Overview
Our lab investigates conserved stress signaling pathways, such as nucleolar stress, including autophagy, ferroptosis, lipid metabolism, and inflammation, that regulate cell fitness and survival. Using Drosophila disease models and human cell systems, we link metabolic remodeling and intercellular communication to mechanisms that translate to human disease, with a particular focus on cancer.
Research directions
Nucleolar Stress and Its Control on Cell Growth
Alterations in ribosome biogenesis induce nucleolar stress, promoting cell competition and supporting early tumor development. Dysregulation of ribosome biogenesis and translational control is a hallmark of cancer and of ribosomopathies, rare genetic disorders associated with a high incidence of tumors. Using genetic and proteomic approaches, we identified Noc1 as a MYC-regulated factor that controls rRNA maturation and ribosomal function. Noc1 is a component of a conserved family of nucleolar proteins that, together with Noc2 and Noc3, regulates rRNA maturation and processing. Their expression is essential for cancer cells, and Noc1 downregulation induces nucleolar stress, increases p53 levels, and triggers apoptosis associated with DNA damage through mechanisms that remain to be fully defined.
Our findings underscore nucleolar stress and the NOC genes as regulators of a novel growth-control mechanism in flies. We are exploiting alterations in NOC proteins and their human homologues in tumors to uncover how their function may influence key growth-regulatory genes, including MYC, and how this regulation impacts genome integrity and tumor development.
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Ferroptosis and Chronic Inflammation: Antioxidant Strategies Targeting Stress Signaling Pathways
Using Friedreich’s ataxia (FA) as a model of lipid peroxidation and ferroptosis, we investigate how alterations in iron and lipid metabolism in metabolic tissue in the brain generate oxidative stress and reactive oxygen species (ROS) that activate ferroptotic signaling. Leveraging conserved Drosophila FA models and human cell systems, we test antioxidant compounds, including naturally occurring plant-derived extracts, to identify stress-signaling pathways that suppress lipid peroxidation, limit ferroptotic damage, and promote cell survival.
In parallel, we use Drosophila models with conserved immune–metabolic interactions to study obesity-associated chronic inflammation and insulin resistance in metabolic tissues, conditions driven by oxidative and metabolic stress. Edible bio-components, such as antioxidants and anti-diabetic agents, reduce chronic inflammation and improve insulin sensitivity. We are currently performing chemical screens to identify novel antioxidant-based strategies that alleviate metabolic stress and insulin resistance. -
Autophagy as a Survival Mechanism
Using Huntington’s disease (HD) as a model of proteinopathies, we investigate how proteotoxic stress disrupts cellular homeostasis and how this stress can be counteracted through the induction of autophagy. By modulating amino acid/TOR signaling and metabolic pathways, we activate autophagy as an adaptive anti-stress response. Using genetic and biochemical approaches, we aim to define the mechanisms through which autophagy in vivo reduces toxic protein aggregates and enhances cellular resilience, with the goal of extending this understanding to other chronic stress conditions.
Group members
- Paola Bellosta, PI*
- Shivani Bajaj, PhD student
- Alessandra Caragiuli, MA student
- Giorgia Depaoli, MA student
- Sara Miglioranza, BA student
- Lorenzo Conci, BA student
- Federico Ghirelli, BA student
*Present
Adjunct Associate Professor, Department of Medicine, NYU Langone Medical Centre, New York, USA
Member of COST-21154 Translational Control in Cancer European Network
Member of the Drosophila European Network http//droseu.net
2018-22 Member of the Scientific Advisory Committee of the European Huntington's Disease Network
2009-17 Member of the Diabetes and Endocrinology Research Centre (DERC) Columbia University, New York, NY, USA
Ongoing Collaborations
- Stefan Martens, Fondazione Edmund Mach, FEM Trento
- Giovanni Provenzano, Dept CIBIO, University of Trento
- Alessandro Provenzani, Dept CIBIO, University of Trento
- Gabriella Viero, Fondazione Bruno Kessler, FBK Trento
- Marianna Penzo, Hospital Sant’Orsola and University of Bologna
- Giovanni Bertalot, Hospital Santa Chiara, and CisMed, Trento
- Adam Bajar, University of South Bohemia, Ceske Budejovice, Czech Republic
Selected publications
Noc1 Reduction Induces Nucleolar Stress and Upregulates p53 Isoforms, with a Robust Increase of the Truncated p53E Isoform in Drosophila Wing Discs. Vutera Cuda A, Shivani Bajaj S, Manara V, Bellosta P. G3 (Bethesda). December 2025 accepted.
Drosophila and human cell studies reveal a conserved role for CEBPZ, NOC2L, and NOC3L in rRNA processing and tumorigenesis. Rambaldelli G, Manara V, Vutera Cuda A, Bertalot G, Penzo M, Bellosta P.
J Cell Sci 2025 2025 Sep 1;138(17)
Optimized protocol for single-cell isolation and alkaline comet assay to detect DNA damage in cells of Drosophila wing imaginal discs. Pederzolli M, Barion E, Valerio A, Cuda AV, Manara V, Bellosta P.
