1.Biochemical, molecular and epigenetic mechanisms underlying rare genetic neurodevelopmental disorders in in vitro models of brain cells derived from human induced Pluripotent Stem cells (iPScells):
a.AGC1-deficiency: funded by the Telethon Foundation, in collaboration with Dr. Massimo Lasorsa, University of Bari, and with Prof. Laura Mercolini and Dr. Federico Giorgi, FaBiT;
b. Angelman syndrome: in collaboration with FAST Italia Foundation and Prof. Cristina Alberini, NYU (USA);
2. Role of microglia and in particular of miRNAs released via microglial exosomes in the pathophysiology of the CNS: in collaboration with Dr. Giampaolo Zuccheri, FaBiT;
3. Study of the epigenetic mechanisms of regulation of circadian rhythm genes in Neural Stem Cells (NSCs) from iPS cells in Alzheimer's disease: within the MSCA-JDN Tclock4AD project coordinated by Prof. Maria Laura Bolognesi, FaBiT;
4. Screening and study of the effect of small synthetic molecules on neuronal survival/death and glial activation: in collaboration with Prof. Maria Laura Bolognesi and Prof. Anna Minarini, FaBiT.
1a. Biochemical, molecular and epigenetic mechanisms underlying rare genetic neurodevelopmental disorders in in vitro models of brain cells derived from human induced Pluripotent Stem cells (iPScells): AGC1-deficiency. As part of the project financed by the Telethon Foundation, in collaboration with Dr. Massimo Lasorsa, University of Bari, and with Prof. Laura Mercolini and Dr. Federico Giorgi, FaBiT, by using in vitro models of brain cells derived from human iPS, both precursors of oligodendrocytes and neurons, we are studying the mechanisms of biochemical-metabolic signaling and regulation of gene expression in physiological conditions and their alterations in pathological conditions in AGC-1 deficiency, an ultra-rare genetic disease caused by a defect in the gene that codes for the mitochondrial transporter AGC1, which causes myelin degeneration and neuronal death with very serious neurological effects in order to identify new potential therapeutic targets.
1b. Biochemical, molecular and epigenetic mechanisms underlying rare genetic neurodevelopmental disorders in in vitro models of brain cells derived from human induced Pluripotent Stem cells (iPScells): Angelman syndrome. In the framework of the PNRR-PE12 Mnesys, Spoke 1-Neurodevelopment project, in collaboration with FAST Italia association (Foundation for Angelman Syndrome Therapeutics) and with Prof. Cristina Alberini of NYU (USA), we started a project to study of neuronal molecular alterations in Angelman syndrome, a rare genetic neurodevelopmental disease, by using neurons derived from iPS cells of patients and related healthy controls from the FAST Italia biobank, in order to evaluate the potential effect of the activation of the IGF2 receptor.
2. Role of microglia and in particular of miRNAs released via microglial exosomes in the pathophysiology of the CNS: in the framework of the PNRR-CN3 project "Development of gene therapy and drugs based on RNA technology", Spoke 1 "Neuroinflammation", in collaboration with Dr. Giampaolo Zuccheri, FaBiT. By using in vitro models of microglia, we have focused on the release of proteins and especially miRNAs through exosomes, to understand their role in neuroinflammation spreading and we are testing immunomodulation strategies through nucleic acid nanostructures able to regulate specific exosomal miRNAs.
3. Study of the epigenetic mechanisms of regulation of circadian rhythm genes in NSCs from iPS cells in Alzheimer's disease: within the MSCA-JDN Tclock4AD project coordinated by Prof. Maria Laura Bolognesi, FaBiT, we aim to study the expression regulation of circadian rhythm genes through histone acetylation in neural stem cells derived from iPS of Alzheimer's patients and healthy controls in order to identify new potential therapeutic targets.
4. Screening and study of the effect of small synthetic molecules on neuronal survival/death and glial activation: in collaboration with prof. Maria Laura Bolognesi and with Prof. Anna Minarini, FaBiT, we are carrying out the screening and the functional study of the effect of small synthetic molecules on neuronal survival and/or death and on glial activation, with particular reference to the phenotypic shift (M2 vs. M1) of microglia.
