Stressful events induce   activation of the autonomic nervous system and the Hypotalamus-Pituitary-Adrenal (HPA) axis, with consequent increase in glucocorticoid (GC) synthesis and release.
The ubiquitous expression of GC receptors and the multitude of functions of GCs confer this system an essential role in the response to stress and restoration of homeostasis. These stress-induced changes are largely mediated by modifications in gene expression and protein synthesis.
Precise regulation of the HPA axis activity is very important for the organism; indeed, chronic exposure to GCs results in various adverse side effects, such as osteoporosis, diabetes, hypertension and neurodegeneration.
Goal of my research project is to uncover the genetic, epigenetic effect that GCs exert in brain regions particularly susceptible to stressful stimuli as hippocampus, with particular attention to gene expression modulation of the GC receptor (Gr), his target genes and non coding RNAs.
My interest has also been addressed in the study of those diseases in which there are an altered glucocorticoids levels due to  the high degree of  inflammation such as Duchennne muscular dystrophy(DMD). The DMD is an X-linked muscle disease caused by mutations in the DMD gene that code for dystrophin. This protein has an important structural role during muscle contraction. Fragile muscle fiber and instable sarcolemma are some of the outcomes of the protein mutation. These alterations lead to chronic inflammation, which is an important feature of the disease pathophysiology. The patients also exhibit significant developmental cognitive and behavioral abnormalities, including increased frequency of autism and attention deficit disorders.
The study will be performed both in vitro (neuron cultures and neuroblastoma cell lines administered with GC,) and in vivo (GC injection) in mdx (a DMD animal model) and wild-type mice by administration of glucocorticoid hormones  (Dexamethasone and Cortisone).

1) Ruberti I.,  Fragapane P.,  Pierandrei-Amaldi P.,  Beccari E., Amaldi  F.  and Bozzoni I.  -(1982)- Characterization of  Histone genes isolated from Xenopus laevis and Xenopus tropicalis genomic libraries - Nucleic Acid Res., 10  p.7543-7559

2)  Bozzoni I.,  Fragapane P.,  Annesi F.,  Pierandrei-Amaldi P., Amaldi  F.  and Beccari E.,  -(1984)- Expression of two  X.laevis ribosomal  protein  genes in injected frog  oocytes.  A  specific splicing block interferes with the L1 maturation - J. Mol. Biol., 180  p.987- 1005

 3)  Caffarelli E.,  Fragapane P.,  Gehring C.  and Bozzoni  I.  -(1987)- The accumulation of mature RNA for the X.laevis ribosomal protein L1 is controlled at the level of splicing and turnover of the precursor RNA-  EMBO Journal 6  p.3493-3498

 4) Fragapane P.,  Caffarelli E., Santoro B., Sperandio S., Lener M.  and Bozzoni I.  (1990) - Splicing control of the L1 ribosomal protein   gene  of  X.laevis:   structural  similarities  between sequences  present  in  the  regulatory intron  and  in  the  28S ribosomal RNA -

Molecular Biology Reports 14  p. 111-112

 5) Fragapane P., Caffarelli E., Lener M., Prislei S., Santoro B. and Bozzoni I. (1992)- Identification of the sequences responsible for the in vivo  splicing phenotype of the regulatory intron of the L1ribosomal protein gene of Xenopus laevis. - Mol . and Cell. Biology 12  p.1117- 1125.

6) Fragapane P., Prislei S., Michienzi A., Caffarelli E. and Bozzoni I. (1993)- A novel small nucleolar RNA  (U16) is encoded inside a ribosomal protein intron and originates by processing of the pre-mRNA- EMBO Journal 12  p.2921-2928

 7) Prislei S., Michienzi A., Presutti C., Fragapane P. and Bozzoni I. (1993)- Two different snoRNAs are encoded in introns of amphibian and human L1 ribosomal protein genes- Nucleic Acid Res. 21  p.5824-5830

 8) Caffarelli E., Fatica A., Prislei S., De Gregorio E., Fragapane P. and Bozzoni I. (1996)- Processing of the intron-encoded U16 and U18 snoRNAs: the conserved C and D boxes control both the processing reaction and the stability of the mature snoRNA.- EMBO Journal 15  p.1121-1131

 9)Atzorn V.,Fragapane P. and Kiss T.(2004) U17/snR30 is a ubiquitous snoRNA with two conserved sequence motifs essential for 18S rRNA production- Mol. and Cell.Biology 24 p.1769-1778

 10)Rinaldi A.,, Vincenti S., De Vito F., Bozzoni I., Oliverio A., Presutti C., Fragapane P. and Mele A. (2010) Stress induces region specific alterations in micro RNA expression in mice Behav Brain Res.;208(1):265-9. Epub 2009 Nov 11.

11)Learning induced epigenetic modifications in the ventral striatum are necessary for long-term memory (2014) GaglioD , Capitano F, Mastrodonato A, Minicocci E, Deiana C, Fragapane P, Camilloni G, Mele A Behavioural brain research 265, 61-68

12) microRNAs modulate spatial memory in the hippocampus and in the ventral striatum in a region-specific manner(2016)F Capitano, J Camon, V Ferretti, V Licursi, F De Vito, Arianna Rinaldi, S Vincenti, C Mannironi, P     Fragapane, Irene Bozzoni, A Oliverio, R Negri, C Presutti, A. Mele Molecular neurobiology, 53 (7), 4618-4630

Education

1976B.A in Classical studies

1984 Degree in Biology (summa cum laude): University of Rome ”La Sapienza” Final dissertation “Involvement of small nuclear RNAs in the splicing of the r-protein L1 mRNA of X.laevis   by  oocytes  microinjection”.

2000Official equalization from CNR istitution

between research experience and PhD level 

Research Experiences

1980-1984Centro Acidi Nucleici of C.N.R.Rome

 Experimental  thesis in the laboratory of Prof. Irene Bozzoni

1984EMBL (Heidelberg)

Laboratory of Prof. Gianni Cesareni 

1984 -1990Centro Acidi Nucleici  C.N.R. 

Research fellowship awarded by C.N.R.

1990Centro Acidi Nucleici

Permanent position as Collaborator of Research Agency 

2001 Istituto di Biologia e Patologia molecolari 

permanent position as researcher

Post-doctoral training

1997-1998EMBO short-term fellowship 

Laboratory of Dr. Tamas Kiss

LBME-Toulouse-France

1998NATO-CNR senior fellowship

Laboratory of Dr. Tamas Kiss

LBME-Toulouse-France

1999-2000 Poste-rouge as assistant researcher at

LBME Toulouse -France