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PhD Exit Seminar -Wilfred Carlo de Vega -Wednesday, November 22, 2017
November 22 @ 2:10 pm - 3:00 pm
PhD Exit Seminar
Wednesday, November 22, 2017 at 2:10 pm, SW 403 – University of Toronto at Scarborough
Wilfred Carlo de Vega (McGowan Lab)
“DNA Methylation Modifications Associated with Glucocorticoid Sensitivity and Clinical Subtypes of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome”
Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a complex chronic disease with an unknown etiology that is primarily characterized by the presence of a highly debilitating fatigue that fails to resolve after sufficient rest. Additionally, patients must present other nonspecific symptoms relating to pain, unrefreshing sleep, cognitive impairment, and autonomic dysregulation in order to be diagnosed with ME/CFS, resulting in a population with highly heterogeneous symptom profiles. Previous research has consistently observed long-lasting changes in the immune system and hypothalamic-pituitary-adrenal (HPA) axis, a neuroendocrine system that regulates stress response. As a prototypical medically unexplained disease, environmental factors are believed to play a major role in the onset and manifestation of ME/CFS symptoms. These enduring differences may be partly explained through epigenetic modifications, referring to heritable gene expression alterations in the absence of mutations, which are known to reflect environmental, genetic, and stochastic influences on gene expression. This thesis explored the epigenetic modifications associated with the immune and neuroendocrine differences in ME/CFS. Specifically, DNA methylation across the genome was examined in peripheral blood mononuclear cells of ME/CFS patients, and immune response was tested by measuring in vitro sensitivity to glucocorticoids, a class of hormones that serve as an HPA axis effector. Differential methylation in ME/CFS was significantly enriched in immune response and cellular signaling genes, and was localized to 4,699 sites, which may serve as potential biomarkers. Two ME/CFS immune subtypes were observed according to glucocorticoid sensitivity. Integration of methylation and clinical data via machine learning discovered 4 clinical subtypes that were differentiated by T cell response genes, physical functioning, and post-exertional malaise. These results suggest that DNA methylation modifications are a feature of ME/CFS pathology. The identified potential biomarkers and clinical subtypes may be implemented in future work to better understand and clarify the biological differences related to specific ME/CFS symptoms.