Diseases of the nervous system are clinically, neuropathologically and genetically heterogeneous and complex conditions, in which dysfunction and/or death of selective neuronal populations are common and prominent disease features. Aberrant changes in gene function are involved in a wide spectrum of neurodegenerative and neuropsychiatric pathologies. Most of the attention over the past decades have focused on changes in gene sequence as a cause of gene dysfunction, resulting in discoveries of gene mutations that underlie the causes of some of these conditions such as Huntingtin gene mutation in Huntington’s disease and C9orf72 gene mutation in Frontotemporal Dementia/Amyotrophic Lateral Sclerosis disease spectrum (FTD/ALS). However, gene sequence alterations explain only a small fraction of the cases leaving vast majority of the brain disorders still etiologically unexplained. Even in the diseases, where clear genetic links were established, large patient-to-patient variations in the age of onset, disease progression and severity and neuropathological features point towards presence of additional disease mechanisms. In this context, especially considering their potent therapeutic effects in pre-clinical studies, epigenetic mechanisms, that are key to mediating gene-environment interactions, hold unprecedented potentials for understanding and treating brain diseases, for which the existing treatment options are largely palliative at the present time.
Our lab aims at understanding the mechanisms that underlie aberrant gene expression and epigenetic dysregulation in neurodegenerative and neuropsychiatric conditions with a specific focus on identifying new therapeutic targets. For linking gene expression and epigenetic changes to neuronal dysfunction and disease phenotypes, lab members apply a combination of genome-wide DNA sequencing technologies with mechanistic, functional and behavioural approaches to in vitro and mouse models of disease. As part of the NeuroCure research cluster, Einstein Center for Neurosciences and the Neuropsychiatry Department of Charite Medical School located in central Berlin, the ultimate goal of our research programs is the translation of pre-clinical findings to initiate clinical studies for development of effective therapies for patients.