- Multi-omics investigation of extracellular vesicles from human iPSC-derived brain organoids containing microglia to understand gender specific Alzheimer’s Disease physiopathology (FIS-2 Starting Grant)
The 3DOMICS4AD project aims to investigate the molecular and cellular mechanisms underlying Alzheimer’s disease, with a particular focus on gender-specific differences in its pathophysiology. Three-dimensional brain organoids will be generated from induced pluripotent stem cells (iPSCs) derived from male and female patients, incorporating also the microglial component, which is often lacking in standard models. This innovative approach will enable the characterization of the cytoarchitecture and cellular organization within these 3D structures through multi-omics strategies, with a specific emphasis on the cargo of extracellular vesicles (EVs), key regulators of intercellular communication. The main goal is to delineate a gender-dependent molecular map of proteins, metabolites, miRNAs, and Aβ isoforms, in order to clarify their contribution to disease progression. Ultimately, the results will support the identification of sex-specific biomarkers and therapeutic targets, advancing our understanding of Alzheimer’s disease.
Alzheimer’s disease (AD) is the most common form of neurodegenerative dementia. Extracellular vesicles (EVs) released by neural stem cells (NSC-EVs) have shown a remarkable ability to modulate neuroinflammation in neurodegenerative diseases, as well as to promote neurogenesis and improve cognitive functions. This study primarily aims to analyze adult neurogenesis in detail in vitro, using primary neurosphere cultures derived from the 5XFAD AD animal model, which is known for its early-onset and particularly aggressive phenotype. Subsequently, the EVs released by neurospheres will be characterized in terms of ultrastructural and morphological properties, as well as their inflamma-miRNA content. The functional characterization of these molecules will help identify potential biomarkers and therapeutic targets.
- Role of microglia in the spread of inflammation in Amyotrophic Lateral Sclerosis (ALS) (Granted by The ALS Association, in collaboration with Dr. Giampaolo Zuccheri, FaBiT)
Neuroinflammation is a crucial hallmark of ALS in which microglia play a key role through the phenotypic modulation it undergoes following the onset of the disease and the release of neuroprotective and/or neurotoxic factors. The aim of the project is to identify factors secreted by microglia through exosomes, characterize their role in the spread of inflammation in ALS and identify potential therapeutic targets.
- Tumor-associated macrophages as potential therapeutic target for glioblastoma (Granted by Fondazione Umberto Veronesi, in collaboration with Prof.Mario Buffelli, Università di Verona)
Glioblastoma is one of the most common and aggressive brain tumors affecting the Central Nervous System. The tumor microenvironment that surrounds the tumor cells is characterized by a heterogeneous cellular composition and microglial cells are up to 30% of the total cell population. In that environment, microglia acquire a pro-tumoral phenotype and do not recognize the tumor cells as intruder promoting their growth and migration. We are working on the crosstalk between microglia and glioblastoma cells, over time, in vivo. The final aim is to promote the microglia phenotypic shift toward an anti-tumor one able to reduce the proliferation of glioblastoma cells.
https://www.fondazioneveronesi.it/ricerca/i-nostri-ricercatori/francesca-massenzio
- Screening of small synthetic molecules with neuroprotective and immunomodulatory effect on microglia in collaboration with Prof.ssa Maria Laura Bolognesi and Dott.ssa Elisa Uliassi (FaBiT)
In collaboration with Prof.ssa Maria Laura Bolognesi and Dott.ssa Elisa Uliassi, we are performing the screening of small synthetic molecules able to protect neurons against toxic stimuli and promote the microglial shift toward the anti-inflammatory one.
