Gene expression regulation in the brain in health and disease

Host: Thomas Preiss

Abstract

Behavioural and neuropsychiatric traits are genetically complex and associated primarily with non-coding variants located in regulatory regions that control gene expression. Thousands of candidate distal regulatory regions have been mapped based on biochemical properties such as open chromatin state and chromatin post-translational modifications. However, the functional validation of these candidate regions and linking enhancers to their target genes remains challenging. This talk will discuss our recent high-throughput CRISPRi screen of enhancers in human glial cells, and novel evidence for the role ZMYND8, a transcriptional regulator that controls enhancer activity, in intellectual disability. 

Biography

Broadly, my research interests are in the area of molecular genetic mechanisms underlying human brain disorders. My PhD work demonstrated that unstable DNA repeats block replication fork progression in bacteria, yeast and mammalian cells by forming DNA-hairpins on the lagging strand (Voineagu et al. PNAS 2008), and investigated for the first time the cellular checkpoint responses to replication fork arrest at CGG repeats. This work led to a novel model of chromosomal fragility at CGG repeat sequences (Voineagu et al. Nature Struct. Mol. Biol 2009). For postdoctoral research, I joined the Neurogenetics Department at UCLA, to investigate the molecular mechanisms of autism and intellectual disability, using transcriptome methods.  My postdoctoral work led to the identification of a novel gene implicated in X-linked intellectual disability (Voineagu et al., Mol. Psychiatry 2011) and the characterisation of shared molecular pathways in autism post-mortem brain tissue (Voineagu et al. Nature 2011).Currently, my group's research concentrates on the molecular genetic mechanisms underlying normal brain function and their perturbation in neurodevelopmental disorders, using a combination of functional genomic studies in human brain tissue and neuronal cell culture systems.