Antonella Riccio Research Group

1996 MD, PhD Catholic University School of Medicine Rome, Italy
Antonella Riccio
Tel: 020 7679 7814
Fax: 020 7679 7805
Awards: 
2001 Young Investigator Barry Woods Award for Excellnce in Science Johns Hopkins University Baltimore USA
2001-2004 Armenise-Harvard Foundation Career Development Award
2005-2009 MRC Career Development Award
2009-present MRC Senior Non-Clinical Fellowship
2013 Elected UCL Academic Role Model
2014 Wellcome Trust Senior Investigator Award
Previous Posts: 
1997-2002 Postdoctoral Fellow Johns Hopkins University Baltimore USA
2002-2004 Research Associate Johns Hopkins University Baltimore USA

The proper wiring of the mammalian nervous system is a task of unique complexity, which requires specific point-to-point connections between billions of neurons. At the heart of this fundamental biological process lies the ability of extracellular cues, such as neurotrophins, to regulate the expression of specific genes that encode proteins that promote neuronal survival, axon growth, differentiation, synapse formation, and, later, synaptic plasticity. Two major regulatory events influence gene expression: binding and activation of nuclear proteins to cis-acting regulatory elements in gene promoters and epigenetic modifications that alter chromatin packing and thereby access of DNA-binding proteins to their DNA sites. While much work has been published on how neurotrophins and other extracellular signals regulate the nuclear factors that control gene expression during neuronal development, surprisingly little is known about the mechanisms by which extracellular cues induce chromatin modifications in these cells. Interestingly, several chromatin-modifying proteins have been associated with neurodegenerative diseases and mental retardation syndromes. Understanding how neurotrophins and neurotransmitters induce chromatin remodelling is therefore, of great importance and may provide the rationale for novel treatment strategies.

Riccio fig 1_1.jpg

Fig 1: DAF staining of cortical neurons treated with BDNF. Nitric oxide accumulates in both the cytoplasm and the nucleus

Once a gene is transcribed, its mRNA must be translated into a protein, which then has to be transported to where it is needed. This transport can be especially challenging in differentiated neurons because the nucleus can be very far away from the final location of the protein: the growth cone of a sensory neuron in a mouse embryo, for example, can be millimetres, or even centimetres away from the cell body. Moreover, the half-life of a newly translated protein is often much shorter than the time required for it to travel along the axon to the growth cone. Therefore, many mRNAs encoding proteins required for either axon growth during development or axonal regeneration after injury must be transported and locally translated in axons. The targeting and translation of many of these RNAs may well be regulated by neurotrophins. Thus, the identification of axonal mRNAs and the signaling pathways that regulate their local translation should help us understand how neurotrophins promote axon growth during development and facilitate nerve regeneration in adults.

In our laboratory, we are currently following three lines of research:

 

1) Nitric oxide-dependent regulation of gene expression and chromatin remodelling in developing neurons

 

Riccio fig 2_1.jpg

Fig 2: CHD3 immunostaining of mouse cortex at the indicated developmental stages.

 

We have recently identified nitric oxide (NO) as a novel mediator of gene expression in neurons. We have already characterized histone deacetylase 2 (HDAC2) as a target of BDNF-dependent nuclear S-nitrosylation. We are now performing mass spectrometry analysis of nuclear proteins that co-immunoprecipitate with HDAC2. We are also exploring whether S-nitrosylation of HDAC2 influences the expression of genes necessary for neurogenesis and neuronal migration in vivo.

2) Analysis of nuclear architecture and chromatin structure following synaptic activation in vivo and in vitro

 

Riccio fig 3_1.jpg

Fig 3: DNA FISH showing colocalization of c-fos with RNA POLII transcriptional factories

 

A second research theme in my laboratory is centred on the identification of neuronal genes that are regulated in vivo following exposure to Novel Enriched Environmental (NEE) conditions, a complex somatosensory mode of stimulation.. Prolonged exposure to NEE protects against neurodegeneration; it also enhances neurogenesis, dendritic arborization and resistance to apoptosis. We initially identify genes regulated following NEE conditions, by using ChIPSeq assay, a technique that combines chromatin immunoprecipitation with large-scale direct ultrahigh-throughput DNA sequencing. Analysis of H3K9/K14 acetylation (a chromatin mark enriched in promoter regions of actively transcribed genes) of somatosensory cortex coupled with microarray analysis revealed that following exposure to NEE conditions neurons undergo a reactivation of a developmental transcriptional program. Moreover, an iperacetylated and highly conserved region was significantly enriched within the promoters of genes induced following NEE stimulation. We have now evidence that this sequence mediates chromatin tethering and recruitment to transcription factories of genes that are co-transcribed following synaptic stimulation.

