Introduction

DNA methylation-related genes are among the most frequently mutated in blood malignancies. Traditionally, studies aimed at understanding the effect of aberrant DNA methylation in cancer patients have focused on gene promoters. However, recent findings focus on enhancers as the most important regions in dynamic DNA methylation studies. We aim to understand how aberrant DNA methylation dynamics impact on the chromatin structure at enhancers during blood cancer onset and progression.

Our Research

We study how aberrant DNA methylation at distal gene regulatory regions poisons the chromatin to trigger corrupted gene expression signatures in cells, thus eventually leading to the onset and progression of haematological neoplasms. This line of research has implications for a broad spectrum of patients suffering from blood diseases sharing an abnormal genome-wide DNA methylation landscape.

Our Goals

We aim to unravel the different layers of intricated epigenetic information that specify which subsets of genes are expressed in every one of the cells of the haematopoietic system, thereby defining their cellular identity. We hope to apply this knowledge to better understand how and when deleterious transcriptional programmes leading to cellular transformation are activated, thus leading to the discovery of new treatments that will potentially end up in improving the quality of life of patients suffering from a wide range of blood diseases.

Our Challenges

There is an urgent need for novel therapies for acute myeloid leukemia, since barely any drugs introduced in the last decades have increased the overall survival its patients. Hence, our research aims to shed light on the following questions:

1. What is the interplay between DNA (hydroxy)methylation and chromatin dynamics at distal gene regulatory regions during haematopoietic cell fate decisions?

2. What are the molecular mechanisms underlying the role of TET2 in the epigenetic control of the chromatin at distal gene regulatory regions during leukaemia onset and progression?

3. What is the role of mRNA methylation-mediated post-transcriptional control in myeloid cell differentiation?