STAR Protoc. 2025 Jan 23;6(1):103590.
Drosophila: a Tale of regeneration with MYC. Serras F., Bellosta P.
Front Cell Dev Biol. 2024 Jul 23;12:1429322.
NOC1 is a direct MYC target, and its protein interactome dissects its activity in controlling nucleolar function. Manara V, Radoani M, Belli R, Peroni D, Destefanis F, Angheben L, Tome G, Tebaldi T, Bellosta P.
Front Cell Dev Biol. 2023 Dec 28;11:1293420.
Drosophila melanogaster as a model to study autophagy in neurodegenerative diseases induced by proteinopathies. Santarelli S, Londero C, Soldano A, Candelaresi C, Todeschini L, Vernizzi L, Bellosta P.
Front Neurosci. 2023 May 18;17:1082047.
Reduction of nucleolar NOC1 leads to the accumulation of pre-rRNAs and induces Xrp1, affecting growth and resulting in cell competition. Destefanis F, Manara V, Santarelli S, Zola S, Brambilla M, Viola G, Maragno P, I. Signoria, Viero G, Pasini ME, Penzo M and Bellosta P.
J Cell Sci. 2022 Dec 1;135(23)
Myc as a Regulator of Ribosome Biogenesis and Cell Competition: A Link to Cancer. Destefanis F, Manara V, Bellosta P.
Int J Mol Sci. 2020 Jun 5;21(11).
Glutamine Synthetase 1 Increases Autophagy Lysosomal Degradation of Mutant Huntingtin Aggregates in Neurons, Ameliorating Motility in a Drosophila Model for Huntington's Disease. Vernizzi L, Paiardi C, Licata G, Vitali T, Santarelli S, Raneli M, Manelli V, Rizzetto M, Gioria M, Pasini ME, Grifoni D, Vanoni MA, Gellera C, Taroni F, Bellosta P.
Cells. 2020 Jan 13;9(1):196.
Drosophila melanogaster as a model organism to study cancer growth. Mirzoyan Z, Allocca MT, Valenza MA, Sollazzo M, Grifoni D e Bellosta P.
Frontiers in Genetics. 2019 Mar 1;10:51.
Human Cancer Cells Signal Their Competitive Fitness Through MYC Activity. Di Giacomo S, Sollazzo M, de Biase D, Ragazzi M, Bellosta P, Pession A, Grifoni D.,
Sci Rep. 2017 Oct 3;7(1):12568.
The Stearoyl-CoA Desaturase-1 (Desat1) in Drosophila cooperates with Myc to Induce Autophagy and Growth, a Potential New Link to Tumor Survival. Paiardi C, Mirzoyan Z, Zola S, Parisi F, Vingiani A, Pasini ME, Bellosta P.
Genes (Basel). 2017 Apr 28;8(5).
Super-competitor status of Drosophila Myc cells requires p53 as a fitness sensor to reprogram metabolism and promote viability. de la Cova C, Senoo-Matsuda N, Ziosi M, Wu C, Bellosta P, Quinzii CM, and Johnston L.
Cell Metabolism 2014 19(3):470-83.
dMyc expression in the fat body affects DILP2 release and increases the expression of the fat desaturase Desat1, resulting in organismal growth. Parisi F, Riccardo S, Zola S, Lora C, Grifoni D, Brown L, and Bellosta P.
Dev Biol. 2013 379(1):64-75 F1000Prime.
Drosophila insulin and target of rapamycin (TOR) pathways regulate GSK3 beta activity to control Myc stability and determine Myc expression in vivo. Parisi F, Riccardo S, Daniel M, Saqcena M, Kundu N, Pession A, Grifoni D, Stocker H, Tabak E, Bellosta P.
BMC Biol. 2011 Sep 27;9:65.
dMyc functions downstream of Yorkie to promote the supercompetitive behavior of hippo pathway mutant cells. Ziosi M, Baena-López LA, Grifoni D, Froldi F, Pession A, Garoia F, Trotta V, Bellosta P, Cavicchi S, Pession A. PLoS Genet. 2010 Sep 23;6(9).
Identification of domains responsible for ubiquitin-dependent degradation of dMyc by glycogen synthase kinase 3beta and casein kinase 1 kinases. Galletti M, Riccardo S, Parisi F, Lora C, Saqcena MK, Rivas L, Wong B, Serra A, Serras F, Grifoni D, Pelicci P, Jiang J, Bellosta P.
Mol Cell Biol. 2009 Jun;29(12):3424-34.
Myc interacts genetically with Tip48/Reptin and Tip49/Pontin to control growth and proliferation during Drosophila development. Bellosta P, Hulf T, Balla Diop S, Usseglio F, Pradel J, Aragnol D, Gallant P.
Proc Natl Acad Sci U S A. 2005 Aug 16;102(33):11799-804.
Drosophila myc regulates organ size by inducing cell competition. de la Cova C, Abril M, Bellosta P, Gallant P, Johnston LA.
Cell. 2004 Apr 2;117(1):107-16. Cover