Catalogo dei Corsi di studio

Di Angelantonio Silvia
Associate Professor of Physiology Sapienza University of Rome

A. Bibliometric data

Peer reviewed publications: 63 (Pubmed)
H index: 25 (Scopus)
Citations: 1619 (Scopus)
Total IF: 320.5 (WOS)

B. Positions and Honors

2002-2002 Postdoctoral fellow. SISSA, Trieste, Italy.
2002-2003 Postdoctoral fellow. Fondazione Santa Lucia, Roma, Italy.
2003-2006 Postdoctoral fellow. Sapienza University, Roma, Italy.
2005-2006 Reasearch fellow. Neuromed Institute, Pozzilli, Italy.
2006-2007 Reasearch fellow C.O.N.I. Science and Sport Medicine Institute, Roma, Italy.
2006-2008 Research assistant in Physiology. Sapienza University, Roma Italy.
2015-present Affiliated researcher Istituto Italiano di Tecnologia, Center for Life Nano Science
2018-present Scientific advisor CrestOptics SPA - D-tails srl
2019-present Associate Professor of Physiology, Department of Physiology and Pharmacology, Sapienza University, Rome.

Honors and Awards:
2003 Young research award . National meeting of Italian league against epilepsy (LICE).
2008 Selected speaker award 5th Meeting of Molecular Mechanism in Neuroscience.
2017 Equal Opportunities Award PNICube 2017
2017 Equal Opportunity Award StartCup Lazio 2017
2017 StartCup Lazio 2017 (1st Classified)
2018 Best Presentation Award in Biotechnology National Roadshow BioInItaly Lazio Innova 2017
2018 National Scientific Qualification for Full Professor of Physiology

C. Contributions to Science

1. Functional properties and modulation of neuronal nicotinic receptors (nAChRs) in homeostasis and disease. As a PhD student, and as a Pot Doc, using patch clamp and confocal calcium imaging, I studied the expression and the functional properties of nAChRs in native cells and in heterologous expression systems [12 papers]. I developed a novel class of CGRP-derived peptides with facilitating action on nAChRs (Eur. patent app. N° PCT/IT01/00477). These studies allowed to correlate basal mechanisms of excitatory cholinergic transmission with clinical aspects in amyotrophic lateral sclerosis [4 papers] and Duchenne s muscular dystrophy (DMD) [2 papers].

a) Giniatullin R, Di Angelantonio S, Marchetti C, Sokolova E, Khiroug L, Nistri A. Calcitonin gene-related peptide rapidly downregulates nicotinic receptor function and slowly raises intracellular Ca2+ in rat chromaffin cells in vitro. J Neurosci. 1999
b) Di Angelantonio S, Bernardi G, Mercuri NB. Donepezil modulates nicotinic receptors of substantia nigra dopaminergic neurones. Br J Pharmacol. 2004
c) Di Angelantonio S, De Stefano ME, Piccioni A, Lombardi L, Gotti C, Paggi P. Lack of dystrophin functionally affects 3 2/ 4-nicotinic acethylcholine receptors in sympathetic neurons of dystrophic mdx mice. Neurobiol Dis. 2011
d) Di Angelantonio S, Piccioni A, Moriconi C, Trettel F, Cristalli G, Grassi F, Limatola C. Adenosine A2A receptor induces protein kinase A-dependent functional modulation of human (alpha)3(beta)4 nicotinic receptor. J Physiol. 2011

2. Functional properties of GABA receptors in homeostasis and disease. Then, during my second Post Doc I moved to the study of GABAA receptors, characterizing functional properties of GABAA receptors in human temporal lobe epilepsy. I developed an innovative approach to record single neuron and glial cells in slices from surgically resected human cerebral tissue [4 papers]. I also studied the mechanism of tumor associated epilepsy, demonstrating that glutamate, released by glioma cells, depolarizes neuronal Cl- equilibrium causing GABA mediated hyperexcitability [2 papers].

a) Palma E, Ragozzino DA, Di Angelantonio S, Spinelli G, Trettel F, Martinez-Torres A, Torchia G, Arcella A, Di Gennaro G, Quarato PP, Esposito V, Cantore G, Miledi R, Eusebi F. Phosphatase inhibitors remove the run-down of gamma-aminobutyric acid type A receptors in the human epileptic brain. Proc Natl Acad Sci U S A. 2004
b) Ragozzino D, Palma E, Di Angelantonio S, Amici M, Mascia A, Arcella A, Giangaspero F, Cantore G, Di Gennaro G, Manfredi M, Esposito V, Quarato PP, Miledi R, Eusebi F. Rundown of GABA type A receptors is a dysfunction associated with human drug-resistant mesial temporal lobe epilepsy. Proc Natl Acad Sci U S A. 2005
c) Di Angelantonio S, Murana E, Cocco S, Scala F, Bertollini C, Molinari MG, Lauro C, Bregestovski P, Limatola C, Ragozzino D. A role for intracellular zinc in glioma alteration of neuronal chloride equilibrium. Cell Death Dis. 2014

3. Functional role of microglia/neuron interaction in physiological and pathological conditions. As a researcher I focused on the impact of neuroinflammation in brain pathologies with major interest on the role played by microglia cells on neuron/microglial crosstalk with multidisciplinary approaches [9 papers]. I focused on the morphological and functional characterization of microglia cells in physiological and pathological conditions looking at the ability of microglia cells of monitoring tissue homeostasis and rearranging processes towards an injury [3 papers].

