Research Areas: Muscle Biology and Pathology
Keywords: Muscle metabolism, Cell cycle regulators, muscular dystrophy
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.
- 1973 Graduated from High School
- 1979 Degree in Biological Sciences (cum laude), University of Naples “Federico II°”, Italy.
- 1980 Post-doctoral fellow, Unitè de Genie Genetique, Institut Pasteur, Paris (France)
- 1981-1982 Post-doctoral fellow, Department of Microbiology, University of Chicago, Chicago (USA)
- 1982-1984 Post-doctoral fellow, Department of Pathology, New York University School of Medicine, New York (USA)
- 1984-1985 Research fellow, National Research Council, Institute of Genetics and Biophysics, Napoli (Italy)
- 1985-1990 Research fellow, University “La Sapienza”, Department of Human Biopathology, Roma (Italy)
- 1990-2001 Research Scientist – National Research Council, Institute of Cell Biology, Roma, Italy
- 2001-present Senior Research Scientist – National Research Council, Institute of Neurobiology and Moleculare Medicine, Institute of Cell Biology and Neurobiology and Institute of Biochemistry and Cell Biology Roma, Italy
1979: “Ernesto Scoffone and Terenzio Cremona” Thesis Award, sponsored by the Italian Society of Biophysics and Molecular Biology
1980: Research Fellowship Award from Fondazione “Istituto Pasteur-Fondazione Cenci- Bolognetti”
Teaching and Professional activities:
2005-2013 Teaching Board Member, PhD School in “Genetics and Cellular Biology”, Tuscia University, Viterbo, Italy
2013 Member of Grant Review Committee “Future in Research 2013”. Ministry of University and Research (MIUR)
2014 Member of Grant Review Committee “SIR” (Scientific Independence of young Researchers). Ministry of University and Research (MIUR)
Ad hoc peer reviewer for several scientific journals, including Stem Cells, Cell Death Differentiation, Experimental Cell Research, Journal of Cellular Biochemistry, Biochemistry and Cell Biology
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.
View all publications
- 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.
- Giannattasio, S, Giacovazzo, G, Bonato, A, Caruso, C, Luvisetto, S, Coccurello, R, Caruso, M. (2018) Lack of cyclin D3 induces skeletal muscle fiber-type shifting, increased endurance performance and hypermetabolism. Sci Rep., 8: 12792.
- Albini, S, Coutinho Toto, P, Dall’Agnese, A, Malecova, B, Cenciarelli, C, Felsani, A, Caruso, M, Bultman, SJ, Puri, PL. (2015) Brahma is required for cell cycle arrest and late muscle gene expression during skeletal myogenesis. EMBO Rep., 16:1037-50.
- De Luca, G, Ferretti, R, Bruschi, M, Mezzaroma, E, Caruso, M. (2013) Cyclin D3 critically regulates the balance between self-renewal and differentiation in skeletal muscle stem cells. Stem Cells, 31: 2478–2491.
- Micheli, L, Leonardi, L, Conti, F, Maresca, G, Colazingari, S, Mattei, E, Lira SA, Farioli- Vecchioli, S, Caruso, M, Tirone, F. (2011) PC4/Tis7/IFRD1 stimulates skeletal muscle regeneration and is involved in myoblast differentiation as a regulator of MyoD and NF-kB. J. Biol. Chem. 286: 5691-5707.
- Marinelli, S, Luvisetto, S, Cobianchi, S, Makuch, W, Obara, I, Mezzaroma, E,Caruso, M, Straface, E, Przewlocka, B, Pavone F. (2010) Botulinum neurotoxin type A counteracts neuropathic pain and facilitates functional recovery after peripheral nerve injury in animal models. Neuroscience, 171: 316-328.
- 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.
- Micheli, L, Leonardi, L, Conti, F, Buanne, P, Canu, N, Caruso, M, Tirone, F. (2005) PC4 coactivates MyoD by relieving the histone deacetylase 4-mediated inhibition of myocyte enhancer factor 2C. Mol.Cell.Biol., 25:2242-59.
- Magenta, A, Cenciarelli, C, De Santa, F, Fuschi, P, Martelli, F, Caruso, M.*, Felsani, A. (2003) MyoD Stimulates RB Promoter Activity via the CREB/p300 Nuclear Transduction Pathway. Mol.Cell.Biol., 23:2893-2906. * corresponding author
- Guardavaccaro, D, Corrente, G, Covone, F, Micheli, L, D’Agnano, I, Starace, G, Caruso, M, Tirone, F. (2000) Arrest of G1-S Progression by the p53-inducible Gene PC3 is Rb-dependent and Relies on the Inhibition of Cyclin D1 Expression. Mol. Cell. Biol., 20:1797-1815.
- De Fiore, B, Palena, A, Felsani, A, Palitti, F, Caruso, M, Lavia, P. (1999) Cytosine methylation transforms an E2F site in the retinoblastoma gene promoter into a binding site for the general repressor methylcytosine- binding protein 2 (MeCP2). Nucleic Acid Res., 27:2852-2859.
