Marina García Bejarano
- NEUROSCIENZE
- Phd: 37th cycle
- Department of Clinical and Biological Sciences
- Matriculation number: 975305
Phd thesis
MANIPULATING GROWTH FACTOR EXPRESSION TO IMPROVE PERIPHERAL NERVE REGENERATION
Introduction to and justification for the topic studied
Peripheral nerve injury is a common event, followed by spontaneous nerve regeneration which can be successful if the nerve injury does not affect the structure of the nerve scaffold, while it is ineffective when the nerve injury is severe and the two nerve stumps are separated. When the gap between the stumps is large, a graft is necessary to bridge them. The gold standard technique is the autograft, which nevertheless presents some drawbacks. For this reason, artificial conduits are often used to bridge the two nerve stumps. Conduits are colonized by macrophages, which sense hypoxia and release vascular endothelial growth factor (VEGF), and by nerve fibroblasts, which release different factors, including soluble neuregulin1 (NRG1) and VEGF-A. Nerve fibroblasts express mainly NRG1 α isoform, Schwann cells mainly β isoform, but the different roles of these isoforms have not yet been fully elucidated.
VEGF-A stimulates angiogenesis, NRG1 stimulates Schwann cell dedifferentiation and migration. Newly formed blood vessels form a pathway on which newly generated Schwann cells migrate, soon reached by growing axons.
Regeneration within conduits is efficient as with autografts when the patient is young, the gap is small, and the injury repair is immediate. When the injured patient is older, the gap is long or the repair is delayed, macrophages, Schwann cells, nerve fibroblasts and endothelial cells are not able to release adequate amounts of the factors necessary for nerve regeneration. For this reason, aim of this PhD project will be to enrich nerve conduits with nanoparticles conjugated with recombinant soluble NRG1 and VEGF to obtain a controlled release of these factors when their expression is not enough to promote nerve repair. In addition, we will try to find out what the exact role of NRG1 α and β is by silencing each of these isoforms with siRNA, since it is not known exactly whether they have a different function in peripheral nerve regeneration.
Working hypothesis
After delayed nerve repair, or in old patients, or when the gap is long, nerve regeneration within conduits is not efficient for several reasons, including the inability of the nerve cells to release adequate amounts of factors promoting Schwann cell dedifferentiation and migration. For this reason, we hypothesize that conduit functionalization with nanoparticles conjugated with recombinant soluble NRG1 and VEGF-A could promote the nerve regeneration through the controlled release of these factors. In addition, it is believed that the existence of two NRG1 isoforms could give rise to different roles in nerve repair, so silencing both isoforms together or separately could shed light on more mechanisms by which regeneration occurs.
Research activities
Clinical, methodological and theoretical aspects of translational and cognitive neuroscience by Prof. Maurizio Giustetto, Prof. Adriano Chiò and Prof. Annamaria Berti (6 h, 20/01/22) - Toolbox Course. Online/In presence.
From neural cell excitability to brain circuit recording, visualization and manipulation by Prof. Benedetto Sacchetti, Prof. Franscesco Ferrini, Prof. Giulia Concina, Prof. Stefano Zucca and Prof. Serena Bovetti (10 h, 01/02/22; 08-15-22-29/03/22) - Toolbox Course. In presence.
Introduction to research methodology by Prof. Daniele Romano (12 h, 4-11-18-25/02/22) - Toolbox Course. Online.
Innovative and experimental therapies in movement disorders by Prof. Aristide Merola (The Ohio State University, USA) - Toolbox Course - Visiting Professorship:
- "Clinical and Pathological Basis of the most common Movement Disorders: Parkinsonisms, Dystonias, and Tremors". Online (17/02/22).
- Little talk about the future and professional opportunities in the academy and in an enterprise. Also we talked about the difference between the American and Italian systems. Online (03/03/22).
- "Observational and Experimental Studies for Therapeutic Interventions in Movement Disorders". Online (10/03/22).
- "Deep Brain Stimulation, Focused Ultrasound Ablation, and Gene Therapy". Online (18/03/22).
