Our research activity is focused on the molecular basis of stem cell pluripotency and lineage specification in mammals. The main interest of our laboratory is to understand how to direct stem cell differentiation along specific pathways and to develop molecular tools to target tumour initiating cells.  Toward this end, we are engaged in three related projects

Regulation of pluripotent stem cell differentiation by Cripto and Cripto-responsive genes. Most of our research activity is centred on the signalling molecule Cripto, a modulator of members of TGF-β family, which was originally discovered by Graziella Persico at the IGB. In addition to investigating the fundamental biology of mouse ESCs, we are developing molecular tools to target Cripto signalling and improve the use of stem cell-based therapy in neurodegenerative diseases, such as Parkinson’s disease.

Unravelling the role of Cripto in adult tissue regeneration. We discovered that Cripto is re-expressed during muscle regeneration and it is a regulator of the muscle stem cell compartment. We are performing basic molecular studies, both in vitro and in vivo, to unravel the precise nature of Cripto signalling in skeletal muscle regeneration and developing molecular tools to assess the potential therapeutic value of Cripto in alleviating muscle diseases.

Metabolic control of stem cell plasticity. It is now becoming evident that metabolism is a key regulator of stem cell plasticity that has been largely overlooked so far. We have recently contributed to this emerging field showing that the nonessential amino acid (NEAA) L-Proline (L-Pro) acts as an epigenetic signal and is a key regulator of mouse ESC metastability. We are currently investigating the molecular connection between L-proline metabolism and epigenetic modifications in the control of stem cell identity.  

EDUCATION:

1989       Degree in Biological Sciences, University at Naples, (summa cum laude)

1997        Ph.D. in Molecular and Cellular Genetics, Medical School, University of Naples “Federico II”.

RESEARCH APPOINTMENTS:

2007-present          CNR Senior Research Scientist

2004                      Co-founder of the Stem Cell Fate Laboratory at the IGB-ABT, CNR.

2004- present        Group leader at the IGB-ABT, CNR, Naples, Italy.

2004- 2008            Coordinator of Optical Microscopy Facility at the IGB-ABT, CNR.

1998- 2007            Research Scientist at IGB-ABT, CNR, Naples, Italy.

MEMBERSHIPS IN SCIENTIFIC SOCIETIES/COMMITTEES:

1990-present        “Ordine Nazionale dei Biologi” (044967)

2004-present        International Society for Stem Cell Research (ISSCR)

2005-present        “Società Italiana Biofisica e Biologia Molecolare” (SIBBM)

2005- 2008          Executive Committee of the SIBBM

COURSES/MEETINGS CO-ORGANIZER:

2006    EMBO Workshop - Cell Migration, Tissue Invasion and Disease, Capri, Italy

2006    Stem Cell Differentiation Training Course, 1st edition, IGB, Naples, Italy

2007    Stem Cell Differentiation Training Course, 2nd edition, IGB, Naples, Italy

2008    Stem Cell Differentiation Training Course, 3rd edition, IGB, Naples, Italy

2009    SIBBM Meeting: Frontiers in Molecular Biology, Naples, Italy

2009    Stem Cell Differentiation Training Course, 4th edition IGB, Naples, Italy

2009    IGB Workshop – Stem Cells: from Molecular Physiology to therapeutic applications, Capri, Italy

AD HOC REVIEWER (JOURNALS & GRANT AGENCIES):
- Oncogene, Stem Cells, Journal of Cell Physiology, Gene, FEBS Letter, International Journal of Biochemnistry and Cell Biology, BMC-Developmental Biology, Expert Opinion on Therapeutic Targets, PathoGenetics

-Agenzia Spaziale Italiana-Life Science, Agence National de la Recherche Francaise (ANM).

PATENTS
1.    WO2004/083375        
    “Method for promoting the differentiation of stem cells”
    Inventors: G. Minchiotti, M.Graziella Persico and Silvia Parisi,
2.    WO2008/028888    
    “Means and methods for the stimulation of skeletal muscle regeneration”
    Inventors: G. Minchiotti and P. Carmeliet

 

Selected (5 years)

