Area di ricerca: Scienze Biomolecolari

"The research activity focuses on elucidating the molecular mechanisms that regulate cell growth, metabolism and longevity with particular emphasis on understanding their dysfunctions associated with human diseases in unicellular and multicellular systems."

Keywords: Cell cycle, metabolism, glucose sensing, lipid metabolism, α-synuclein, protein aggregation, aging, neurodegeneration, astrocytes, Parkinson’s disease, Alzheimer’s disease.

Understanding and Postponing Yeast Death to Improve Production
The yeast Saccharomyces cerevisiae is used in microbial biotechnology to produce various compounds, ranging from ethanol as a biofuel to insulin to treat diabetes. It is furthermore widely used as model organism to study eukaryotic biology, for example mechanisms involved in aging, the cell cycle and regulated cell death. A key-challenge therefore lies in postponing cell death under industrial conditions for as long as possible. In this project, in which seven host international institutes and fifteen associated partners are involved, we aim to identify specific functions in nutrient sensing to improve yeast survival and longevity and to manipulate selected pathways to obtain strains of different yeast species with modified cell death and senescence profiles. This knowledge will be used to improve the bioproduction of chemicals.
(Research project, 2026-2029: HORIZON-MSCA-2024-DN-01, UPsYDE, proposal number 1011227210, https://cordis.europa.eu/project/id/101227210).

Metabolic Regulation and AMPK Functions
The kinase AMPK (AMP-activated protein kinase) is the master regulator of cellular energy homeostasis. We reported that in yeast Snf1/AMPK regulates:
1) cell cycle progression (DOI: 10.4161/cc.9.11.11847; DOI: 10.1016/j.bbamcr.2013.09.014; DOI: 10.1038/s41598-018-24252-y)
2) PKA pathway by phosphorylating adenylate cyclase (DOI: 10.1074/jbc.M115.658005)
3) the TORC1 effectors Sch9 and Pib2 (DOI: 10.7554/eLife.84319)
4) metabolism by sensing glucose flux (through glucose-6-phosphate, G6P) (DOI: 10.3390/ijms22179483)
A novel feedback mechanism regulating Snf1/AMPK activity is currently under investigation. Specifically, we are studying its nuclear enrichment upon glucose depletion as a function of cell cycle progression and its upstream activating kinases.

Plant-Derived Bioactive Compounds against Neurodegeneneration and Lipid Dysmetabolism
As part of the National Biodiversity Future Centre initiative (https://www.nbfc.it/en) research focused on the effects of plant-derived bioactive compounds on aging, protein aggregation associated with neurodegeneration, and lipid metabolism modulation, aiming to identify beneficial molecules and uncover their molecular mechanisms (DOI: 10.1016/j.neurot.2025.e00825; DOI: 10.1016/j.crfs.2024.100888; DOI: 10.3390/nu16091298; DOI: 10.3390/antiox13010093; DOI: 10.3390/nu14204368; DOI: 10.18632/aging.104069). (Research Projects funded by the European Union—NextGenerationEU, National Biodiversity Future Center).

Metabolic Alterations in Alzheimer’s Disease
Post-mortem hippocampal samples from male and female cohorts affected by Alzheimer’s disease (AD), revealed significant differences in metabolic pathways between control and AD groups, with notable sex-specific variations. Serine metabolism is strongly modulated, suggesting distinct pathophysiological mechanisms in males and females. Using hiPSC-derived astrocytes and neurons, we are exploring the role of serine metabolism during astrocyte and neuron differentiation to develop robust cellular models for studying neurodegenerative diseases, with potential applications in therapeutic development (DOI: 10.1016/j.celrep.2022.111271; DOI: 10.1111/febs.16816; DOI: 10.3389/fncel.2025.1616911).

Paola Coccetti, Associate Professor of Biochemistry - Group Leader

room 5013, building U3, tel.: +39 02 6448 3521
lab 5011, building U3, tel. +39 02 6448 3513
paola.coccetti@unimib.it
BtBs profile, UNIMIB profile, Publications (Bicocca Open Archive)
CV, LinkedIn, PubMed,  ResearchGate,  Scopus,  ORCID,  Google Scholar

Farida Tripodi, Associate Professor of Biochemistry

room 5011, building U3, tel. +39 02 6448 3513
lab 5013, building U3, tel. +39 02 6448 3521
farida.tripodi1@unimib.it
BtBs profile, UNIMIB profile, Publications (Bicocca Open Archive)
Google Scholar, LinkedIn

-Hind Moukham, PhD student: hind.moukham@unimib.it

-Andrea Sanguedolce, Master’s thesis student: a.sanguedolce1@campus.unimib.it

-Coccetti P* et al. Acteoside exerts neuroprotective effects by preventing α-synuclein aggregation and oxidative stress in models of Parkinson’s disease. Neurotherapeutics. 2025 Dec 22:e00825. https://doi.org/10.1016/j.neurot.2025.e00825

- Marco Caligaris, Raffaele Nicastro, Zehan Hu, Farida Tripodi, Johannes Erwin Hummel, Benjamin Pillet, Marie-Anne Deprez, Joris Winderickx, Sabine Rospert, Paola Coccetti, Jörn Dengjel, Claudio De Virgilio. Snf1/AMPK fine-tunes TORC1 signaling in response to glucose starvation. Elife. 2023 Feb 7:12:e84319. doi: 10.7554/eLife.84319.

- Elisa Maffioli, Giulia Murtas, Valentina Rabattoni, Beatrice Badone, Farida Tripodi, Filomena Iannuzzi, Danilo Licastro, Simona Nonnis, Anna Maria Rinaldi, Zoraide Motta, Silvia Sacchi, Nadia Canu, Gabriella Tedeschi, Paola Coccetti*, Loredano Pollegioni. Insulin and serine metabolism as sex-specific hallmarks of Alzheimer's disease in the human hippocampus. Cell Rep. 2022 Sep 6;40(10):111271. doi: 10.1016/j.celrep.2022.111271. *Co-corresponding author

-Dual action antifungal small molecule modulates multidrug efflux and TOR signaling. Nat Chem Biol. 2016 Oct;12(10):867-75. DOI: 10.1038/nchembio.2165

Dipartimento di Biotecnologie e Bioscienze (BtBs) - Università degli Studi di Milano-Bicocca, Milano, Italia

last update January 2026