- Cenciarelli, C, De Santa, F, Puri, PL, Mattei, E, Ricci, L, Bucci, F, Felsani, A, Caruso, M. (1999) Critical Role Played by Cyclin D3 in the MyoD-Mediated Arrest of Cell Cycle during Myoblast Differentiation. Mol. Cell Biol., 19:5203-5217.
- Martelli, F, Iacobini, C, Caruso, M, and Felsani, A. (1996). Characterization of two novel YY1 binding sites in the polyomavirus late promoter. J. Virol., 70:1433-1438.
- Yuan, W, Condorelli, G, Caruso, M, Felsani, A, Giordano, A. (1996) Human p300 protein is a coactivator for the transcription factor MyoD. J. Biol. Chem., 271:9009-9013.
- Martelli, F, Cenciarelli, C, Polikar, B, Santarelli, G, Bevilacqua, P, Caruso, M, Felsani, A. (1995) Relationships between MyoD and Rb1 in myogenesis. In Future Trends in Endocrinology, A. de Bellis and E. Schipani, eds. (Rome: Ares-Serono Symposia Publications), pp. 233-250.
- Tedesco, D, Caruso, M, Fischer-Fantuzzi, L, and Vesco, C. (1995) The inhibition of cultured myoblast differentiation by the SV40 large T antigen occurs after myogenin expression and Rb upregulation, and is not exerted by transformation-competent cytoplasmic mutants. J. Virol.,69:6947-6957.
- Martelli, F, Cenciarelli, C, Santarelli, G, Polikar, B, Felsani, A, Caruso, M. (1994) MyoD induces retinoblastoma gene expression during myogenic differentiation. Oncogene, 9:3579-3590
- Caruso, M, Martelli, F, Giordano, A, and Felsani, A. (1993) Regulation of MyoD gene transcription and protein function by the transforming domains of the adenovirus E1A oncoprotein. Oncogene, 8:267-278.
- Caruso, M, Iacobini, C, Passananti, C, Felsani, A, Amati, P. (1990) Protein recognition sites in Polyomavirus enhancer: formation of a novel site for NF-1 factor in an enhancer mutant and characterization of a site in the enhancer D domain. EMBO J., 9:947-955.
- Passananti, C, Felsani, A, Caruso, M, Amati, P. (1989) Mouse genes coding for zinc-finger containing proteins: characterization and expression in differentiated cells. Proc. Nat. Acad. Sci. USA, 86:9417- 9421.
- Maione, R, Felsani, A, Pozzi, L, Caruso, M, Amati, P. (1989) Polyomavirus genome and Polyomavirus enhancer-driven gene expression during myogenesis. J. Virol., 63:4890-4897.
- Caruso, M, Sacco, M, Medoff, G, Maresca, B. (1987) Heat shock 70 gene is differentially expressed in H. capsulatum strains with different levels of thermotolerance and pathogenicity. Molecular Microbiology, 1:151-158.
- Caruso, M, Felsani, A, Amati, P. (1986) Sites hypersensitive to and protected from nuclease digestion in the regulatory region of wild type and mutant Polyoma chromatin. EMBO J., 5:3539- 3546.
- Liboi, E, Caruso, M, Basilico, C. (1984) New rat cell line that is highly susceptible to transformation by several oncogenes. Mol. Cell. Biol., 4:2925-2928.
- Caruso, M and Shapiro, JA (1982) Interactions of Tn7 and temperate phage F116L of Peudomonas aeruginosa. Molecular and General Genetics, 188:292-298.
- Shapiro, JA, Charbit, A, Benson, S, Caruso, M, Laux, R, Meyer, R, Banuett, F (1982) Perspectives for the genetics engineering of hydrocarbon oxidizing bacteria. Basic Life Sci., 19:243-272.
- Pulitzer, J, Coppo, A, Caruso, M. (1979) Host-virus interactions in control of T4 prereplicative transcription. II. Interactions between tabC (Rho) mutants and T4 mot mutants. J. Mol. Biol., 135:979-997.
- Caruso, M, Coppo, A, Manzi, A, Pulitzer, J. (1979) Host-virus interactions in the control of T4 prereplicative transcription. I. tabC (Rho) mutants. J. Mol. Biol., 135:959-977.
Graduate student (Università Tuscia, VT)
Graduate student (Università Sapienza, RM)
2020-2023 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
18/10/2018. Ciclina D3: la sua assenza rende resistenti alla fatica muscolare.
La mancanza di questa proteina fa prevalere le fibre muscolari che si contraggono lentamente su quelle a contrazione più rapida. Gli animali che ne sono sprovvisti hanno maggior resistenza all’affaticamento ed un maggiore dispendio energetico, con conseguenze sul metabolismo. Ad indicarlo uno studio dell’Istituto di biologia cellulare e neurobiologia del Cnr pubblicato su Scientific Reports