• Liu Y, Kaneda R, Leja TW, Subkhankulova T, Tolmachov O, Minchiotti G, Schwartz RJ, Barahona M, Schneider MD. Hhex and Cer1 mediate the Sox17 pathway for cardiac mesoderm formation in embryonic stem cells. Stem Cells. 2014 Jun;32(6):1515-26.
• Coppola A, Romito A, Borel C, Gehrig C, Gagnebin M, Falconnet E, Izzo A, Altucci L, Banfi S, Antonarakis SE, Minchiotti G, Cobellis G. Cardiomyogenesis is controlled by the miR-99a/let-7c cluster and epigenetic modifications. Stem Cell Res. 2014 Mar;12(2):323-37.
• Comes S, Gagliardi M, Laprano N, Fico A, Cimmino A, Palamidessi A, De Cesare D, De Falco S, Angelini C, Scita G, Patriarca EJ, Matarazzo MR, Minchiotti G. L-Proline Induces a Mesenchymal-like Invasive Program in Embryonic Stem Cells by Remodeling H3K9 and H3K36 Methylation. Stem Cell Reports. 2013 Oct 10;1(4):307-21.
• Franci G, Casalino L, Petraglia F, Miceli M, Menafra R, Radic B, Tarallo V, Vitale M, Scarfò M, Pocsfalvi G, Baldi A, Ambrosino C, Zambrano N, Patriarca E, De Falco S, Minchiotti G, Stunnenberg HG, Altucci L. The class I-specific HDAC inhibitor MS-275 modulates the differentiation potential of mouse embryonic stem cells. Biol Open. 2013 Aug 22;2(10):1070-7.
• D'Aniello C, Fiorenzano A, Iaconis S, Liguori GL, Andolfi G, Cobellis G, Fico A, Minchiotti G. The G-protein-coupled receptor APJ is expressed in the second heart field and regulates Cerberus-Baf60c axis in embryonic stem cell cardiomyogenesis. Cardiovasc Res. 2013 Oct 1;100(1):95-104.
• Guardiola O, Lafuste P, Brunelli S, Iaconis S, Touvier T, Mourikis P, De Bock K, Lonardo E, Andolfi G, Bouché A, Liguori GL, Shen MM, Tajbakhsh S, Cossu G, Carmeliet P, Minchiotti G. Cripto regulates skeletal muscle regeneration and modulates satellite cell determination by antagonizing myostatin. Proc Natl Acad Sci U S A. 2012 Nov 20;109(47):E3231-40.
• Casalino L, Comes S, Lambazzi G, De Stefano B, Filosa S, De Falco S, De Cesare D, Minchiotti G, Patriarca EJ. Control of embryonic stem cell metastability by L-proline catabolism. J Mol Cell Biol. 2011 Apr;3(2):108-22.
• Dentice M, Marsili A, Ambrosio R, Guardiola O, Sibilio A, Paik JH, Minchiotti G, DePinho RA, Fenzi G, Larsen PR, Salvatore D. The FoxO3/type 2 deiodinase pathway is required for normal mouse myogenesis and muscle regeneration. J Clin Invest. 2010 Nov;120(11):4021-30. doi: 10.1172/JCI43670.
• Lonardo E, Parish CL, Ponticelli S, Marasco D, Ribeiro D, Ruvo M, De Falco S, Arenas E, Minchiotti G. A small synthetic cripto blocking Peptide improves neural induction, dopaminergic differentiation, and functional integration of mouse embryonic stem cells in a rat model of Parkinson's disease. Stem Cells. 2010 Aug;28(8):1326-37.
• Lonardo E, Parish CL, Ponticelli S, Marasco D, Ribeiro D, Ruvo M, De Falco S, Arenas E, Minchiotti G. A small synthetic cripto blocking Peptide improves neural induction, dopaminergic differentiation, and functional integration of mouse embryonic stem cells in a rat model of Parkinson's disease. Stem Cells. 2010 Aug;28(8):1326-37.
• D'Aniello C, Lonardo E, Iaconis S, Guardiola O, Liguoro AM, Liguori GL, Autiero M, Carmeliet P, Minchiotti G. G protein-coupled receptor APJ and its ligand apelin act downstream of Cripto to specify embryonic stem cells toward the cardiac lineage through extracellular signal-regulated kinase/p70S6 kinase signaling pathway. Circ Res. 2009 Jul 31;105(3):231-8. doi: 10.1161/CIRCRESAHA.109.201186

• Prof. Dror Seliktar, Technion Faculty of Biomedical Engineering, Haifa, Israel;
• Prof. P. Carmeliet, Center for Transgene Technology and Gene Therapy, Belgium;
• Prof. S. Tajbakhsh, Pasteur Institute, Paris, France.  
• Prof. Henk Stunnenberg, Radboud Institute for Molecular Life Sciences, Nijmegen, Holland;
  
• Prof. G. Cossu, Stem Cell Research Institute, DIBIT, Milano, Italy;
• Prof. Lucia Altucci, Second University of Naples (SUN), Naples, Italy;
  
• Dott.ssa S. Brunelli, Stem Cell Research Institute, DIBIT, Milano, Italy;
• Dott.ssa A. Pegna-Zeuner, Istituto Superiore di Sanità (ISS), Rome, Italy;
  
• Dott. David Salomon, NIH, Bethesda, USA
• Prof. E. Arenas, Karolinska Institute, Stochkolm, Sweden;