12-4-1985- M.D. degree (summa cum laude) at the Medical School of Naples, University of Naples, Italy.

1985:"Visiting scientist", Laboratory of Molecular Biology, Section of Microbial Genetics. NIDDK, NIH, Bethesda Md. U.S.A.

1986 "Visiting scientist", Laboratory of Molecular Biology, Molecular, Cellular and Nutritional Endocrinology Branch, NIDDK, NIH Bethesda Md U.S.A.

1989-1998- C.N.R. Researcher, Centro di Endocrinologia ed Oncologia Sperimentale del C.N.R. Naples Italy

1989 "Visiting scientist", Department of Microbiology, Guy"s Hospital Medical School,, London, England.

1991- PhD in Cellular and Molecular Genetics

1993 "Visiting scientist", Laboratory of Molecular and Cellular Biology NCI, NIH.

from 1998 to 2004: Associate Professor at the Medical School of Catanzaro "Magna Graecia".

from 2004 to 2007: Associate Professor at the Medical School of Molise.

from 2007 to present: Associate Professor of General Pathology at the University of Naples Federico II, Faculty of Pharmacy.

We are currently studying the mechanisms involved in epigenetic changes (DNA methylation and chromatin modifications) in normal and tumor cells and tissues, following different stimuli. Our studies are focused on the role of DNA methylation, chromatin modification and methyl-binding proteins (MeCP2 and MBD2). These proteins represents a link between DNA methylation and chromatin configuration by interpreting the epigenetic signals. Recently, we have identified two human genes coding for two novel MBD2-interacting proteins (MBDin and TACC3) and two novel genes, RNF4 and PATZ, and demonstrated a potential role in human cancer. We are currently investigating the role of each of these proteins in epigenetic dynamics following different stimuli.
Ongoing projects
1) Epigenetic dynamics of retinoic acid and estrogen response either genome-wide and at gene-specific level. We have recently emonstrated a critical role of MeCP2 displacement and CpG-specific demethylation in neural cells for activation of methylated genes following retinoic acid treatment. Moreover, in collaboration with Prof. Avvedimento's group, we have evidences that DNA damage is accompanied by local hypermethylation leding to stable gene silencing even when a successful. DNA repair occurs.

2) DNA methylation and chromatin changes at gene-specific level and genome-wide in gastrointestinal cells co-cultured with Helicobacter pylori or treated with purified LPS. These studies are performed using high resolution technologies (MALDI, pyrosequencing).

3) Role of DNA methylation in neuropsychiatric disorders and deviant human behaviour. In a very recent study we found that BDNF promoter is frequently hypermethylated and partially silenced in brain Wernicke's area of suicide subjects compared to non-suicide control subjects irrespective of genome-wide methylation levels. The reported data reveal a novel link between epigenetic alteration in brain and suicidal behaviour. We are currently extend these studies to major psycosis and depressive disorders and verify the potential protective role of psycoactive drugs with proven activity of deacetylase inhibition including sodium valproate.

1) Keller S, Sarchiapone M, Ferraro A, Sacchetti, S, Carli V, Videtic A, Lembo F, Jovanovic N, Tomaiuolo R, Balazic J, Roy A, Fusco A, Bruni CB, Castaldo G and L. Chiariotti. Increased BDNF promoter methylation in Wernicke's area of suicide subjects. Arch. Gen. Psychiatry 2010. In Press

2) Angrisano T, Sacchetti S, Natale F, Cerrato A, Pero R, Keller S, Peluso S, Perillo B, Avvedimento VE, Fusco A, Bruni CB, Lembo F, Santoro M, and Chiariotti L. Chromatin and DNA methylation dynamics during retinoic acid-induced RET gene transcriptional activation in neuroblastoma cells.
Nucleic Acids Res. 2011 Mar 1;39(6):1993-2006. Epub 2010 Oct 15.

3) Pero R, Peluso S, Angrisano T, Tuccillo C, Sacchetti S, Keller S, Tomaiuolo R, Bruni CB, Lembo F, and Chiariotti L. Chromatin and DNA methylation dynamics of Helicobacter pylori-induced COX-2 activation
Int J Med Microbiol. 2011 Feb;301(2):140-9. Epub 2010 Oct 8.

4) Angrisano T, Pero R, Peluso S, Keller S, Sacchetti S, Bruni CB, Chiariotti L, Lembo F.
LPS-induced IL-8 activation in human intestinal epithelial cells is accompanied by specific histone H3 acetylation and methylation changes.
BMC Microbiol. 2010 Jun 14;10:172.

5) Natale F, Angrisano T, Lembo F, Pero R, Keller S, Sacchetti S, Fusco A, Avvedimento VE, Bruni CB and L. Chiariotti. Epigenetic dynamics of RA-induced RET activation in neuroblastoma cells. Nucleic Acids Res. (2009) u.r.

6) Castaldo I, Pinelli M, Monticelli A, Acquaviva F, Giacchetti M, Filla A, Sacchetti S, Keller S, Avvedimento VE, Chiariotti L, Cocozza S. DNA methylation in intron 1 of the frataxin gene is related to GAA repeat length and age of onset in Friedreich ataxia patients. J Med Genet. 2008 Dec;45(12):808-12. Epub 2008 Aug 12.

7) Martinez Hoyos J, Ferraro A, Sacchetti S, Keller S, De Martino I, Borbone E, Pallante P, Fedele M, Montanaro D, Esposito F, Cserjesi P, Chiariotti L, and Fusco A. HAND1 gene expression is negatively regulated by the High Mobility Group A1 proteins and is drastically reduced in human thyroid carcinomas. Oncogene. 2009 Feb 12;28(6):876-85. Epub 2008 Dec 8.

8) Zarrilli F, Angiolillo A, Castaldo G, Chiariotti L, Keller S, Sacchetti S, Marusic A, Zagar T, Carli V, Roy A, Sarchiapone M. Brain derived neurotrophic factor (BDNF) genetic polymorphism (Val66Met) in suicide: a study of 512 cases. Am J Med Genet B Neuropsychiatr Genet. 2009 Jun 5;150B(4):599-600.

9) Perillo B, Ombra MN, Cuozzo C, Sacchetti S, Sasso AR, Bertoni A, Chiariotti L, Abbondanza C, and Avvedimento EV. DNA oxidation, triggered by demethylation of H3K9me2, is essential for estrogen-induced transcription. Science 319:202-206 (2008).
10) Fedele M, R Franco, G Salvatore, MP Paronetto, F Barbagallo, GM Pierantoni, L Chiariotti L, C. Sette, D Tramontano, A Fusco and P Chieffi. PATZ Gene has a Critical Role in Spermatogenesis and Testicular Tumors. J. Pathol. 215:39-47 (2008)

11) Cuozzo C, Porcellini A, Angrisano T, Morano A, Lee B, Pardo AD, Messina S, Iuliano R, Fusco A, Santillo MR, Muller MT, L. Chiariotti L, Gottesman ME, Avvedimento EV. DNA Damage, Homology-Directed Repair, and DNA Methylation. PLoS Genet. 2007 (Pub) 3(7):e110

12) Angrisano T, Lembo F, Pero R, Natale F, Fusco A, Avvedimento VE, Bruni CB, and L. Chiariotti. TACC3 mediates the association of MBD2 with histone acetyltransferases and relieves transcriptional repression of methylated promoters. Nucleic Acids Res. 34:364-372 (2006).

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