3) Transport and targeting of mRNAs to axons of developing neurons

Riccio fig 5_1.jpg

Fig 5: Compartmentalized cultures of sympathetic neurons

To identify transcripts localized in axons we have performed an unbiased screen by combining compartmentalized cultures of sympathetic neurons with Sequential Analysis of Gene Expression. More than 11,000 tags matching known transcripts were found in axons. Surprisingly, the most abundant transcript in axons IMPA1, a key enzyme that regulates the inositol cycle and the main target of lithium in neurons. We also found that a novel localization element within the 3’UTR of IMPA1 specifically targeted IMPA1 transcript to sympathetic neuron axons and regulated local IMPA1 translation in response to Nerve Growth Factor (NGF). We are now performing extensive 5’ and 3’ RACE analyses of transcripts that are enriched in axons with the scope of identifying common structural features within the 3’ and 5’UTRs that will allow the biochemical purification of mRNA binding proteins. We are also testing the hypothesis that neurotrophins induce cytoplasmic remodelling of 3’UTR regions that is required for translational de-repression of axonal transcripts.

Lab Members: 
Catia Andreassi
Luca Crepaldi
Aniko Ludanyi
Justyna Nitarska
Cristina Policarpi
Publications
Jump to: 2013 | 2012 | 2010 | 2009 | 2008 | 2006 | 2003 | 2002 | 2001 | 2000 | 1999 | 1998 | 1997 | 1996
Number of items: 25.

2013

Burton, A; Azevedo, C; Andreassi, C; Riccio, A; Saiardi, A; (2013) Inositol pyrophosphates regulate JMJD2C-dependent histone demethylation. PNAS , 110 (47) 18970 - 18975. 10.1073/pnas.1309699110.

Loss, O; Wu, CT; Riccio, A; Saiardi, A; (2013) Modulation of inositol polyphosphates levels regulates neuronal differentiation. Mol Biol Cell 10.1091/mbc.E13-04-0198.

Nott, A; Nitarska, J; Veenvliet, JV; Schacke, S; Derijck, AA; Sirko, P; ... Riccio, A; + view all (2013) S-nitrosylation of HDAC2 regulates the expression of the chromatin-remodeling factor Brm during radial neuron migration. Proc Natl Acad Sci U S A , 110 (8) 3113 - 3118. 10.1073/pnas.1218126110.

2012

Fusco, S; Ripoli, C; Podda, MV; Ranieri, SC; Leone, L; Toiletta, G; ... Pani, G; + view all (2012) A role for neuronal cAMP Responsive Element Binding (CREB)-1 in brain responses to calorie restriction. Proceedings of the National Academy of Sciences , 109 (2) 621 - 626.

Marine, S; Freeman, J; Riccio, A; Axenborg, ML; Pihl, J; Ketteler, R; Aspengren, S; (2012) High-throughput transfection of differentiated primary neurons from rat forebrain. J Biomol Screen , 17 (5) 692 - 696. 10.1177/1087057112439233.

Nott, A; Nitarska, J; Veenvliet, J; Schacke, S; Derijck, A; Murchardt, J; ... Riccio, A; + view all (2012) S-nitrosylation of histone deacetylase 2 regulates the expression of the ATP-dependent chromatin remodeling factor Brm during radial neuron migration. PNAS

2010

Andreassi, C; Zimmermann, C; Mitter, R; Fusco, S; Devita, S; Saiardi, A; Riccio, A; (2010) An NGF-responsive element targets myo-inositol monophosphatase-1 mRNA to sympathetic neuron axons. NAT NEUROSCI , 13 (3) 291 - U6. 10.1038/nn.2486.

