Hybrid seminar

Friday 13/3/2026  h. 2.00 pm

Michela Fagiolini
Istituto di Neuroscienze CNR, Harvard Medical School and Boston Children’s Hospital

Circuits dissection in neurodevelopmental disorders from mechanisms to therapeutic windows

Neurodevelopmental disorders such as Rett syndrome and CDKL5 deficiency disorder are severe monogenic conditions characterized by early-onset cognitive impairment, sensory dysfunction, and epilepsy, yet effective disease-modifying therapies remain limited. My research aims to dissect the circuit and cellular mechanisms that link gene mutations to network dysfunction and behavioral phenotypes, with the goal of identifying actionable therapeutic targets.

Using an integrative translational framework, we combine advanced genetic models, in vivo circuit interrogation, high-resolution imaging, electrophysiology, and quantitative behavioral phenotyping to map how disruptions in MECP2 and CDKL5 signaling alter sensory processing, cortical plasticity, and brain-wide connectivity across development. These approaches enable the identification of convergent pathophysiological pathways, including altered excitation–inhibition balance, impaired neuromodulatory control, and deficits in experience-dependent plasticity.

Importantly, our work bridges mechanistic discovery with therapeutic exploration by testing circuit-based interventions and molecular strategies designed to restore network function and reopen critical periods of plasticity. By integrating preclinical and clinical investigations, this research provides a framework for precision medicine approaches aimed at improving functional outcomes in individuals with Rett syndrome and CDKL5 deficiency disorder.

Michela Fagiolini, PhD, is a neuroscientist whose research focuses on understanding how genetic mutations disrupt brain circuit development and sensory processing in neurodevelopmental disorders. She serves as Director of the Institute of Neuroscience at the Italian National Research Council (CNR) and holds an academic appointment at Harvard Medical School and Boston Children’s Hospital.

Her work integrates molecular, circuit, and behavioral approaches to investigate disorders such as Rett syndrome and CDKL5 deficiency disorder, with the goal of identifying mechanisms of network dysfunction and developing targeted therapeutic strategies. Dr. Fagiolini has contributed to advances in the study of experience-dependent plasticity, critical period regulation, and translational approaches linking basic neuroscience to clinical research.

Host: Alessandro Vercelli