Early life experience not only shapes our brains and behaviors but impacts our risk for developing disease throughout our life. But how do our genes and environment combine to shape our developing brains? Epigenetic mechanisms that control the expression of genes without altering the underlying genetic code allow for cellular adaptation to a changing environment. These fundamental mechanisms control cellular differentiation, producing the vast diversity of cells in the body. They are also likely disrupted in many neurodevelopmental and neuropsychiatric disorders.
The cause of neurodevelopmental disorders is complex and involves both genetic and environmental risk factors. A multitude of early-life environmental exposures and maternal health conditions increase the risk of neurodevelopmental disorders, including maternal immune activation and pollutant exposure during pregnancy. Disruption of epigenetic processes regulating brain developmental has been proposed as a potential mechanism linking environmental and genetic risk.
Why is this important?
Neurodevelopmental disorders are one of the leading causes of lifelong disability in Canada and their rate of diagnosis is increasing. They place a heavy burden on our healthcare and education systems, social services, and families. Combined with the rising diagnosis rates and limited treatments currently available, there is a great need to accelerate the discovery and development of novel therapeutics.
Autism Spectrum Disorder (ASD), one type of neurodevelopmental disorder, is a heterogenous disorder characterized by impaired social communication and language accompanied by increased repetitive behaviors and restricted interests. The disorder also includes many co-morbidities including disruption of the immune system. The immune and nervous systems interact during normal brain development to shape neuronal connections, neuronal numbers and cell-to-cell communication. But how these two systems precisely coordinate their interactions during brain development is not well understood.
The Ciernia laboratory combines experimental and computational approaches to understand how epigenetic mechanisms regulate gene expression across our lifespan. The lab specifically focuses on mechanisms of epigenetic regulation in multiple brain cell populations across normal brain and immune system development and in rodent models of neurodevelopmental disorders. We test novel hypotheses linking genetic and environmental risk factors to altered patterns of gene expression, epigenomic regulatory pathways, cellular function and animal behavior. Findings from our research will increase our understanding of the basic mechanisms regulating gene expression in the brain and form the basis for future development of novel immune targeted therapeutics for neurodevelopmental disorders such as ASD.