 | Paola PizzoAssociate Professor of Pathology - Department of Biomedical SciencePhone: 049/8276067
Email: paola.pizzo@unipd.it
Address: Department of Biology - A. Vallisneri
II floor - North wing, Room 61
Via Ugo Bassi 58/B, Padova 35131 |
Our research activity is focused on cellular calcium (Ca2+) signalling, in both health and disease, with special attention on organelle Ca2+ handling and function. By combining biochemistry, molecular biology and imaging approaches, both in vitro and in vivo, we deeply investigate specific Ca2+ signalling pathways in normal and pathological conditions, especially in neurodegenerative disorders, such as Alzheimer’s Disease (AD), by exploiting different AD mouse models, and Hereditary Spastic Paraplegia (HSP), using Drosophila melanogaster as model organism. To address these goals, we also generate novel, state-of-the art, tailored-made Ca2+ (but also different ion and metabolite) biosensors.
Specific lines of research:
1) Unravelling the role of mitochondrial (dys)function in AD pathogenesis. Our research covers mitochondrial Ca2+ handling, organelle coupling with other intracellular structures, and organelle metabolism/bioenergetics at different disease stages in AD mouse models. We are also interested in verifying possible links between mitochondrial defects and behavioral impairment.
2) Ca2+ homeostasis defects and neuroinflammation in AD models. Cytosolic and organelle Ca2+ handling is studied in AD cell and animal models, not only in neurons but also in glial cells, both in vitro and in vivo. The role of microglia and astrocyte activation, release of inflammatory molecules and defective Ca2+ homeostasis is also investigated in AD mice.
3) Modeling neurodegenerative disorders in Drosophila melanogaster. We use Drosophila as a model to study the neurodegenerative disorder HSP. We are focused on understanding how ER shape-impairment, due to HSP gene mutations, affects specific ER functions.
4) Subcellular indicators. We are interest in the generation of chemical and genetically-encoded biosensors, for both Ca2+ and other ions and metabolites, targeted to specific subcellular locations to finely dissect intracellular signalling pathways. These tools are instrumental for determining a high-resolution map of the heterogeneity of signalling pathways within the cell. Furthermore, we develop tools to manipulate the functions of organelles, exploiting state-of-the-art methods, such as optogenetics.
Rossi A. et al., 2021. Calcium signaling and mitochondrial function in Presenilin 2 knock-out mice: looking for any loss-of-function phenotype related to Alzheimer’s disease. Cells, 10(2), 204.
Plotegher N et al., 2021. Excitotoxicity revisited: mitochondria on the verge of a nervous breakdown. Trends Neurosci, 16:S0166-2236(21)00013-8.
Rossi A. et al., 2020. Defective mitochondrial pyruvate flux affects cell bioenergetics in Alzheimer’s disease related models. Cell Reports, 30(7):2332-2348.e10.
Fedeli C et al., 2019. PSEN2 (presenilin 2) mutants linked to familial Alzheimer disease impair autophagy by altering Ca2+ homeostasis. Autophagy, 20:1-19.
Greotti E et al., 2019. Familial Alzheimer’s Disease-linked Presenilin mutants and intracellular Ca2+ handling: a single-organelle, FRET-based analysis. Cell Calcium, 79:44-56.
Theurey P et al., 2019. Systems biology analysis identifies impairment of mitochondrial and glycolytic metabolism in a genetic model of Alzheimer’s disease. Aging Cell, 18(3):e12924.
Vajente N et al., 2019. Microtubules Stabilization by Mutant Spastin Affects ER Morphology and Ca2+ Handling. Front Physiol, 10:1544.
Filadi R et al., 2016. Presenilin 2 modulates endoplasmic reticulum-mitochondria coupling by tuning the antagonistic effect of mitofusin 2. Cell Reports,15(10):2226-38.
Greotti E et al., 2016. Characterization of the ER-Targeted Low Affinity Ca2+ Probe D4ER. Sensors (Basel), 16(9):1419.
Filadi R. et al., 2015. Mitofusin 2 ablation increases endoplasmic reticulum-mitochondria coupling. Proc Natl Acad Sci USA 112(17):E2174-81.
Cariparo Progetti di Eccellenza- Early dysfunctions of astrocytic calcium signaling in Alzheimer's disease (2018-2021).
Progetti di Ricerca di Rilevante Interesse Nazionale - Early dysfunction of intercellular signaling in brain disorders. (2018-2021).
Telethon Grant GGP19304 – Plasmalogen-based therapeutic strategy for the treatment of Hereditary Spastic Paraplegia (2019-2022).
University of Padua Grant 2019 - Mitochondrial metabolism in Alzheimer’s disease (2019-2021).
Italian Ministry of Research Grant, (PRIN 2017) - A shape to fit the need: how cells rearrange their organelle composition and architecture during development and stress (2020-2023).
Cure Alzheimer’s Fund (USA), 2021 - Extracellular ATP is a key factor in promoting Alzheimer’s disease neuroinflammation (2021-2022).
