Developmental Epigenomics

DNA methylation and histone modifications are two major mediators of epigenetic processes in mammals and the question that inspires us, is to understand how mutations in factors that read, write or erase epigenetic marks lead to human disease, with the ultimate aim to develop targeted epigenetic therapies.

Towards this goal, we are making use of a set of models that emerged from a large chemical mutagenesis screen for epigenetic regulators in the mouse. This screen identified about 30 genes, Modifiers of murine metastable epialleles Dominant (MommeD), with roles in DNA methylation, histone modification and chromatin remodelling pathways. Intriguingly, many of these factors have also been identified as risk factors for human disease. With this knowledge, we are selecting key factors as entry points into understanding their functions throughout normal development and in disease. We employ discovery-driven (epi)genomic approaches to expose epigenetic dysregulation caused by disruption of our genes of interest in mammalian (stem) cell model systems and/or patient-derived cells. We then use hypothesis-driven genetics, biochemistry, molecular biology and Crispr/Cas9-mediated (epi)genome-editing approaches to systematically unravel the underlying molecular processes.

For instance, in the context of Immunodeficiency, Centromeric instability, Facial anomalies (ICF) syndrome, we aim to elucidate how mutations in four different genes can lead to a primary immunodeficiency characterized by DNA hypomethylation of repetitive DNA. We are also investigating how epigenetic factors that read, write, or erase chromatin marks contribute to immune cell development and function. In the area of epigenetic inheritance we aim to understand how aberrant epigenetic state of the gametes can influence offspring phenotype.

If you are interested in joining our research group please consider the following options:

Open and funded PhD student/Postdoc positions will be advertised on the LUMC website and internationally.

Postdoctoral fellows: Applications from postdoctoral fellows with a strong background in epigenetics and gene regulation, computational biology, or biochemistry who are willing to apply for competitive grants are strongly encouraged.

Master/Bachelor students: Internship positions become available on a regular basis. Please contact us directly.

Dr. Lucia Clemens-Daxinger        
Principal Investigator / Associate Professor

Jihed Chouaref                              
Researcher

Serkan Dogan
Researcher

Veronica Della Chiara
PhD student

Maja Vukic                                     
PhD student

Fallon T. Ratner                                 
Student-assistant

Cor Breukel                                     
Research technician

Kelly K.D. Vonk                              
Research technician