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Epigenetics and Neural Plasticity Laboratory

The Neural Plasticity Laboratory investigates gene-environment interactions and experience-dependent plasticity in the healthy and diseased brain.

Our research includes using a model of Huntington’s disease (HD), a tandem repeat disorder, where we are following up our discoveries regarding the beneficial effects of environmental enrichment (enhanced cognitive stimulation and physical activity) and exercise, as well as depression and dementia-like symptoms associated with abnormalities of brain plasticity.  Furthermore, we recently discovered that chronic stress can accelerate onset of HD, and are investigating these neurotoxic effects of stress in HD and other brain disorders.

Many neurological and psychiatric disorders have their origins in abnormal maturation of the brain, including the billions of neurons exquisitely connected by trillions of synapses. We are also investigating how genetic and environmental factors combine to cause specific disorders of brain development and cognition, including schizophrenia and autism spectrum disorders (ASD).  We are interested in the mechanisms whereby specific genes regulate maturation of the brain and are dynamically regulated by interaction with the environment in conditions like ASD and schizophrenia. 

Our research links data at behavioural and cognitive levels to underlying cellular and molecular mechanisms.  We use a variety of behavioural tools, including automated touchscreen testing of cognition and high-throughput data analysis of vocalization and communication, that are directly translatable to clinical tests.  We are establishing the extent to which experience-dependent plasticity, including adult neurogenesis and synaptic plasticity, can modulate these behavioural and cognitive endophenotypes, in models with targeted genome editing.  This cellular level of understanding is linked, in turn, to molecular mechanisms, including epigenetics, transcriptomics and proteomics.

Based on this research, and the identification of key target molecules, we are also exploring the concept of ‘enviromimetics’, therapeutics that mimic or enhance the beneficial effects of cognitive stimulation and physical exercise.  One goal is to develop such therapeutic agents to help reduce the personal and societal burdens of devastating brain disorders such as schizophrenia, HD and dementia.

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