My research interests are focused on how positive-sense single-strand RNA (+ssRNA) viruses, such as SARS-CoV-2, co-opt cellular machineries and remodel cellular organelles to create and environment conducive to viral replication. SARS-CoV-2 replicates its genome in the cytosol in close association with the cellular endomembrane system. Viral proteins, together with host factors, remodel ER membranes to drive the formation of the viral replication organelles (ROs), a virus-induced specialized compartment in which viral genome replication takes place. Due to their central role in viral replication, ROs are attractive candidates for antiviral therapy. Our integrated imaging approach identified a large spectrum of physio-pathological changes associated with SARS-CoV-2 infection, revealing extensive fragmentation of the Golgi apparatus, alteration of the mitochondria morphology, recruitment of peroxisomes to the ROs, and reorganization of the cytoskeleton. However, the functional relevance of such alterations and the molecular mechanisms governing their induction are still largely unknown. In our laboratory, we will combine molecular virology, cell biology and advanced imaging approaches to understand the molecular mechanisms driving ROs biogenesis and virus-induced membrane remodeling.
The final objective of the research project is to identify the key molecular constituents and mechanisms that regulate SARS-CoV-2-induced cytopathogenicity, host-cell alterations and response to infection, with the overall goal of finding ways to limit virus infection and/or reduce the severity of the virus-associated disease.
As SARS-CoV-2 continues to spread, virus variants that diverge from the early isolates are increasingly being identified. Using physiologically relevant cell culture models, we will evaluate the impact of SARS-CoV-2 evolution on cellular pathogenesis and humoral immune evasion and correlate these results to virus transmissibility, clinical pathology, and disease severity.
Quote
I’ve recently joined the TIGEM faculty and I have found awesome scientists, great infrastructure, and excellent support. I cannot wait to start this new exciting adventure.
Additional Funding
- FTH - FONDAZIONE HUMAN TECHNOPOLE - AAV vectors in the Human Central Nervous System (2023)