Cilia and Human Diseases
Cilia are evolutionary conserved organelles and have crucial roles in cell signalling pathways and in maintaining cellular homeostasis. Thousands of proteins potentially involved in ciliary function have been identified. However, much remains to be determined on the biology and functions of this complex organelle of growing biomedical importance.
Our laboratory aims at addressing the following questions:
- Why mutations in the same transcript can cause phenotypes ranging from the involvement of single tissues to a wide spectrum developmental disorder such as OFD type I syndrome?
- Do cilia have a role in oncogenetic events?
Mitochondria and mitochondrial disorders
Mitochondrial dysfunction underlies the pathogenesis of rare and common conditions. Our laboratory focuses on different aspects of mitochondria biology and mitochondrial disorders. We aim to:
- Study the mechanisms underlying the neuroprotective effect of miRNA181a and miRNA 181b downregulation in mitochondria-mediated neurodegeneration (e.g. Leigh and LHON syndromes)
- Dissection of a novel mitochondrial caspase mediated cell death pathway implicated in human diseases
Rare tumors
We recently launched the MOSTRA (Multi-Omics Study Rare Tumors) project. This project proposes the use of multi-omics technologies for the molecular characterization of rare tumors, using biopsy material from patients. The main objectives are a) identification of new biomarkers for precision medicine in rare tumors; b) identification of new molecular targets; c) identification of new therapies.
We anticipate that, through the integration of multi-omics techniques will allow us to recognize different cell subpopulations within the same tumor. The results obtained will consent to determine the origin, evolution, and spread of the cancer process, starting from a minimal sample quantity.
Moving a candidate gene to the next step
In collaboration with the Telethon Undiagnosed Disease project (TUDP) we aim at assessing the pathogenicity of candidate disease gene, downstream the classical genetic approaches, including GeneMatcher-based ones. Our approach will include:
- In silico tools, which will consist in a) assessment of the expression patterns of candidate genes; b) co-expression analysis followed by Gene Ontology and Pathway enrichment analysis
- In vitro assays to validate the involvement of the candidate gene in the disease under study. This approach will include a) Knock-out and/or knock-in of genes and/or specific mutations obtained by CRISP-Cas9; b) Suitably tagged (GFP and/or HA) cell lines generated for further functional characterization; c) patients’ fibroblasts to generate iPS and differentiated cells.
- In vivo validation in fish models (zebrafish or medaka fish) or C. elegans.
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I joined TIGEM in 1994 and I scientifically grew within TIGEM. I started my career as a human geneticist and while I was originally involved in the identification of disease genes, I then shifted my scientific interest toward more functional studies. I want to understand how and why a disease affects specific individuals and tissues and possibly offer solutions. I also enjoy in witnessing and mentoring the flourishing of young researchers around me and TIGEM is the ideal place in terms of opportunities and research environment.
Additional Funding
- AIRC - The primary cilium as a therapeutic target in bile duct cancer (2023-2024)
- Modulazione dei miR181a/b come approccio terapeutico a malattie neurodegenerative associate a disfunzione mitocondriale (2021-2022), Banca d'Italia
- Therapeutic efficacy of miR-181a/b down regulation in Leigh syndrome (2020-2021), United Mitochondrial Disease Foundation