Giulia Dematteis

I graduated in Chemistry and Pharmaceutical Technologies at UPO (Novara), in 2019. One year after I started the PhD in Drug Innovation, under the supervision of prof. Lim, working on calcium signaling in glial cells. the focus of my PhD project has been the study of  endoplasmic reticulum-mitochondria (ER-Mit) interaction in Alzheimer disease (AD). Indeed, alteration in ER-Mit interaction has been reported in different pathological condition, including AD models. One of the most important processes that takes place at the ER-Mit site is the ER to mitochondria Ca2+ transfer. However, the mechanisms and alteration of calcium transfer in different diseases conditions are far from understanding. To directly evaluate the effects of shortening ER-Mit distances on Ca2+ handling, we overexpressed in Hela cells, linkers that fix the ER-Mit distance at 5nm and 10nm. We observed a reduction of mitochondrial Ca2+ uptake both in the mitochondrial matrix and in the lumen of the cristae of the mitochondria, while ER [Ca2+] was not affected. We also reported reduced protein synthesis and metabolic activity, recapitulating alterations identified in AD astrocytes. Moreover, we designed a linker that fixes the ER-Mit distances at 20nm (20nm EML), the one supposed to promotes ER-Mit calcium transfer. We found that the expression of the 20nm EML promotes ER to mitochondria calcium transfer, increasing the basal calcium concentration in the lumen of the cristae, and ATP-induced calcium pick in the mitochondrial matrix.  These data correlates with an increased amount of calcium transfer units formed by IP3R and VDAC1, evaluated via proximity ligation assay. Cells expressing 20nmEML also display increased cellular metabolic activity, rescuing the alterations described in AD astrocytes. Indeed, our results suggest a causal role for the increased ER-Mit interaction in AD related astroglial dysfunction, indicating that normalizing calcium transfer between ER-Mit could represent a valuable strategy for AD treatment. 

After having defended my PhD thesis (February 2023), in September 2023 I moved to Bordeaux, where I joined the team lead by Dr. Marsicano, at the Neurocentre Magendie (INSERM). Here I started a project, supported by the Fyssen foundation,  aimed to evaluate the role of cannabinoid system in the modulation of astroglial calcium signaling and trough modulation of ER-Mit interactions, and its impact on mice social behavior. Moreover, since September 2025, I'm responsible of a shared project between UPO and the Neurocentre Magendie, financed by Cariplo foundation, focused on investigating astroglial cannabinoid signaling as a potential target in AD.