Elisa Tonelli

Elisa Tonelli is a 1^st year PhD student in Experimental neuroscience since January 2024, working under the supervision of Dr. Cristina Meregalli on a project aimed at uncovering molecular mechanisms of chemotherapy-induced peripheral neuropathies (CIPN). Before arriving at University of Milano-Bicocca, she studied at University of Eastern Piedmont, where she obtained a Bachelor’s degree in Biotechnologies in March 2021 with an experimental thesis entitled “Biochemical characterization of the knockout of a Ca²⁺-dependent phosphatase, calcineurin, in a line of fetal human astrocytes”, followed by a Master’s degree in Medical biotechnology in October 2023 with an experimental thesis entitled “Investigation of Ca²⁺ transfer between ER and mitochondria using artificial linkers: a case of hepatocellular carcinoma cell line”. There, she had the opportunity to work in the Physiology lab of Prof. Dmitry Lim, where she became familiar with cell culture handling and the most routinely used biochemical/molecular biology techniques. Additionally, during her Master’s internship she gained some expertise in cell transfection and in intracellular Ca²⁺ imaging (exploiting both dyes and genetically-encoded probes), that she is now applying on her current work on CIPN. Despite her background almost exclusively relying on in vitro techniques, she is now approaching also in vivo studies in order to improve her skills as a researcher.

PhD research project

Interplay between neuroactive steroids and endoplasmic reticulum-mitochondria interaction: a novel therapeutic horizon in CIPN

Chemotherapy (CT)-induced peripheral neuropathy (CIPN) is a common adverse effect of the treatment with different classes of chemotherapeutic agents and it manifests as a set of sensory-related symptoms. It is estimated that around 60-70% of patients undergoing CT experience these symptoms, that might be so disabling to force them to CT dose reduction or treatment withdrawal. At the cellular level, CT is well known to exert neurotoxic effects over sensory neurons and peripheral glial cells, but the precise molecular mechanisms by which it induces damage to these cells are poorly understood. Noteworthy, mitochondria have been reported as targets of several chemo-based regimens, both in terms of their morphology/motility and of their specific functionality, essential for the maintenance of cellular homeostasis. In the context of mitochondria, growing body of evidence highlights the relevance of ER-mitochondria interaction, which takes place at the level of complex morpho-functional units known as mitochondria-ER contact sites (MERCS). Therefore, a promising strategy to unveil CIPN molecular mechanisms could be represented by a focused analysis of the possible effects of antineoplastic drugs at the level of MERCS in both sensory neurons and glial cells. To achieve this goal, we are investigating MERCS structure and functionality upon treatment with different classes of chemotherapeutic agents, firstly in F11 and MSC80 cell lines (chosen as models for sensory neurons and peripheral glial cells, respectively) and next in primary cells. Then, once identified possible mechanisms altered by CT, we will try to correct them (first in vitro and then in vivo) by employing neuroactive steroids (NAS), a class of endogenous cholesterol derivatives that have already been reported to have beneficial effects over neurons in different subtypes of peripheral neuropathies.