Brain stimulation for neurological diseases by Prof. Mario Rizzone, Prof. Carlo Alberto Artusi, Prof. Laura Avanzino, Prof. Giacomo Koch, Prof. Alberto Benussi and Prof. Marco Bozzali (12 h, 17/03/22; 07/04/22) - Toolbox Course. In presence.
Italian Language Course - BEGINNER LEVEL (A1-A2) by Prof. Elena Laura Baratono (20 h, 02/03/22-16/05/22). Online. Certificate obtained.
Corso di formazione generale per lavoratori in materia di igiene e sicurezza (D. Lgs. 81/08 s.m.i.) (4 h, 05/05/22). E-learning. Certificate obtained.
How we reason by Prof. Monica Bucciarelli (6 h, 18-25/05/21). Online.
Ethics of research and Responsible research: an introduction by Prof. Daniela Ovadia (8 h, 20-21/05/22). Online.
In vitro and ex vivo approaches to study rodent and human neural cells by Prof. Annalisa Buffo, Prof. Enrica Boda, Prof. Elena Parmigiani, Prof. Valentina Cerrato and Prof. Gianmarco Pallavicini (10 h, 28/06/22; 04/07/22).
Italian Language Course B1-B2 - Intermediate by Prof. Elena Laura Baratono (40 h, 11/09/23-20/11/23). Online. Certificate obtained.
II Curso sobre la carrera investigadora by Academia Joven de España - UNED - CSIC (9-19 h, 22/11/23). Online. Certificate obtained.
How to write a scientific paper by Dr. Lorenzo Galluzzi (Weill Cornell Medicine, New York) (11/03/2024). Organized by University of Zaragoza. Hybrid. Certificate obtained.
Experimental tissue models as sustainable tools to protect human health. Organized by Politecnico di Torino (29/04/2024). Workshop in presence. Certificate obtained.
"Importin alpha3 regulates chronic pain pathways in peripheral sensory neurons" by Letizia Marvaldi (Weizman Institute of Science, Israel). NICO NeuroWebinar (12/11/21, date changed to 18/11/21).
"From advanced cell culture studies to a stem cell therapy for Parkinson's disease" by Alessandro Fiorenzano (ULUND). NICO NeuroWebinar (19/11/21).
"Changes in plasticity during postnatal development. Opening and closing plasticity windows" by Antonio Rodríguez Moreno (Universidad Pablo de Olavide, Spain). NICO NeuroWebinar (25/11/21).
"Aconitase2 is a marker of mitochondrial dysfunctions in Spinal Muscular Atrophy spinal cord and fibroblasts" by Serena Stanga (Group Vercelli). NICO NeuroWebinar (03/12/21).
"The effect of cerebrospinal fluid in collagen guide channel on sciatic nerve regeneration in rats” by Dr. Mohammad Amin Dolatkhah (University of Tabriz, Iran). Online (07/12/21).
"Cell signaling pathways in autosomal-dominant leukodystrophy (ADLD): the intriguing role of the astrocytes" by Giulia Ramazzotti (University of Bologna, Italy). NICO NeuroWebinar (28/01/22).
PhD in Neuroscience: "Data Report for the XXXVI cycle". Online (15/02/22).
"Collective behavior and hippocampal activity in freely forging bats" by Angelo Forli (University of California, USA). NICO NeuroWebinar (04/03/22).
"Astrocyte dysfunction in ASD" by Dilek Colak (Cornell University, USA). NICO NeuroWebinar (18/03/2022).
"Face anatomy and related aesthetic conditions" by Mustafa Aktekin (Acibadem University, School of Medicine, Istanbul Turkey). In presence (27/04/22).
"Breaking the stigma on Academic Mental Health" by Stefano Zucca (Group Peretto - Bonfanti). NICO NeuroWebinar (13/05/22).
Seminario de seguridad en las instalaciones del Instituto de Investigación de Nanociencia de Aragón -SegurINA- (6-8/06/22).
PhD in Neuroscience: "Data Report for the XXXVII cycle" (incuding my presentation). Online (15/02/23).
“Neuropathy and dementia: two diseases with a common cause” by Eva Feldman (Peripheral Nerve Society). Online (5/05/2023).
