ILARIA MARINA MICHELOZZI

Biography

Alterations in the haematopoietic system have always been the focus of my research.
During my PhD, I investigated the role of the bone marrow (BM) microenvironment in the pathogenesis and in the chemoresistance of haematological disorders. Using an in vivo BM niche model, I demonstrated that mesenchymal stromal cells (MSC) derived from aplastic anaemia paediatric patients were able to form a complete and functional BM niche in vivo, excluding their role in the initiation of the disease (Michelozzi IM et al., British Journal of Haematopoiesis, 2017). Furthermore, I tested the toxicity of L-asparaginase on acute myeloid leukaemia (AML) cells, especially on leukaemic stem cells (LSC). Whilst it was effective on AML blasts and LSC-enriched compartments, MSC and monocytes/macrophages partially counteracted the effect of the drug providing a protective niche (Michelozzi IM et al., British Journal of Haematopoiesis, 2019).
These findings are of clinical relevance for the comprehension of the pathogenesis and for the treatment optimisation of haematological diseases.
In addition to this, I have also contributed to the generation of a novel affordable AML xenograft model testing a new conditioning regimen (irradiation plus fludarabine injection) in Scid-beige mice (Pievani A et al., Scientific Reports, 2018).
Currently, my post-doctoral studies revolve around the development and molecular characterisation of Chimeric Antigen Receptor (CAR)-T cells, new and very promising therapeutic tools against haematological malignancies. By applying RNA-sequencing and mass cytometry, I identified an anti-CD19 CAR effectiveness-related molecular signature that can be used as a reference to predict the functionality of newly designed CAR-T cell products (Michelozzi IM et al., BioRxiv, 2020; Michelozzi IM et al., STAR protocol, 2022). Furthermore, I am working on the optimisation of CAR constructs against AML (Michelozzi IM et al., Cancers, 2021). Specifically, I am setting up a multi-omics technology to identify at single-cell level the optimal combination of surface markers on AML blasts to be targeted with CAR-T cells.