A long-standing interest in our lab is centered on the cross-talk between cell cycle regulation and the differentiation program of skeletal muscle stem cells, which are responsible of post-natal muscle growth and regeneration. A specific attention is given to the role played by the mitogen-induced D-type cyclins, the regulatory subunits of the cyclin-dependent kinases CDK4 and CDK6 that drive progression through the G1 phase of the cell cycle. In addition to their well-known function in cell proliferation, there is increasing evidence that D-type cyclins play important roles in the control of metabolic processes.
Skeletal muscles are composed of heterogeneous myofibers that differ in their contractile response to motor nerve action (slow or fast) and metabolism (oxidative or glycolytic). In this context, we have recently discovered a novel function for cyclin D3 in regulating muscle fiber type phenotype and whole-body energy metabolism. In fact, mice lacking cyclin D3 display an increased proportion of myofibers with high oxidative capacity, increased energy expenditure and running endurance and enhanced fatty acid oxidation.
The main focus of our research is to evaluate the role of cyclin D3 in modulating signaling pathways that modify the metabolic and contractile properties of skeletal muscle fibers in response to functional demands and physiopathological conditions, such as exercise, nutritional challenges, aging, muscle disease. These issues are addressed by functionally inactivating cyclin D3, either genetically or by using specific inhibitors, in normal or dystrophic mouse models. The goal of our research is to define whether cyclin D3 may represent a potential therapeutic target in the treatment of muscular dystrophy and age-associated myopathy.
A related research interest is the investigation of a potential role of natural bioactive dietary compounds, targeting pathways responsible for energy metabolism, in the prevention of age-associated muscle dysfunctions.
Belli R, Bonato A, De Angelis L, Mirabilii S, Ricciardi MR, Tafuri A, Molfino A, Leigheb M, Costelli P, Caruso M, Muscaritoli M and Ferraro E. (2019) Metabolic Reprogramming Promotes Myogenesis During Aging. Frontiers in Physiology. 10:897. doi: 10.3389/fphys.2019.00897.
Giannattasio S, Giacovazzo G, Bonato A, Caruso C, Luvisetto S, Coccurello R and Caruso M. (2018) Lack of cyclin D3 induces skeletal muscle fiber-type shifting, increased endurance performance and hypermetabolism. Scientific Reports. 8:12792.doi: 10.1038/s41598-018-31090-5
Albini, S., Coutinho Toto, P., Dall’Agnese, A., Malecova, B., Cenciarelli, C., Felsani, A., Caruso, M., Bultman, S.J., Puri, PL. (2015) Brahma is required for cell cycle arrest and late muscle gene expression during skeletal myogenesis. EMBO Rep., 16:1037-50. doi: 10.15252/embr.201540159).
De Luca G, Ferretti R, Bruschi M, Mezzaroma E and Caruso M. (2013) Cyclin D3 critically regulates the balance between self-renewal and differentiation in skeletal muscle stem cells. Stem Cells 31: 2478-2491.
De Santa, F.,Albini, S., Mezzaroma, E., Baron, L., Felsani, A, Caruso, M. (2007) pRb-Dependent Cyclin D3 Protein Stabilization Is Required for Myogenic Differentiation. Mol.Cell.Biol. 27: 7248-7265.
Agnese Bonato (email: firstname.lastname@example.org)
Livio Baron (email: email@example.com)
Programs & resourcers
2020-2022 Principal investigator of the project: “Evaluation of cyclin D3 as a potential target to remodel dystrophic muscle toward the slow, oxidative phenotype”, supported by Duchenne Parent Project, Netherlands
2009-2013 Principal investigator of the Telethon project N. GGP08126: “Role of cyclin D3 in satellite cell function and muscle regeneration”, supported by Telethon
2003-2006 Head of Research Unit of the coordinated Project: “Dynamic analysis of differentiation pathways activated by different growth factors in stem cells”, supported by MIURFIRB (project RBAU01PCRL), coordinator: Dr. Luigi Aloe.
2000-2003 Head of Research Unit of the coordinated EU Project: “Histone acetyl-transferases and deacetylases: new targets for cancer therapy”, supported by European Community FP5 (grant QLG1-CT-1999-00866), coordinator: Dr. A.Harel-Bellan, Villejuif, France
1999-2002 Principal investigator of the Telethon project N.1247: “Role of MyoD-induced cell cycle genes in the proliferation, cell cycle arrest and differentiation of muscle satellite cells“, supported Telethon
1995-1997 Co-responsible of the project: “Oncosuppressor genes and cellular differentiation”, supported by AIRC
1993 Principal investigator of the Telethon project N.298: “Control of gene expression in muscle differentiation”, supported by Telethon
1992-1994 Co-responsible of the Project: “Tumor-suppressor genes and differentiation-regulatory genes”, supported by AIRC