Every Thursday (currently, before every Monday) there is a seminar of the Bionanosurf group in Zaragoza, Spain. I had to give it on 24/10/2022, telling my research experience, as well as my research project.
“Breaking Through Transfection Barriers Innovative Strategies for Effective siRNA Delivery in Complex Cell Models” by Dr. Johanna De Castro Arce (Carlo Erba Reagents, Horizon - Dharmacon). Online (10/11/2023).
"Unlocking the Transcriptome: A Journey into RNA Sequencing" by Carolina Jiang Zheng (Product Marketing Manager, Novogene). Online (30/11/23). Attendance certificate obtained.
"Mitochondrial alterations in Alzheimer's disease: insights from the 3xTg Mouse Model" by Elif Keshinoz (Department of Anatomy, School of Medicine, Acibadem Mehmet Ali Aydinlar University, Istanbul, Turkey). NICO NeuroWebinar. In presence (30/11/23).
Welcome meeting XXXIX cycle and 2nd ‘Enrica Marzola’ Award Ceremony. In presence (30/11/23).
"Macrophage activation within Cervical Cancer microenvironment is associated with better prognosis" by Dr. Laurent Gorvel (Cancer Research Center of Marseille, France). Webinar organized by React4Life. Online (14/02/24).
PhD in Neuroscience: "Data Report for the XXXVIII cycle". Online (15/02/24).
"Nuovi orizzonti nella rigenerazione dei nervi: il futuro della ricerca" by Stefania Raimondo, Giulia Ronchi and Giovanna Gambarotta (Department of Clinical and Biological Sciences, UNITO, Italy). Live organized by TrendSanità. Online (16/02/24).
"Regulation of RNP granule dynamics and axonal translation in sensory and motor neurons" by Marco Terenzio (OIST - Okinawa Institute of Science and Technology, Japan). Hybrid seminar. In presence (01/03/2024).
"Designing biofunctional nanoparticles" by Jesús Martínez de la Fuente (Institute of Nanoscience and Materials of Aragon, CSIC-University of Zaragoza, Zaragoza, Spain). Hybrid seminar (14/03/2024).
"Using fNIRS to investigate the development of functional connectivity and its relationship with social development and early adversity" by Dr. Chiara Bulgarelli (ToddlerLab, Birkbeck, University of London, UK). Hybrid seminar (16/04/2024).
MSc Cellular and Molecular Biology thesis defense session (16/04/2024).
"Neuron-glia metabolic coupling: role in neuronal plasticity and neuropsychiatric disorders" by Pierre J. Magistretti (KAUST, Thuwal, Saudi Arabia). NICO NeuroWebinar (19/04/2024).
Researchers' Night 2022 (5h, 30/09/2022). My task in this workshop was to report on the lines of research of the Bionanosurf group in Zaragoza (Spain), as well as carry out activities with children to teach basic science at a microscopic level. Certificate obtained.
Researchers' Night 2023 (5 h, 29/09/2023). I carried out a scientific dissemination activity, called “Nanoeye” of workshops for children about nanoscience in Zaragoza, Spain. Certificate obtained.
ISPNR 2022: 6th Symposium on Peripheral Nerve Regeneration. 7th-8th July 2022 - UCL, London, UK. Poster presented: Regulator of G Protein Signalling (RGS16) is upregulated after peripheral nerve injury.
Workshop en Materiales con Funcionalidades Avanzadas para la Nueva Transformación Tecnológica. 5th-7th September 2022 – Albarracín, Teruel, Spain. Poster presented: Conduit functionalization with nanoparticles for the controlled release of factors promoting nerve regeneration.
XVI European Meeting on Glial Cells on Health and Disease. 8th-11th July 2023 - Berlin, Germany. Poster presented: A novel protein involved in peripheral nerve injury: Regulator of G Protein Signalling 16 (RGS16).
20th National Congress of the Italian Society for Neuroscience. Satellite Events Day. 14th September 2023 - Torino, Italy. Poster presented: Nanocarriers as vectors to up- or down-regulate signal transduction pathways in peripheral nerve regeneration.