CELLULAR AND MOLECULAR STUDIES OF SYNAPTIC PLASTICITY AND CANCER IN THE CONTEXT OF INTELLECTUAL DISABILITIES
Memory formation and cognitive processes that rely on activity-dependent synaptic plasticity are affected by local protein synthesis and shaping of the synapses. Synaptic inputs dictate the time, place and amount of protein synthesis necessary for the single synapses. Dysregulation of these mechanisms leads to spine dysmorphogenesis and to a variety of neuropathological conditions including the most common form of inherited mental retardation, the Fragile X syndrome (FXS), which is due to the absence or mutation of a single protein, FMRP. FMRP is involved in multiple steps of neuronal messenger RNA metabolism such as transport, stability and local.
Our work, as well as the work of others, has shown that Autistic Spectrum Disorder (ASD), Schizophrenia (SCZ) as well as Alzheimer’s Disease (AD) are linked to FMRP function.
We aim at identifying molecular pathways that are impaired in FXS and other disabilities such as ASD and SCZ using mouse and fly models as well as cell lines from patients. One of our major goals is to understand the regulation of synaptic protein synthesis and actin remodeling during brain development in physiological and the above-mentioned pathological conditions. We believe that the knowledge we acquire examining molecular mechanisms at the synapses will offer a major inroad into the understanding of processes that govern not only learning and memory, but also human behavior and neurodegenerative diseases that arise from malfunctioning synapses “synaptopathies”.
We aim, with the use of different mouse and fly models, stem cells and in collaboration with clinical researchers, to develop possible pharmacological approaches to modulate some aspects of FXS, ASD and SCZ.
A few clinical reports showed a decreased risk of cancer and neuroprotection in individuals with Fragile X. We have recently showed that FMRP levels correlate with prognostic indicators of aggressive breast cancer and metastasis. We have also identified key molecules involved in epithelial to mesenchymal transition and metastases formation, which are targeted at the mRNA level by FMRP.
We are currently working on the molecular mechanisms conserved between cancer progression and neuronal development and exploring the possibility to identify potential therapeutic targets hindering metastasis dissemination.
The Fragile X Protein binds mRNAs involved in cancer progression and modulates metastasis formationLucá R, Averna M, Zalfa F, Vecchi M, Bianchi F, Fata G, Del Nonno F, Nardacci R, Bianchi M, Nuciforo P, Munck S, Parrella P, Moura R, Signori E, Alston R, Kuchnio A, Farace M, Fazio V, Piacentini M, De Strooper B, Achsel T, Neri G, Neven P, Evans D, Carmeliet P, Mazzone M, Bagni CEMBO Molecular Medicine, 5, 1523-1536, 2013 The fragile X syndrome protein represses activity-dependent translation through CYFIP1, a new 4E-BPNapoli I, Mercaldo V, Boyl P, Eleuteri B, Zalfa F, De Rubeis S, Di Marino D, Mohr E, Massimi M, Falconi M, Witke W, Costa-Mattioli M, Sonenberg N, Achsel T, Bagni CCELL, 134, 1042-54, 2008 A new function for the fragile X mental retardation protein in regulation of PSD-95 mRNA stabilityZalfa F, Eleuteri B, Dickson K, Mercaldo V, De Rubeis S, Di Penta A, Tabolacci E, Chiurazzi P, Neri G, Grant S, Bagni CNATURE NEUROSCIENCE, 10, 578-87, 2007 The fragile X syndrome protein FMRP associates with BC1 RNA and regulates the translation of specific mRNAs at synapsesZalfa F, Giorgi M, Primerano B, Moro A, Di Penta A, Reis S, Oostra B, Bagni CCELL, 112, 317-27, 2003
18/09/2013 - Several psychiatric conditions share the same brain cell abnormalities. Claudia Bagni and her group have unraveled how a single protein orchestrates two biological processes to form proper contacts between brain cells.
18/09/2013 - Claudia Bagni (VIB/KU Leuven, Belgium, and the University of Rome Tor Vergata, Italy), has identified the way Fragile X Mental Retardation Protein or FMRP contributes to the progression of breast cancer.
05/06/2013 - This meeting provides a unique opportunity to bring together researchers with common interests in RNA transport, localization and localized translation in a wide range of experimental systems.
05/06/2013 - The IBRO-Kemali College on “RNA and the Etiology of Brain Disease” will be held at the Neuroscience School of Advanced Studies from August 25th until August 31st, 2013.
PhD: University of Rome, Italy, 1992
Postdoc: CNRS, France, 1991-93
Postdoc: Harvard University, Cambridge, USA, 1993-94
Postdoc: EMBL, Germany, '94-'96
Professor, University of Rome ”Tor Vergata”, Italy, since 2002
EMBO member since 2011
VIB Group leader since 2008