriptional response governed by Transposable Elements in human health and disease. Int J Mol Sci. 2020 30;21(9):3201
  • Marasca F, Cortesi A, Manganaro L, Bodega B. 3D multicolor DNA FISH tool to study nuclear architecture in human primary cells. J Vis Exp. 2020 Jan 25;(155). doi: 10.3791/60712.
  • Cortesi A, Pesant M, Sinha S, Marasca F, Sala E, Gregoretti F, Antonelli L, Oliva G, Chiereghin C, Soldà G, Bodega B. 4q-D4Z4 chromatin architecture regulates the transcription of muscle atrophic genes in facioscapulohumeral muscular dystrophy. Genome Research. 2019 Jun;29(6):883-895. doi: 10.1101/gr.233288.117. Epub 2019 May 16.
  • Mazzola M, Deflorian G, Pezzotta A, Ferrari L, Fazio G, Bresciani E, Saitta C, Ferrari L, Fumagalli M, Parma M, Marasca F, Bodega B, Riva P, Cotelli F, Biondi A, Marozzi A, Cazzaniga G, Pistocchi A. NIPBL: a new player in myeloid cells differentiation. Haematologica. 2019 Jan 10. pii: haematol.2018.200899. doi: 10.3324/haematol.2018.200899.
  • Marasca F, Bodega B, Orlando V. How Polycomb-mediated cell memory deals with a changing environment. Bioessays. 2018 Apr;40 (4):e1700137. doi: 10.1002/bies.201700137. Epub 2018 Mar 9.
  • Bodega B*, Marasca F*, Ranzani V, Cherubini A, Della Valle F, Neguembor MV, Wassef M, Zippo A, Lanzuolo C, Pagani M, Orlando V. A cytosolic Ezh1 isoform modulates a PRC2-Ezh1 epigenetic adaptive response in postmitotic cells. Nature Struct Mol Biol. 2017 May;24(5):444-452.
    * Co-first author
  • Marasca F, Marullo F, Lanzuolo C. Determination of Polycomb Group of Protein Compartmentalization Through Chromatin Fractionation Procedure. Methods Mol Biol. 2016;1480:167-80.

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