The proposed PhD project aims to:

Explore the relevance of the m6A signaling pathway in neural tumors, such as neuroblastoma and glioblastoma, and identify possible new therapeutic strategies against these cancers. Specifically, the project focuses primarily on the role of the m6A readers, the YTH-containing proteins, in determining the stemness of cancer cells and envisions a differentiation-based therapy using investigational probes. In this frame, the modulation of the writer and eraser complexes might also be taken into account.

The main objectives of the project are:

1. Assess attenuation of m6A decoding by genetic knockout of m6A-related proteins and perform phenotypic characterization.

2. Assess attenuation of m6A signaling by treatment with probes targeting the m6A-related proteins.

The Doctoral Candidate is expected to achieve relevant results in the following areas:

1. Establish cellular models of single or triple YTHDF knockouts for Glioblastoma and Neuroblastoma cell models and describe the phenotypic characterization of the models.

2. Define the molecular analysis of the models, with m6A mapping, transcriptome, and translatome profiling.

3. Evaluation of the propensity of the cell models to undergo differentiation toward the neural cell lineages, by imposing environmental in vitro cues.

4. Use and develop investigational probes to selectively inhibit the YTHDF readers in cellulo and characterize the molecular mechanism behind.

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