Overview
We study how cells communicate and how changes in their metabolic pathways influence the behavior of neighboring cells. Using the power of Drosophila genetics and the high flexibility and availability of genetic tools, we are using animals carrying models of human diseases including tumors, neuronal degeneration, and of metabolic disorders to analyze how changes in their metabolism may influence growth and survival.
Research directions
Characterization of MYC-induced cell competition and ribosomal biogenesis: a link to tumor growth.
We showed that different levels of Myc induce cell competition, a process that occurs when “winner” cells - with higher rates of protein synthesis and metabolically better fit - grow and expand their domain by actively killing wild-type or “loser” cells. Cell competition plays a crucial role in early tumorigenesis. Dysregulation of ribosome biogenesis and translational activity is also associated with cancer initiation and progression and is also a hallmark of ribosomopathies, rare genetic diseases caused by mutations in ribosomal proteins and rRNA processing factors. Using genetic and proteomic approaches, we identified MYC-regulated genes that control rRNA maturation or ribosomal function, such as NOC1, a new executor of cell competition induced by nucleolar stress. On this line, we are using Drosophila to characterize the MYC-induced nucleolar stress to reveal novel pathways that link ribosome biogenesis, cell competition, and tumor initiation-
Frataxin and ferroptosis: new Drosophila's Friedreich Ataxia (FA) models.
Friedreich's ataxia (FA) is a genetic disease caused by reduced levels of the iron-binding protein frataxin. Iron metabolism and frataxin function are highly conserved between Drosophila and vertebrates, allowing us to generate Drosophila's frataxin models with FRDA-related phenotypes. We are using these different FA fly models to investigate ferroptosis signaling in different organs and to test potential drug candidates for ferroptosis amelioration; these studies will be followed up by patient-derived 3D-organoids. -
Identifying signaling that drives autophagy to ameliorate proteinopathies.
In the brain, glutamate is maintained at the physiological level by a non-autonomous cycle between glia and neurons called the “glutamate-glutamine cycle” (GGC), often unbalanced in patients with Neuronal Degeneration Diseases (NDD). To understand how the GGC controls neuronal survival, and which signaling factors between glial, and neurons lead to cell survival in NDD, we modulate, in neurons or glia, the expression of key enzymes that control the GGC, using Drosophila models for polyglutamine-related diseases like Huntington’s Disease (HD), Spinocerebellar Ataxias (SCAs) and Amyotrophic Lateral sclerosis (ALS). We found that manipulating enzymes that control the GGC activates autophagy, which is fundamental for neuronal survival. Using genetic and metabolomic approaches, we are currently determining the molecular mechanisms activating autophagy in vivo, leading to the reduction of toxic protein aggregates. -
Chronic inflammation in a model of obesity and T2D.
In obese individuals, immune cells infiltrate the adipose tissue promoting low-grade chronic inflammation or Adipocyte Tissue Macrophages (ATM). This status has been linked to altered adipocyte metabolic function and induced insulin resistance. Using Drosophila, where the functional relationship between immune cells, hemocytes (macrophage-like), and larval fat body (FB) is conserved, we demonstrated that edible bio-components like antioxidants and anti-diabetic drugs decrease chronic inflammation and ameliorate insulin resistance. We identified that eiger/TNFa signaling, among others, is relevant for recruiting hemocytes in the adipose cells, suggesting that key conditions described in human obesity and metabolic disorders are conserved in our model. We are currently screening (genetic and chemical) for anti-diabetic drugs that can ameliorate insulin resistance in our models.
Positions available
Internship applications are welcome from Master’s and Bachelor’s students.
For PhD applications, please contact the PI.
Group members
- Paola Bellosta, PI*
- Shivani Bajaj, PhD student
- Alessandra Caragiuli, MA 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
Isoform-Specific Activation of p53B and p53C in Response to Nucleolar Stress in Drosophila wing imaginal discs. Vutera Cuda A, Shivani Bajaj S, Manara V, Bellosta P.
bioRxiv. 2025 Aug 11:2025.
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