William Renehan, PhD
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Affiliation(s):
University of Rhode Island
Areas of Interest:
epigenetic, microRNAs/miRNAs, Alzheimer disease
Biography & Research:
My laboratory studies the relationship between the epigenome (factors that influence gene expression without changing the genetic code) and the genes that encode neurotoxic proteins. There is substantial evidence, much of it obtained at URI by my collaborator Nasser Zawia, that early-life exposure to environmental toxins produces changes to the neural epigenome. We believe that these changes lead ultimately to the cellular damage and neuronal death that occur in neurodegenerative disorders such as Alzheimer’s disease (AD) and Parkinson’s disease. I am most interested in the effects of environmental toxins on microRNA (miRNA). MiRNA inhibit gene expression by promoting the degradation of messenger RNA or suppressing expression via translational inhibition. Our data suggest that toxin-induced changes in the levels of select miRNA may be involved in the pathogenesis of late-onset Alzheimer’s disease (LOAD). We believe that exposure to environmental toxins in early life stimulates increased expression of miRNA that bind to the messenger RNA for neurotoxic proteins and certain epigenetic mediators. Over time, stochastic changes (possibly induced by oxidative damage or exposure to additional toxins) impair the ability of these miRNA to regulate the expression of cytotoxic proteins, allowing their increased expression and associated neuropathology. We are employing a variety of genomic and epigenomic profiling techniques to quantify changes in neuronal miRNA in animal models of AD. Our ultimate goal is to develop protocols that will allow us to manipulate the expression of these miRNA and thus offer novel strategies for the prevention of AD and other neurodegenerative diseases.
