Iannielli Angelo
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Technologist
Via Olgettina 58
20132 Milano
Tel 02-26434612
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My research interests are expansive in the field neurodegeneration and stem cells differentiation.
In August 2014 I joined Vania Broccoli’s lab where I first focused on direct reprograming of human somatic cells into dopaminergic neurons. Next, I focused my interest on neurodegeneration and stem cells differentiation by studying fibroblasts-derived iPS cells from patients with genetic forms of Parkinson´s disease.
In particular I focused on genetic forms carrying mitochondrial dysfunction, for example mutations in OPA1 gene. We observed that iPSC-derived neurons with OPA1 mutation are more sensitive to death and presented abnormal mitochondrial distribution. Our hypothesis is that dysfunctional mitochondria are not able to move along the axons to provide the right amount of energy for synaptic activity.
To test this hypothesis, we decided to use a microfluidic platform for the in vitro reconstruction of networks in which each neuronal compartment (presynaptic, synaptic, and postsynaptic) is identified (space compartmentalization) and in which the progression from axonal growth to synapse regulation is controlled to understand this mechanism.
Last year, I focused my interest on blood brain barrier (BBB) and we established detailed procedures to differentiate hPSCs into endothelial, mural and astroglial cells to generate assembloids that recapitulate the organization of the BBB on transwell filters (tBBBA). Co-culture of brain endothelium, mural cells and astrocytes produced a robust in vitro neurovascular model with long-lasting stability and functions.
This defined differentiation procedures generate human tBBBAs that offer a system for modeling diseases of the brain vasculature as well as stringently testing new brain shuttling agents.
Publications
Maimaitili, M. Chen, F. Febbraro, E Ucuncu, R. Kelly, J.C. Niclis, J.R. Christiansen, N. Mermet-Joret, D. Niculescu, J. Lauritsen, A. Iannielli, I.H. Klæstrup, U.B Jensen, P. Qvist, S. Nabavi, V. Broccoli, A. Nykjær, M. Romero-Ramos, M. Denham. “Enhanced production of mesencephalic dopaminergic neurons from lineage-restricted human undifferentiated stem cells”. Nat Commun. 2023 Dec 5;14(1):7871. doi: 10.1038/s41467-023-43471-0
Pedrini*, A. Iannielli*, L. Meneghelli*, D. Passarella, V. Broccoli, P. Seneci. “Synthesis and Preliminary Characterization of Putative Anle138b-Centered PROTACs against α-Synuclein Aggregation”. Pharmaceutics 2023 May 11;15(5):1467. doi: 10.3390/pharmaceutics15051467
Iannielli, M. Luoni, S. G. Giannelli, R. Ferese, G. Ordazzo, M. Fossati, A. Raimondi, F. Opazo, Ol. Corti, J.H M Prehn, S. Gambardella, R. Melki, V. Broccoli. “Modeling native and seeded Synuclein aggregation and related cellular dysfunctions in dopaminergic neurons derived by a new set of isogenic iPSC lines with SNCA multiplications”. Cell Death and Disease 2022 Oct 19;13(10):881. doi: 10.1038/s41419-022-05330-6
Iannielli, G. S. Ugolini, C. Cordiglieri, S. Bido, A. Rubio, G. Colasante, M. Valtorta, T. Cabassi, M. Rasponi, V. Broccoli. “Reconstitution of the human nigro-striatal pathway on-a-chip reveals that OPA1 mutations causes mitochondria localization defects and loss of dopaminergic synapses”. Cell Reports, (2019) Dec 24;29(13):4646-4656.e4. doi: 10.1016/j.celrep.2019.11.111
Iannielli, S. Bido, L. Folladori, A. Segnali, C. Cancellieri, A. Maresca, L. Massimino, A. Rubio, G. Morabito, L. Caporali, F. Tagliavini, O. Musumeci, G. Gregato, E. Bezard, V. Carelli, V. Tiranti, V. Broccoli. “Pharmacological Inhibition of Necroptosis Protects from Dopaminergic Neuronal Cell Death in Parkinson's Disease Models”. Cell Reports, (2018) Feb 20;22(8):2066-2079. doi: 10.1016/j.celrep.2018.01.089