Development and Validation of a Phosphoproteomics Analysis Pipeline for the Characterization of Targetable Kinases in Myeloid

Myelodysplastic syndromes (MDS) are heterogeneous clonal disorders of the hematopoietic stem cells characterized by dysplasia, cytopenia and the ability to progress towards AML. Many driver mutations have been identified in the last years, however, their contribution to the oncogenic phenotype is not fully understood. The aim of my PhD project is to develop a bioinformatics tool that takes phospho-/proteomic data as input to identify/characterize involved oncogenic pathways that drive/maintain the neoplastic phenotype and to establish a network analysis to identify potential targets for personalized treatment. Therefore, the phospho-/proteome analysis will be the main focus in this project followed by the integration with more established analyses on DNA/RNA profiles. The plan is to use the phospho-/proteomic profiles from AML cell lines to build a preliminary bioinformatics pipeline for the identification and characterization of signaling pathways. After the establishment of this pipeline, data from primary MDS/AML samples will be tested where the pipeline will be modified accordingly. In an extension to the project, the genomic data (DNA/RNA) shall be integrated to improve the level of identification and prediction. The project will lay the foundation to establish a bioinformatics tool that would be able to identify potential biomarkers for personalized treatment in MDS/AML by in-silico modelling of oncogenic pathways. The project has, therefore, a high translational potential, since identified pathways can then potentially be targeted by specific compounds to foster personalized treatment.