Biomedical subjects

Ivan Merelli

Publications and source records attributed to Ivan Merelli.

3 recordsLinked to original sources

PubMed2026

Therapy induced senescence promotes immunogenicity in acute myeloid Leukemia through reduced EZH2 activity.

Chemotherapy resistance and disease relapse are major determinants of treatment failure in acute myeloid leukemia (AML). Therapy-induced senescence (TIS) is one outcome of chemotherapy, but its immunological consequences in AML remain unclear. Here we show that ex vivo chemotherapy induces senescence in a subset of therapy-naïve AML samples. TIS is marked by elevated interferon signaling, upregulation of human leukocyte antigen (HLA) class I and II molecules, and increased presentation of leukemia- and senescence-associated peptides, conferring AML cells antigen-presenting cell-like features. These changes enhance autologous CD4+ and CD8+ T cell responses against AML, both ex vivo and in patient-derived xenograft models. TIS also restores AML sensitivity to immune checkpoint blockade therapy. Mechanistically, we identify reduced Polycomb Repressive Complex 2 (PRC2) activity as central to TIS induction and its immunogenicity. PRC2 inhibition reactivates senescence-related genes and HLA expression in non-senescent AML cells, enabling T cell activation. These findings uncover a senescence-driven immune mechanism with potential to improve therapy outcomes in AML.

Humans↗

PubMed2005

High performance workflow implementation for protein surface characterization using grid technology.

BACKGROUND: This study concerns the development of a high performance workflow that, using grid technology, correlates different kinds of Bioinformatics data, starting from the base pairs of the nucleotide sequence to the exposed residues of the protein surface. The implementation of this workflow is based on the Italian Grid.it project infrastructure, that is a network of several computational resources and storage facilities distributed at different grid sites. METHODS: Workflows are very common in Bioinformatics because they allow to process large quantities of data by delegating the management of resources to the information streaming. Grid technology optimizes the computational load during the different workflow steps, dividing the more expensive tasks into a set of small jobs. RESULTS: Grid technology allows efficient database management, a crucial problem for obtaining good results in Bioinformatics applications. The proposed workflow is implemented to integrate huge amounts of data and the results themselves must be stored into a relational database, which results as the added value to the global knowledge. CONCLUSION: A web interface has been developed to make this technology accessible to grid users. Once the workflow has started, by means of the simplified interface, it is possible to follow all the different steps throughout the data processing. Eventually, when the workflow has been terminated, the different features of the protein, like the amino acids exposed on the protein surface, can be compared with the data present in the output database.

Automation↗

PubMed2005

Representation and modeling of protein surface determinants.

Surface characterization of peptides may provide useful information about functionality and potential interactions with other molecules. A description of a protein site through a surface that models the shape conferred by the exposed residues is an effective tool for the analysis and the modeling of proteins that may highlight similarities and relationships not detectable through comparisons at level of primary, secondary, and tertiary structure. This study concerns the development of a tool that extracts the residues that concur to the shape modeling of the surface of a protein or a portion of it. This task is accomplished without taking into account the order of the amino acids in the primary structure, but only according to the selection of a portion of the protein indicated through geometric parameters or an explicit list of amino acids belonging to the site of interest. Both in the case of an entire protein and in the case of a portion of it, the method provides the mesh that models the surface described by the exposed residues that constitute the external envelope. The developed tool which allows the extraction of the exposed residues, and thus of the potential function determinants, is applied to identify the amino acids that concur to the structural interaction in several protein complexes.

Amino Acid Sequence↗