a) Ragozzino D, Di Angelantonio S, Trettel F, Bertollini C, Maggi L, Gross C, Charo IF, Limatola C, Eusebi F. Chemokine fractalkine/CX3CL1 negatively modulates active glutamatergic synapses in rat hippocampal neurons. J Neurosci. 2006
b) Di Angelantonio S, Bertollini C, Piccinin S, Rosito M, Trettel F, Pagani F, Limatola C, Ragozzino D. Basal adenosine modulates the functional properties of AMPA receptors in mouse hippocampal neurons through the activation of A1R A2AR and A3R. Front Cell Neurosci. 2015
c) Basilico B, Pagani F, Grimaldi A, Cortese B, Di Angelantonio S, Weinhard L, Gross C, Limatola C, Maggi L, Ragozzino D. Microglia shape presynaptic properties at developing glutamatergic synapses. Glia. 2019
d) Pagani F, Testi C, Grimaldi A, Corsi G, Cortese B, Basilico B, Baiocco P, De Panfilis S, Ragozzino D, Di Angelantonio S. Dimethyl Fumarate Reduces Microglia Functional Response to Tissue Damage and Favors Brain Iron Homeostasis. Neuroscience. 2019

4. Identification of neurodegenerative diseases biomarkers in the retina. As an independent investigator, I am now focusing on the morphological and functional characterization of microglia in physiological and pathological conditions in brain and retina of patients and models of neurodegenerative diseases. I m working on the possibility to use the eye as a window on the brain for the early diagnosis and monitoring of Alzheimer s and other neurodegenerative diseases characterized by the presence of misfolded protein aggregates. These observations defined novel biomarkers in the AD retina, and supported an emerging view using the eye as a window to monitor brain pathologies.

a) Grimaldi A, Brighi C, Peruzzi G, Ragozzino D, Bonanni V, Limatola C, Ruocco G, Di Angelantonio S. Inflammation, neurodegeneration and protein aggregation in the retina as ocular biomarkers for Alzheimer's disease in the 3xTg-AD mouse model. Cell Death Dis. 2018
b) Grimaldi A, Pediconi N, Oieni F, Pizzarelli R, Rosito M, Giubettini M, Santini T, Limatola C, Ruocco G, Ragozzino D, Di Angelantonio S. Neuroinflammatory Processes, A1 Astrocyte Activation and Protein Aggregation in the Retina of Alzheimer's Disease Patients, Possible Biomarkers for Early Diagnosis. Front Neurosci. 2019
c) Gupta VB, Chitranshi N, den Haan J, Mirzaei M, You Y, Lim JK, Basavarajappa D, Godinez A, Di Angelantonio S, Sachdev P, Salekdeh GH, Bouwman F, Graham S, Gupta V. Retinal changes in Alzheimer's disease- integrated prospects of imaging, functional and molecular advances. Prog Retin Eye Res. 2020
d) Latina V, Giacovazzo G, Cordella F, Balzamino BO, Micera A, Varano M, Marchetti C, Malerba F, Florio R, Ercole BB, La Regina F, Atlante A, Coccurello R, Di Angelantonio S, Calissano P, Amadoro G. Systemic delivery of a specific antibody targeting the pathological N-terminal truncated tau peptide reduces retinal degeneration in a mouse model of Alzheimer's Disease. Acta Neuropathol Commun. 2021

5. Generation and functional characterization of novel 3D neuronal constructs. I m currently working on the development and functional characterization of 3D in vitro models of human tissues derived from reprogrammed human cells.. We plan to generate novel 3D models of the human nervous system, including the brain cortex and the retina, to assess whether they can be used for drug testing and for developing new diagnostic tools.

a) Salaris F, Colosi C, Brighi C, Soloperto A, Turris V, Benedetti MC, Ghirga S, Rosito M, Di Angelantonio S*, Rosa A*. 3D Bioprinted Human Cortical Neural Constructs Derived from Induced Pluripotent Stem Cells. J Clin Med. 2019 Oct 2;8(10). pii: E1595. *equal contribution
b) Steimberg N, Bertero A, Chiono V, et al. iPS, organoids and 3D models as advanced tools for in vitro toxicology. ALTEX. 2020
c) Brighi C, Cordella F, Chiriatti L, Soloperto A, Di Angelantonio S. Retinal and Brain Organoids: Bridging the Gap Between in vivo Physiology and in vitro Micro-Physiology for the Study of Alzheimer's Diseases. Front Neurosci. 2020
d) Brighi C, Salaris F, Soloperto A, Cordella F, Ghirga S, de Turris V, Rosito M, Porceddu PF, D'Antoni C, Reggiani A, Rosa A, Di Angelantonio S. Novel fragile X syndrome 2D and 3D brain models based on human isogenic FMRP-KO iPSCs. Cell Death Dis. 2021

D. Research Support

POR FSE 2014-2020 - Regione Lazio -149.700
Bio3DBrain

Retinal correlates of Alzheimer s Disease
JointLab D-tails - Italian Institute of Technology. 300.000

Biology of protein aggregates and neurodegeneration markers.
JointLab for Advanced Microscopy CrestOptics - Italian Institute of Technology. 541.691

Fulbright 2019 World Learning The United States-Italy Fulbright Commission- 13.860 $
FSP-P005556

Telethon Grant 2020 - Telethon 240.000
GGP20037 *MCPI

Sapienza Università- 89.700
DECODE

Sapienza Università- 50.000
PAEAN

FESR POR Life 2020 Regione Lazio - 178.937 - Role: PI