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Research Interests
The Mandel Lab research is focused on understanding how neuronal cell identity is established and maintained. Unexpectedly, the lab discovered that this is achieved primarily through a repressor mechanism. At the heart of this mechanism lies the DNA-binding protein, REST. Together with its interaction partners, REST controls the epigenetic status of neuronal gene chromatin. Knowledge of this mechanism provides a window into the molecular events governing nervous system formation.
The lab is exploiting embryonic stem cell differentiation and knock out animals to understand how the repressor complex is regulated during normal development. Using a novel strategy for characterizing transcription factor binding sites, we have elucidated the REST genetic network and are studying how this network, and its associated chromatin signature, directs normal neuronal differentiation and contributes to autism spectrum disorders. Most recently, we have extended our studies to explore neuronal:glial interactions. We have uncovered a potential role for glia in inducing neuronal dysfunction in Rett Syndrome, one of the most common causes of mental retardation in young girls. Our goal is to identify how the glial genes or proteins cause the underlying neuronal pathology.
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