Overview | Research directions | Group members | Collaborations | Selected Publications


In our lab we are studying how cell 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 model 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

  • The role of Myc on growth and in tumor: cell competition
    Developing tumors are subjected to nutrient limitations, thus tumor cells reprogram their metabolic pathways to allow a better grow. One of the genes that control these mechanisms is the proto-oncogene c-myc. Expression of Myc activates survival pathways, including autophagy, a self eating process induced when nutrients are reduced, and cell-competition, a process described first for ribosomal proteins, that occurs when cells that are metabolically better fit or “winner” grow near wild-type “loser” cells with lower levels of Myc. These winner cells acquire a super-competitor condition and the ability to induce the death of the slower-growing cells. A similar event is described during the initial steps of cancerization when tumor-promoting genes in precancerous cells give a growth advantaged to the cells causing them to act as winners and to eliminate non-cancerous cells (losers). With genomics and proteomics approaches we found novel members of the ribosomal machinery and of lipid metabolism that we are currently characterizing for their role in myc-induced cell competition.
  • The role of Myc in tumors of the gut
    Drosophila adult adult midgut is a well-established model to study the mechanisms responsible for differentiation and proliferation of the intestinal stem cell-niche as well as to study the relationship between the microbiome and stress related diseases causing inflammation and tumor progression. We previously underpinned pathways that control Myc protein stability; in addition we identify components of the deubiquitinase machinery responsible for controlling Myc expression and proliferation of the gut stem cells. Our aim is to characterize their role in controlling Myc activity.
  • The pathogenesis of many neuronal degeneration (NDD) diseases is mediated by metabolic changes, including increase in glutamate, mitochondria dysfunction resulting in cell death
    Excess of glutamate is maintained at physiological level by a non-autonomous cycle between glia and neurons called “glutamate-glutamine cycle”. Glutamate removal from the synaptic cleft by glial cells is reduced in a model and patients with NDD, suggesting that glia cells actively participate in the survival of neurons. But how the glutamate-glutamine cycle contributes to the mechanisms of neuronal death? And which are the signaling molecules responsible for the cross talk between neurons and glial cells leading to neuronal survival? To answer these questions we manipulate, in neurons or glia, the expression of the key enzymes that control the “glutamate-glutamine” cycle in Drosophila models that have been successfully employed t o dissect the cellular and molecular events in polyglutamine-related diseases like Huntington’s Disease (HD), Spinocerebellar Ataxias (SCAs) and Amyotrophic Lateral sclerosis (ALS). Our preliminary data suggest a key function for GS1 and GDH in ameliorating animal motility and neuronal loss in a Drosophila model for HD resulting in the activation of autophagy, a self-cleaning process fundamental for neuronal survival.
  • In obese people the recruitment of immune cells (macrophages) to adipose tissue (Adipocyte Tissue Macrophages, ATMs) induces a low-grade of chronic inflammation
    This status has been also linked to altered adipocyte metabolic function and to perturbations in lipid metabolism. To study the mechanisms that control chronic inflammation, we are taking advantage the conserved functional relationship in Drosophila between the immune cells, called hemocytes (macrophage like cells) and the larval fat body (which as similar function of the liver and adipose tissue). Using different model for obesity, we are currently studying the relevance of the classic cytokines pathways to ATM, as well as intervene using bioactive food like polyphenolic compounds, derived from fruits and vegetables, which we found to exert a strong protective action against obesity and adipose inflammation.

Group members

  • Paola Bellosta, PI
  • Zhasmine Mirzoyan, Postdoc fellow
  • Francesca Destefanis, PhD student
  • Stefania Santarelli, Student
  • Nicholas Ferrari, student
  • Alessandra Tomasi, Student
  • Federica Gardener, Student

Positions are available for motivated Master and PhD students, please contact the PI


  • Franco Taroni, Cinzia Gellera and Caterina Mariotti Neurological Institute “C. Besta” Milan, IT
  • Maria Antonietta Vanoni University of Milan, IT
  • Elena Cattaneo and Chiara Zuccato University of Milan, IT
  • Carlo Alessandro Cavallotti Polytechnic of Milan,IT
  • Daniela Grifoni University of Bologna, IT
  • Maria Pasini University of Milan, IT
  • Hugo Stocker ETH-Zurich, Switzerland
  • Florenci Serras University of Barcelona, ES
  • Laura Johnston Columbia University, New York, USA
  • Ann Marie Schmidt NYU Langone Medical Center New York, NY, USA
  • Esteban Tabak, Courant Mathematics Institute, NYU, New York, USA

Selected publications

Mirzoyan Z, Sollazzo M, Allocca M, Valenza A,  Grifoni D and Bellosta P  Drosophila melanogaster: a model organism to study cancer. 2019 Frontiers of Genetics - accepted

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;2018:6413172

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. PMID: 28974715

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

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) PMID 28452935

Drosophila Myc: a master regulator of cellular performance. Grifoni D and Bellosta P. Review
Gene Regulatory Mechanisms 2015 Jul 8. pii: S1874 PMID: 25010747

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. PMID: 24561262

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 PMID23608455. selected for 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.PMID: 21951762

Myc Function in Drosophila. Bellosta P, Gallant P. Review Genes Cancer. 2010 Jun 1;1(6):542-546.PMID:21072325

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). doi:pii: e1001140. PMID:20885789

The lethal giant larvae tumour suppressor mutation requires dMyc oncoprotein to promote clonal malignancy. Froldi F, Ziosi M, Garoia F, Pession A, Grzeschik NA, Bellosta P, Strand D, Richardson HE, Pession A, Grifoni D. BMC Biol. 2010 Apr 7;8:33. PMID:20374622

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. PMID:19364825 Cover

aPKCzeta cortical loading is associated with Lgl cytoplasmic release and tumor growth in Drosophila and human epithelia. Grifoni D, Garoia F, Bellosta P, Parisi F, De Biase D, Collina G, Strand D, Cavicchi S, Pession
A. Oncogene. 2007 Aug 30;26(40):5960-5. Epub 2007 Mar 19. PMID:17369850

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.PMID:16087886

Whole-genome analysis reveals a strong positional bias of conserved dMyc-dependent E-boxes. Hulf T, Bellosta P, Furrer M, Steiger D, Svensson D, Barbour A, Gallant P.
Mol Cell Biol. 2005 May;25(9):3401-10. PMID:15831447

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. PMID:15066286 Cover

Please see www.paolabellosta.com for a complete list of publications with links to pdf files.