Translational control of gene expression in normal human cells and in pathological conditions
We are interested in the study of posttranscriptional regulation of gene expression. It is currently estimated that translation controls a large portion of gene expression by restricting protein synthesis to specific mRNAs. We have isolated eIF6, an initiation factor that regulates metabolism at the level of translation, and it is rate-limiting for cellular growth. Multidisciplinary projects address the role of eIF6 in development and disease, and its activity in Shwachman Diamond Syndrome.
The study of translation is extended to human cells from the immune system and from several neoplastic diseases, including multiple myeloma and malignant mesothelioma. By combining cell biology, biochemistry and molecular biology, we aim at the definition of mechanistic steps of translational control that drive pathological phenomena and can become a therapeutic target.
Projects
- Development of new models to study translation in human cancer cells and in the human immune system.
- Definition of therapeutic targets in Shwachman Diamond Syndrome
- Translational control of lipid metabolism
Team
| Nome / Name | Ruolo / Role | |
|---|---|---|
| Elisa Arsuffi | Fellow | arsuffi@ingm.org |
| Giacomo D'andrea | PhD Student | dandrea@ingm.org |
| Nicola Manfrini | Associate Professor | manfrini@ingm.org |
| Annarita Miluzio | Laboratory Technician | miluzio@ingm.org |
| Sara Ricciardi | Associate Professor | ricciardi@ingm.org |
| Kashefi Behrad | Student | kashefi@ingm.org |
| Vanja Tadic | Post Doc | tadic@ingm.org |
| Sidra Ashgar | Post Doc | ashgar@ingm.org |
Publications
- eIF6 links histone acetylation with translational control of HDAC in skeletal muscle.
Scagliola A, Miluzio A, Ferrari I, Brina D, Ricciardi S, Biffo S.
Mol Cell Biochem. 2026;481:3933-3943. - CancerHubs Data Explorer: a web application for investigating mutation-enriched protein interaction hubs in human cancers.
Ferrari I, Arsuffi E, Biffo S, Manfrini N.
BioData Min. 2026;19. - The many ways to inhibit translation by Sorafenib in liver cancer cells.
Contreras L, Ricciardi S, Biffo S, Muntane J, de la Cruz J.
Mol Cell Biochem. 2026;481:245-262. - KDM6A loss enhances oxidative phosphorylation uncovering tissue-level convergent evolution.
Cartalemi AA, Rosano D, Ferrari C, Crupi G, Cassina L, Gatti G, Corigliano F, Punzi S, Villanti I, Dupere-Richer D, et al.
EMBO J. 2026. doi: 10.1038/s44318-026-00891-0. - Translon: a single term for translated regions.
Swirski MI, Tierney JAS, Alba MM, Andreev DE, Aspden JL, Atkins JF, Bassani-Sternberg M, Berry MJ, Biffo S, Boris-Lawrie K, et al.
Nat Methods. 2025;22:2002-2006. doi: 10.1038/s41592-025-02810-3. - Prime editing links the split integrated stress response to pathogenic eIF2B mutations and white matter degeneration.
Scagliola A, Miluzio A, Pauselli M, Ceci M, Biffo S, Ricciardi S.
Cell Death Dis. 2025;17:141. doi: 10.1038/s41419-025-08399-x. - The power of microRNA regulation-insights into immunity and metabolism.
Oliveto S, Manfrini N, Biffo S.
FEBS Lett. 2025;599:1821-1851. doi: 10.1002/1873-3468.70039. - Recycling of ribosomes at stop codons drives the rate of translation and the transition from proliferation to RESt.
Miluzio A, Scagliola A, Ferrari I, Yilmaz H, D’Andrea G, Cassina L, Oliveto S, Ricciardi S, Boletta A, Biffo S.
Mol Cell. 2025;85:4410-4425. doi: 10.1016/j.molcel.2025.11.002. - FAM46C Expression Sensitizes Multiple Myeloma Cells to PF-543-Induced Cytotoxicity.
Miluzio A, De Grossi F, Mancino M, Biffo S, Manfrini N.
Biomolecules. 2025;15. doi: 10.3390/biom15050623. - Coupling mechanisms coordinating mRNA translation with stages of the mRNA lifecycle.
Fama V, Coscujuela Tarrero L, Albanese R, Calviello L, Biffo S, Pelizzola M, Furlan M.
RNA Biol. 2025;22:1-12. doi: 10.1080/15476286.2025.2483001. - A millifluidic bioreactor allows the long term culture of primary lymphocytes or CD34(+) hematopoietic cells while allowing the detection of tumorigenic expansion.
Ritter P, Oliveto S, Cordiglieri C, Fasciani A, Di Buduo CA, Della Volpe L, Bocconi A, Conci C, Miguel CP, Di Micco R, et al.
Front Bioeng Biotechnol. 2024;12:1388312. doi: 10.3389/fbioe.2024.1388312. - The Impact of 3D Nichoids and Matrix Stiffness on Primary Malignant Mesothelioma Cells.
Oliveto S, Ritter P, Deroma G, Miluzio A, Cordiglieri C, Benvenuti MR, Mutti L, Raimondi MT, Biffo S.
