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

  • Left: autophagy activation in clones induced in the imaginal wing disc. Right: animal size is controlled by Myc expression. Bottom: autophagy activation in fat body cellsCharacterization 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. Left: schematic representation of glutamate-glutamine cycle between neurons and glial cells. Right: brain of drosophila larvae
    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.Left: schematic representation of the infiltration of immune cells in the adipose tissue of obese patients. Right: hemocytes in the fat body of drosophila larvae
    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

A Ph.D. student position is available this year on project 1, please contact the PI.
LM and LT students are welcome to apply for their internship.

Group members

  • Paola Bellosta PI*
  • Valeria Manara PhD student
  • Stefania Santarelli Pre-doc 
  • Alessia Pegoraro student
  • Anna Valerio student

* present 
Adjunct Associate Professor, Dept of Medicine NYU Langone Medical Center, New York, USA
Member of the 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 European Huntington Disease Network
2009-17 Member of the Diabetes and Endocrinology Center (DERC) Columbia University, New York, NY, USA

Ongoing Collaborations

  • Franco Taroni, Cinzia Gellera, Neurological Institute “C. Besta” Milan, Italy
  • Alessandro Provenzani, Ágata S. Carreira, CIBIO, University of Trento, Italy
  • Gabriella Viero, Fondazione Bruno Kessler, Trento, Italy
  • Maria A. Vanoni, University of Milan, Italy
  • Tom Vanden Berghe, Greta Klejborowska, University of Antwerp, Belgium
  • Laura Johnston, Columbia University, NY
  • Hugo Stocker, ETH, Zurich, CH
  • Florenci Serras, University of Barcelona, Spain
  • Adam Bajar, University of South Boemia, Ceske Budejovice, Czech Republic

Selected publications

Santarelli S, Londero C, Soldano A, Candelaresi C, Todeschini L, Vernizzi L, Bellosta P. Front Neurosci. Drosophila melanogaster as a model to study autophagy in neurodegenerative diseases induced by proteinopathies. 2023  May 18;17:1082047. doi: 10.3389/fnins

Vitali T, Vanoni MA, Bellosta P. Quantitation of Glutamine Synthetase 1 Activity in Drosophila melanogaster. Methods Mol Biol. 2023  2675:237-260. doi: 10.1007/978-1-0716-3247-5-18.

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. Reduction of nucleolar NOC1 leads to the accumulation of pre-rRNAs and induces Xrp1, affecting growth and resulting in cell competition.
J Cell Sci. 2022   Dec 1;135(23) jcs260110. doi: 10.1242/jcs.260110.  Cover

Destefanis F, Manara V, Bellosta P. Myc as a Regulator of Ribosome Biogenesis and Cell Competition: A Link to Cancer. Int J Mol Sci. 2020 Jun 5;21(11).

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. Glutamine Synthetase 1 Increases Autophagy Lysosomal Degradation of Mutant Huntingtin Aggregates in Neurons, Ameliorating Motility in a Drosophila Model for Huntington's Disease. Cells. 2020 Jan 13;9(1):196.

Bellosta P*, Soldano A*. Drosophila melanogaster, Dissecting the Genetics of Autism Spectrum Disorders: A Drosophila Perspective. Frontiers in Physiology 2019 Aug 7;1 *corr author.

Mirzoyan Z, Allocca MT, Valenza MA, Sollazzo M, Grifoni D, and Bellosta P. Drosophila melanogaster as a model organism to study cancer growth. Frontiers in Genetics. 2019 Mar 1;10:51.

Valenza A, Bonfanti C, Pasini MA, Bellosta  P. Anti-inflammatory effect of anthocyanins in a Drosophila model of chronic inflammation., Biomed Res Int. 2018 Mar 12;2018.

Di Giacomo S, Sollazzo M, de Biase D, Ragazzi M, Bellosta P, Pession A, Grifoni D. Human Cancer Cells Signal Their Competitive Fitness Through MYC Activity. Sci Rep. 2017 Oct 3;7(1):12568.

Allocca MT, Zola S, Bellosta P. Modeling of Human Diseases using The Fruit Fly, Drosophila Melanogaster. Drosophila melanogaster - Model for Recent Advances in Genetics and Therapeutics InTech Open 2017 ISBN 978-953-51-5484-6.

Paiardi C, Mirzoyan Z, Zola S, Parisi F, Vingiani A, Pasini ME, Bellosta P. Genes (Basel). The Stearoyl-CoA Desaturase-1 (Desat1) in Drosophila cooperates with Myc to Induce Autophagy and Growth, a Potential New Link to Tumor Survival. 2017 Apr 28;8(5).

De la Cova C, Senoo-Matsuda N, Ziosi M, Wu C, Bellosta P. Quinzii CM and Johnston L. Super-competitor status of Drosophila Myc cells requires p53 as a fitness sensor to reprogram metabolism and promote viability. Cell Metabolism 2014  19(3):470-83.

Parisi F, Riccardo S, Zola S, Lora C, Grifoni D, Brown L and Bellosta P. dMyc expression in the fat body affects DILP2 release and increases the expression of the fat desaturase Desat1 resulting in organismal growth. 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. BMC Biol. 2011 Sep 27;9:65.

Parisi F, Riccardo S, Daniel M, Saqcena M, Kundu N, Pession A, Grifoni D, Stocker H, Tabak E, Bellosta P. 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).

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. Identification of domains responsible for ubiquitin-dependent degradation of dMyc by glycogen synthase kinase 3beta and casein kinase 1 kinases. Mol Cell Biol. 2009 Jun;29(12):3424-34. Cover

Bellosta P, Hulf T, Balla Diop S, Usseglio F, Pradel J, Aragnol D, Gallant P. Myc interacts genetically with Tip48/Reptin and Tip49/Pontin to control growth and proliferation during Drosophila development. Proc Natl Acad Sci U S A. 2005 Aug 16;102(33):11799-804.

De la Cova C, Abril M, Bellosta P, Gallant P, Johnston LA. Drosophila myc regulates organ size by inducing cell competition. Cell. 2004 Apr 2;117(1):107-16. Cover

The complete list is available at: https://pubmed.ncbi.nlm.nih.gov/?term=bellosta+p&sort=date