Research: Modeling Tauopathy-associated neurodegeneration in human iPSC-derived 2D and 3D retinal cultures
Tau protein stabilizes microtubules, aids in axonal transport, influences synaptic plasticity, and preserves overall cellular homeostasis. Tau-associated mutations can cause the formation of toxic misfolded proteins, contributing to tissue damage. Cumulative evidence suggests that neuropathological changes begin years before cognitive decline onset. Histological examination reveals tau-related hallmarks in the retinas of Alzheimer's (AD) and Frontotemporal Dementia (FTD) patients. Despite ongoing research, the study of tauopathies in the retina remains an evolving field. Induced pluripotent stem cells offer a valuable tool for modeling tauopathies, aiding in the understanding of neurodegenerative disease mechanisms and the development of potential treatments. The aim of my project is to examine the impact of a FTD/AD-related tau mutation on iPSC-derived retinal models. Considering the role of tau in regulating the growth and differentiation of neurons, I examined the temporal development of retinal progenitor cells (RPC) and post-mitotic neurons by confocal immunofluorescence assay and Real Time qPCR. I also monitored features associated with neurodegeneration such as the phosphorylation state of tau residues. I investigated the formation of functional neural circuits in retinal neurons measuring Ca2+ oscillations. According to preliminary data, mutant cultures show impaired neurogenesis and cytoskeletal alterations, even in the early stage of differentiation.
PARTICIPATION TO FUNDED RESEARCH PROJECTS
1) TARDIS (TArgeting misfolded Retinal tau for early AlzheimeR’s DIsease diagnosiS).PRIN 2022 - MUR - PI Di Angelantonio - 2 years - 249.000 €
2) Third mission project focused on the rare disease Syngap1. Terza Missione Ateneo 2021 - 18 months - PI Di Angelantonio -10.000 €
3) JointLab IIT - Dtails 2024-2026 -18 months - PI Di Angelantonio -150.000 €
SEMINARS/MEETING/COURSES
-EMBO | EMBL Symposium on “Organoids: modeling organ development and disease in 3D culture”. Poster session. Heidelberg (Germany), October 18-21 2023;
-Brainstorming research assembly for young neuroscientists (BraYn). Poster session. Naples (Italy), September 27-29 2023;
-Incontri Ravvicinati Symposium - 1st National Congress on Rare Disease Syngap1. Progetto di terza missione, Sapienza University, Rome (Italy), June 20-21 2023. Certificate of attendance;
-Course “From Ramon y Cajal to CryoEM Course for Advanced Microscopy”, Sapienza University, January 30-31 2023. Certificate of attendance;
-Formazione trasversale sulle soft skills per giovani ricercatori, “Valorizzare i risultati della Ricerca: la tutela brevettuale in ambito accademico”, Sapienza University, December 12 2022. Certificate of attendance;
-Formazione trasversale sulle soft skills per giovani ricercatori, “Advanced Deep Learning”, Sapienza University, December 2 2022. Certificate of attendance;
-Formazione trasversale sulle soft skills per giovani ricercatori, “Introduction to ML/DL and to Pytorch”, Sapienza University, November 30 2022. Certificate of attendance;
-Formazione trasversale sulle soft skills per giovani ricercatori, “I principali programmi europei di finanziamento R&I”, Sapienza University, November 14 2022. Certificate of attendance;
-Formazione trasversale sulle soft skills per giovani ricercatori, “Collaborative project writing and networking in the context of Horizon Europe. Services and tools for supporting researchers”, November 4 2022. Certificate of attendance;
-3rd EpiEpiNet Annual Meeting. Poster session. Lisboa (Portugal), September 23-24 2022.
PATENT
Alberto Boffi, Silvia Di Angelantonio, Ylenia Gigante, Silvia Ghirga, Lorenza Mautone, Paola Baiocco. PCT/IB2023/059666. New ferritin-based delivery system for bodipy molecules. September 28 2023.
WORK EXPERIENCE
2021/2022. Affiliated Researcher at the Italian Institute of Technology (Center for Life Nano-& Neuro-Science, CLN2S, Rome);
2021/2022. Research Fellowship (sponsored by CRISEL INSTRUMENTS s.r.l.) on MICOLET - POR FESR LAZIO 2014-2020 project;
2021. Research Fellowship, Italian Institute of Technology (Center for Life Nano-& Neuro-Science, CLN2S, Rome);
2019/2020. Research Fellowship, University of Salerno, on RARE.PLAT.NET project.
EDUCATION AND TRAINING
2022-in progress. PhD in Life Science (XXXVIII cycle). Sapienza University of Rome;
2020/2021. II level Professional Master's Program of Stem cells and genome editing (u-stem) in memoriam of Paolo Bianco, (110/110 cum laude). Sapienza University of Rome;
2018. Professional habilitation as Biologist. University of Sannio-Benevento;
2015/2018. Master of Science degree in Biology. University of Salerno (110/110 cum laude);
2010/2015. Bachelor of Science degree in Biological Sciences. University of Ferrara.