Key Objectives & Expected Results
Brief overview of this project’s objectives and expected results:
- To uncover pathway activities in clinical ER- positive tumor samples via systematic screening with Reverse Phase Protein Array (RPPA) technology towards stratification of molecular subtypes
- To determine epigenetic/gene expression profiles (Illumina 450k and gene expression arrays/RNA-seq).
- To identify gene mutations (DNA sequencing) in the same patients.
- To correlate patients’ pathway activation, epigenetic/expression and mutation profiles with clinical annotation (time to relapse/time to recurrence)
- To correlate clinical pathway activation profiles with equivalent profiles in resistance-induced cell line models.
- Quantitative time-resolved perturbation data by in vitro experimentation that will serve as a basis to model drug response mechanisms.
- Insights which signalling pathways are affected in epigenetically subclassified patients
- Prediction of mechanisms leading to drug resistance, metastasis formation
- Experimental validation of mechanisms by means of perturbation experiments (RNAi, CRISPR, etc.)
Host training: ChIP-seq, gene expression (Ilmunina), Bisufite-450k, Patient tissue, sera, cell lysates, RPPA pathway activation screening, next generation sequencing
Planned secondment(s): Epiontis: DNA methylation kit development (M29-30), UvA: Bioinformatics/modelling (M12-13), ), MTA-SZBK: DNA methylation interference tools (M19)