Riccio, A; (2010) Dynamic epigenetic regulation in neurons: enzymes, stimuli and signaling pathways. Nature Neuroscience , 13 (11) 1330 - 1337.

Riccio, A; (2010) New endogenous regulators of ClassI histone deacetylases. Science Signaling , 3 (103) 1 - 4.

2009

Andreassi, C; Riccio, A; (2009) To localize or not to localize: mRNA fate is in 3 ' UTR ends. TRENDS CELL BIOL , 19 (9) 465 - 474. 10.1016/j.tcb.2009.06.001.

Crepaldi, L; Riccio, A; (2009) Chromatin learns to behave. EPIGENETICS , 4 (1) 23 - 26.

Nott, A; Riccio, A; (2009) Nitric oxide-mediated epigenetic mechanisms in developing neurons. Cell Cycle , 1 (8) 725 - 730.

Watson, PM; Riccio, A; (2009) Nitric oxide and histone deacetylases: A new relationship between old molecules. Commun Integr Biol , 2 (1) 11 - 13.

2008

Nott, A; Watson, PM; Robinson, JD; Crepaldi, L; Riccio, A; (2008) S-nitrosylation of histone deacetylase 2 induces chromatin remodelling in neurons. NATURE , 455 (7211) 411 - U67. 10.1038/nature07238.

2006

Riccio, A; Alvania, RS; Lonze, BE; Ramanan, N; Kim, T; Huang, YF; ... Ginty, DD; + view all (2006) A nitric oxide signaling pathway controls CREB-mediated gene expression in neurons. MOL CELL , 21 (2) 283 - 294. 10.1016/j.molcel.2005.12.006.

2003

Bedogni, B; Pani, G; Colavitti, R; Riccio,; A,; Borrello, S; ... Galeotti, T; + view all (2003) Redox regulation of cAMP-responsive element-binding protein and induction of manganous superoxide dismutase in nerve growth factor-dependent cell survival. Journal of Biological Chemistry , 278 (19) 16510 - 16519. 10.1074/jbc.M301089200. Gold open access

2002

Lonze, BE; Riccio, A; Cohen, S; Ginty, DD; (2002) Apoptosis, axonal growth defects and degeneration of peripheral neurons in mice lacking CREB. Neuron , 34 371 - 385. 10.1016/S0896-6273(02)00686-4.

Riccio, A; Ginty, DD; (2002) What a privilege to reside at the synapse: NMDA receptor signaling to CREB. Nature Neuroscience , 5 389 - 390. 10.1038/nn0502-389.

2001

Andreassi, C; Zoli, A; Riccio, A; Scuderi, F; Lobardi, L; Altomonte, L; Eboli, ML; (2001) Anticardiolipin antibodies in patients with primary antiphospholipid syndrome: a correlation between IgG titre and antibody-induced cell dysfunctions in neuronal cell cultures. Clinical Rheumatology , 20 (5) 314 - 318.

2000

Ahn, S; Riccio, A; Ginty, DD; (2000) Spatial consideration for stimulus-dependent transcription in neurons. Annual Reviews of Phisyology , 62 803 - 823.

1999

Riccio, A; Ahn, S; Davenport, CM; Blendy, JA; Ginty, DD; (1999) Mediation by a CREB family transcription factor of NGF-dependent survival of sympathetic neurons. Science , 286 2358 - 2361.

1998

Qian, X; Riccio, A; Zhang, Y; Ginty, DD; (1998) Identification and characterization of novel substrates of Trk receptors in developing neurons. Neuron , 21 1017 - 1029.

Riccio, A; Andreassi, A; Eboli, ML; (1998) Antiphospholipid antibodies bind to rat cerebellar granule cells: the role of NMDA receptors. Neuroscience Letters , 258 1 - 3.

1997

Riccio, A; Pierchala, BA; Ciarallo, CL; Ginty, DD; (1997) An NGF-TrkA-mediated retrograde signal to transcription factor CREB in sympathetic neurons. Science , 277 1097 - 1100.

1996

Riccio, A; Esposito, E; Eboli, ML; (1996) Modulation by protein kinase C of nitric oxide and cyclic GMP poffation in cultured cerebellar granule cells. Brain Research , 718 (1-2) 159 - 164.

This list was generated on Fri Sep 19 23:04:06 2014 BST.