Gene Expression Regulation
Gene Expression Regulation
Our research interest is focused on the epigenetic and transcriptional regulation of gene expression in normal physiology and in disease. We study human diseases caused by aberrant gene expression and evaluate the therapeutic relevance of our findings using cellular and animal models.
Research activity
We are particularly interested in the regulation of muscle- and B-cell differentiation, and the associated diseases using FSHD muscular dystrophy and acute lymphoblastic leukemia, respectively, as paradigms.
FSHD is the most prevalent neuromuscular disease affecting males and females of all ages. The disease is caused by chromatin relaxation leading to inappropriate gain of expression of the double homeobox transcription factor DUX4, which is highly toxic to skeletal muscle leading to disease.
B cell acute lymphoblastic leukemia (B-ALL) is the most common pediatric cancer and the major cause of cancer-related death among children and young adults. DUX4 translocations have been reported in up to 7% of B-ALL patients and define a new B-ALL subtype. In these patients, a rearranged and oncogenic version of DUX4 (DUX4-r) is the leukemia driver.
To perform our studies, we combine biochemistry, cell biology and molecular biology tools together with functional and genome wide approaches in order to understand the mechanisms controlling DUX4 and DUX4-r expression and activity. We evaluate the therapeutic relevance of our findings using cellular and animal models of the diseases.