Genes (Basel). 2024;15. doi: 10.3390/genes15020199. - CancerHubs: a systematic data mining and elaboration approach for identifying novel cancer-related protein interaction hubs.
Ferrari I, De Grossi F, Lai G, Oliveto S, Deroma G, Biffo S, Manfrini N.
Brief Bioinform. 2024;26. doi: 10.1093/bib/bbae635. - The Paradox of Ribosomal Insufficiency Coupled with Increased Cancer: Shifting the Perspective from the Cancer Cell to the Microenvironment.
D’Andrea G, Deroma G, Miluzio A, Biffo S.
Cancers (Basel). 2024;16. doi: 10.3390/cancers16132392. - Nanodynamo quantifies subcellular RNA dynamics revealing extensive coupling between steps of the RNA life cycle.
Coscujuela Tarrero L, Fama V, D’Andrea G, Maestri S, de Polo A, Biffo S, Furlan M, Pelizzola M.
Nat Commun. 2024;15:7725. doi: 10.1038/s41467-024-51917-2. - The crosstalk between metabolism and translation.
Biffo S, Ruggero D, Santoro MM.
Cell Metab. 2024;36:1945-1962. doi: 10.1016/j.cmet.2024.07.022. - Translational Control of Metabolism and Cell Cycle Progression in Hepatocellular Carcinoma.
Scagliola A, Miluzio A, Biffo S.
Int J Mol Sci. 2023;24. doi: 10.3390/ijms24054885. - Mapping of functional SARS-CoV-2 receptors in human lungs establishes differences in variant binding and SLC1A5 as a viral entry modulator of hACE2.
Miluzio A, Cuomo A, Cordiglieri C, Donnici L, Pesce E, Bombaci M, Conti M, Fasciani A, Terracciano L, Manganaro L, et al.
EBioMedicine. 2023;87:104390. doi: 10.1016/j.ebiom.2022.104390. - FAM46C Is an Interferon-Stimulated Gene That Inhibits Lentiviral Particle Production by Modulating Autophagy.
Mancino M, Lai G, De Grossi F, Cuomo A, Manganaro L, Butta GM, Ferrari I, Vicenzi E, Poli G, Pesce E, et al.
Microbiol Spectr. 2023;11:e0521122. doi: 10.1128/spectrum.05211-22. - Inhibition of eIF6 Activity Reduces Hepatocellular Carcinoma Growth: An In Vivo and In Vitro Study.
Scagliola A, Miluzio A, Mori G, Ricciardi S, Oliveto S, Manfrini N, Biffo S.
Int J Mol Sci. 2022;23. doi: 10.3390/ijms23147720. - Aspartate metabolism in endothelial cells activates the mTORC1 pathway to initiate translation during angiogenesis.
Oberkersch RE, Pontarin G, Astone M, Spizzotin M, Arslanbaeva L, Tosi G, Panieri E, Ricciardi S, Allega MF, Brossa A, et al.
Dev Cell. 2022;57:1241-1256. doi: 10.1016/j.devcel.2022.04.018. - LINE1 are spliced in non-canonical transcript variants to regulate T cell quiescence and exhaustion.
Marasca F, Sinha S, Vadala R, Polimeni B, Ranzani V, Paraboschi EM, Burattin FV, Ghilotti M, Crosti M, Negri ML, et al.
Nat Genet. 2022;54:180-193. doi: 10.1038/s41588-021-00989-7. - Targeting of eIF6-driven translation induces a metabolic rewiring that reduces NAFLD and the consequent evolution to hepatocellular carcinoma.
Scagliola A, Miluzio A, Ventura G, Oliveto S, Cordiglieri C, Manfrini N, Cirino D, Ricciardi S, Valenti L, Baselli G, et al.
Nat Commun. 2021;12:4878. doi: 10.1038/s41467-021-25195-1. - mTOR-dependent translation drives tumor infiltrating CD8(+) effector and CD4(+) Treg cells expansion.
De Ponte Conti B, Miluzio A, Grassi F, Abrignani S, Biffo S, Ricciardi S.
Elife. 2021;10. doi: 10.7554/eLife.69015. - Alternative Splicing Generates a MONOPTEROS Isoform Required for Ovule Development.
Cucinotta M, Cavalleri A, Guazzotti A, Astori C, Manrique S, Bombarely A, Oliveto S, Biffo S, Weijers D, Kater MM, Colombo L.
Curr Biol. 2021;31:892-899. doi: 10.1016/j.cub.2020.11.026. - Clonally expanded EOMES(+) Tr1-like cells in primary and metastatic tumors are associated with disease progression.
Bonnal RJP, Rossetti G, Lugli E, De Simone M, Gruarin P, Brummelman J, Drufuca L, Passaro M, Bason R, Gervasoni F, et al.
Nat Immunol. 2021;22:735-745. doi: 10.1038/s41590-021-00930-4. - Endosomal trafficking and DNA damage checkpoint kinases dictate survival to replication stress by regulating amino acid uptake and protein synthesis.
Ajazi A, Bruhn C, Shubassi G, Lucca C, Ferrari E, Cattaneo A, Bachi A, Manfrini N, Biffo S, Martini E, Minucci S, Vernieri C, Foiani M.
Dev Cell. 2021 Sep 8:S1534-5807(21)00678-X.
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