c/o Complesso Biologico Interdipartimentale
Viale Giuseppe Colombo 3
Over the last years I’ve been involved in studying calcium (Ca2+) signalling both in health and disease. My research focused on the development of new tools to explore the mitochondrial functionality, and in particular mitochondrial Ca2+ dynamics, in vivo. Therefore, I worked on the improvement of mitochondria-targeted Ca2+ probes and the creation of a new mitochondria-targeted Channelrhodopsin.
These methodologies are instrumental for addressing with novel approaches the role of second messenger heterogeneity in different pathophyiological conditions not only in cell cultures, but also in tissue preparations (acute slices) and in vivo. Currently, I'm interested in studying Familial Alzheimer's Disease (FAD), focusing on the imbalance of cellular Ca2+ homeostasis. Indeed Alzheimer’s disease (AD) is the most frequent form of dementia, a small percentage of cases is inherited (Familial AD, FAD), due to dominant mutations on three genes, encoding for Amyloid Precursor Protein (APP), Presenilin-1 (PS1) and Presenilin-2 (PS2). PS1 and 2 are the catalytic core of the γ-secretase complex, but they are also involved in other γ-secretase-independent processes, such as Ca2+ homeostasis. Beside the current hypothesis about amyloid and tau hyperphosphorylated, cellular Ca2+ alterations have been reported to contribute to the AD pathogenesis.
Different studies reported a role for FAD-linked PSs mutations in Ca2+ signalling alterations, often independently from their role in γ-secretase activity. However, despite many efforts done in the last years, the role of PSs in Ca2+ homeostasis is still debated in the scientific community. The final goal is the employment of these newly created tools to perform in vivo Ca2+ measurements in different tissues and subcellular compartments in animal models of AD.
Member of group: Ca2+ and cAMP signalling in physiology and pathology
Tkatch T, Greotti E, Baranauskas G, Pendin D, Roy S, Nita LI, Wettmarshausen J, Prigge M, Yizhar O, Shirihai OS, Fishman D, Hershfinkel M, Fleidervish IA, Perocchi F, Pozzan T, Sekler I., Optogenetic control of mitochondrial metabolism and Ca2+ signaling by mitochondria-targeted opsins. Proc Natl Acad Sci U S A. 2017 Jun 13. pii: 201703623. doi: 10.1073/pnas.1703623114. PMID:28611221
Pendin D, Greotti E, Lefkimmiatis K, Pozzan T., Exploring cells with targeted biosensors. J Gen Physiol. 2017 Jan;149(1):1-36. doi: 10.1085/jgp.201611654. Epub 2016 Dec 27. Review. PMID: 28028123
Greotti E, Wong A, Pozzan T, Pendin D, Pizzo P., Characterization of the ER-Targeted Low Affinity Ca(2+) Probe D4ER. Sensors (Basel).
2016 Sep 2;16(9). pii: E1419. doi: 10.3390/s16091419.PMID:27598166
Filadi R, Greotti E, Turacchio G, Luini A, Pozzan T, Pizzo P., Presenilin 2 Modulates Endoplasmic Reticulum-Mitochondria Coupling by Tuning the Antagonistic Effect of Mitofusin 2. Cell Rep. 2016 Jun 7;15(10):2226-38. doi: 10.1016/j.celrep.2016.05.013. Epub 2016 May 26.PMID:27239030
Filadi R, Greotti E, Turacchio G, Luini A, Pozzan T, Pizzo P., Mitofusin 2 ablation increases endoplasmic reticulum-mitochondria coupling.
Proc Natl Acad Sci U S A. 2015 Apr 28;112(17):E2174-81. doi: 10.1073/pnas.1504880112. Epub 2015 Apr 13.PMID: 25870285