Angela Mo Thesis Defense

In partial fulfillment of the requirements for the degree of Doctor of Philosophy in Bioinformatics in the School of Biological Sciences Angela Mo Defends her thesis:Genomic and Transcriptomic Characterization of Inflammatory Bowel Disease Friday, April 2, 2021 2:00 PM Eastern Timehttps://bluejeans.com/771161957 Thesis Advisor: Dr. Greg Gibson School of Biological Sciences Georgia Institute of Technology Committee Members: Dr. Joseph Lachance School of Biological Sciences Georgia Institute of Technology   Dr. I. King Jordan School of Biological Sciences Georgia Institute of Technology Dr. Peng Qiu Department of Biomedical Engineering Georgia Institute of Technology Dr. Subra Kugathasan Department of Pediatrics and Human Genetics Emory University Abstract: Inflammatory bowel disease (IBD) is a chronic idiopathic disorder resulting in the inflammation of the gastrointestinal tract, which encapsulates both Crohn's disease (CD) and ulcerative colitis (UC). There is strong evidence of familial aggregation of IBD, and more than 200 genetic variants have been identified as associated with IBD . Currently, more than 1.5 million individuals in the United States suffer from IBD, with prevalence of the disease on the rise, particularly in minority populations. The primary question driving this thesis is whether genomic and transcriptomic profiling have the potential to direct personalized therapeutic interventions for IBD patients. Prediction of disease course is especially relevant in IBD, because early, appropriate introduction of anti-TNFα therapy can slow the progression of the disease in patients who would otherwise experience severe flares, bowel penetration, or require invasive surgeries. Conversely, early prediction can also identify patients who are not expected to progress and thus help to avoid unnecessary, harmful, and costly therapy with biologics. Our prior studies have demonstrated that transcriptomic data can be used to identify patients who are likely to progress from B1 stable CD to B3 penetrating CD, and that gene expression can also be linked to GWAS via Transcriptional Risk Scores (TRS). In this thesis, I first describe a comparative analysis of gene expression and eQTL in IBD and juvenile idiopathic arthritis, another clinically heterogeneous immune-related disorder. Next, I examine the influence of African ancestry proportion on gene expression in the ileum of Crohn's disease patients. I then discuss the utility of gene expression at time of disease diagnosis to predict risk of progression to colectomy in an inception cohort of pediatric ulcerative colitis patients. Finally, I present an exploration of cell type composition of ileal epithelial cells at single-cell resolution in healthy, treatment-naïve, and treated Crohn's disease. I conclude with a summary of the progress achieved and challenges to be overcome for the successful application of genomics for precision medicine in IBD and beyond.

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Angela Mo, Bioinformatics PhD
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Angela Mo, Bioinformatics PhD

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