We are going to perform serial high-throughput RNA sequencing on sorted white blood cell subtypes from buffy coats issued from healthy donors. This will allow us to define the required sequencing depth to obtain informative expression signatures across individuals. In a second phase, we are going to confront the data issued from bulk and single-cell RNA sequencing to ascertain the cell-type origin of the detected signal. In parallel, we are building a collaboration with university hospitals to explore the ability of high-throughput RNA sequencing to serve as a disease monitoring tool in stem cell transplant recipients at risk of graft-versus host disease (GVHD).
Our aim is also to characterize epigenetic regulatory networks used by TFs displaying TEs binding patterns throughout the human genome and more specifically oncogenic TFs. We are exploring oncogenic TF-TEs associations by challenging putative regulatory systems, through gene editing and transduction experiments on lymphoblastoid, leukemia and lymphoma cell-lines.
Minimal residual disease detection (MRD) methods and cancer patient’s stratification according to epigenetic profiling, going beyond current histopathological classifications, are major goals of modern personalized oncology. DNA next-generation sequencing (NGS) and RT-qPCR methods are implemented in the clinic and proved to have a positive impact on early detection of hematological malignancies.
In addition, the identification of disease regulatory networks and oncogenic drivers will enrich the repertoire of therapeutic targets and cancer knowledge. Malignancies are regulated by complex transcriptional networks, driven by oncogenic TFs interacting at multiple cis-acting genomic sequences. A fraction of TE integrants serve as regulatory elements of nearby genes, thus shaping the transcriptomic profile of cancer cells but also their normal physiological counterparts in a tissue-specific manner.
