{"624393":{"#nid":"624393","#data":{"type":"event","title":"PhD Defense by Evan Clayton","body":[{"value":"\u003Cp\u003EIn partial fulfillment of the requirements for the degree of\u0026nbsp;\u003C\/p\u003E\r\n\r\n\u003Cp\u003EDoctor of Philosophy in Bioinformatics\u003C\/p\u003E\r\n\r\n\u003Cp\u003Ein the School of Biological Sciences\u003C\/p\u003E\r\n\r\n\u003Cp\u003E\u0026nbsp;\u003C\/p\u003E\r\n\r\n\u003Cp\u003E\u003Cstrong\u003EEvan Clayton\u003C\/strong\u003E\u003C\/p\u003E\r\n\r\n\u003Cp\u003E\u0026nbsp;\u003C\/p\u003E\r\n\r\n\u003Cp\u003EDefends his thesis:\u003C\/p\u003E\r\n\r\n\u003Cp\u003E\u003Cstrong\u003EGlobal Dysregulation of Gene Expression and Tumorigenesis: Data Science for Cancer\u003C\/strong\u003E\u003C\/p\u003E\r\n\r\n\u003Cp\u003E\u0026nbsp;\u003C\/p\u003E\r\n\r\n\u003Cp\u003EThursday, August 22\u003Csup\u003End\u003C\/sup\u003E, 2019\u003C\/p\u003E\r\n\r\n\u003Cp\u003E1:00 PM Eastern Time\u003C\/p\u003E\r\n\r\n\u003Cp\u003EIBB Suddath Room 1128\u003C\/p\u003E\r\n\r\n\u003Cp\u003E\u0026nbsp;\u003C\/p\u003E\r\n\r\n\u003Cp\u003E\u003Cstrong\u003EThesis Advisor:\u003C\/strong\u003E\u003C\/p\u003E\r\n\r\n\u003Cp\u003EDr. John F. McDonald\u003C\/p\u003E\r\n\r\n\u003Cp\u003ESchool of Biological Sciences\u003C\/p\u003E\r\n\r\n\u003Cp\u003EGeorgia Institute of Technology\u003C\/p\u003E\r\n\r\n\u003Cp\u003E\u0026nbsp;\u003C\/p\u003E\r\n\r\n\u003Cp\u003E\u0026nbsp;\u003C\/p\u003E\r\n\r\n\u003Cp\u003E\u003Cstrong\u003ECo-Advisor:\u003C\/strong\u003E\u003C\/p\u003E\r\n\r\n\u003Cp\u003EDr. King Jordan\u003C\/p\u003E\r\n\r\n\u003Cp\u003ESchool of Biological Sciences\u003C\/p\u003E\r\n\r\n\u003Cp\u003EGeorgia Institute of Technology\u003C\/p\u003E\r\n\r\n\u003Cp\u003E\u0026nbsp;\u003C\/p\u003E\r\n\r\n\u003Cp\u003E\u003Cstrong\u003ECommittee Members:\u003C\/strong\u003E\u003C\/p\u003E\r\n\r\n\u003Cp\u003EDr. Soojin Yi\u003C\/p\u003E\r\n\r\n\u003Cp\u003ESchool of Biological Sciences\u003C\/p\u003E\r\n\r\n\u003Cp\u003EGeorgia Institute of Technology\u003C\/p\u003E\r\n\r\n\u003Cp\u003E\u0026nbsp;\u003C\/p\u003E\r\n\r\n\u003Cp\u003EDr. Jung H. Choi\u003C\/p\u003E\r\n\r\n\u003Cp\u003ESchool of Biological Sciences\u003C\/p\u003E\r\n\r\n\u003Cp\u003EGeorgia Institute of Technology\u003C\/p\u003E\r\n\r\n\u003Cp\u003E\u0026nbsp;\u003C\/p\u003E\r\n\r\n\u003Cp\u003EDr. Peng Qiu\u003C\/p\u003E\r\n\r\n\u003Cp\u003EDepartment of Biomedical Engineering\u003C\/p\u003E\r\n\r\n\u003Cp\u003EGeorgia Institute of Technology and Emory University\u003C\/p\u003E\r\n\r\n\u003Cp\u003E\u0026nbsp;\u003C\/p\u003E\r\n\r\n\u003Cp\u003E\u0026nbsp;\u003C\/p\u003E\r\n\r\n\u003Cp\u003E\u003Cstrong\u003EAbstract\u003C\/strong\u003E\u003C\/p\u003E\r\n\r\n\u003Cp\u003E\u0026nbsp;\u003C\/p\u003E\r\n\r\n\u003Cp\u003EDysregulation of gene expression is a hallmark of cancer.\u0026nbsp; Broadly speaking, my research is focused on the changes in gene expression that characterize the transition from normal to cancerous states, i.e. tumorigenesis.\u0026nbsp; To study such changes, I performed integrated analysis of next generation sequencing data for matched normal and primary tumor samples from hundreds of patients across numerous different cancer types.\u0026nbsp; By analyzing this sequencing data, I have been able to explore the global landscape of transcriptional reprogramming in cancer and discover how changes in the regulation of gene expression may be implicated in tumorigenesis.\u0026nbsp; My thesis is focused on four specific areas of transcriptional reprogramming in cancer: (1) changes in the expression and activity of transposable elements (TEs), (2) changes in alternative splicing induced by TEs, (3) allele-specific expression of tumor suppressor genes (TSGs), and (4) gene expression changes that are implicated in cancer drug response.\u003C\/p\u003E\r\n\r\n\u003Cp\u003ETEs are known to be uniformly overexpressed in cancer, suggesting a possible role for their activity in tumorigenesis.\u0026nbsp; I discovered a class of long interspersed nuclear elements (the LINE-1 family) with elevated levels of expression and activity in three different cancer types, and I showed examples where cancer-specific LINE-1 insertions disrupt enhancers, leading to the down-regulation of TSGs.\u003C\/p\u003E\r\n\r\n\u003Cp\u003ETEs are also implicated in the creation of novel splicing isoforms, and aberrant alternative splicing has been associated with tumorigenesis for a number of different cancers. Integrated analysis of genome sequence and transcriptome data revealed thousands of TE-generated alternative splice events genome-wide, including close to 5,000 events distributed among cancer associated genes. I explored the functional implications of specific cases of isoform switching, whereby TE-induced isoforms of cancer associated genes show elevated levels of relative expression in tumor samples.\u003C\/p\u003E\r\n\r\n\u003Cp\u003EA closer look at TSG expression in matched normal and tumor samples indicated that functionally important changes in patterns of allele-specific expression in individuals heterozygous for loss-of-function TSG alleles is a significant factor in cancer onset\/progression. These results identified a variety of molecular mechanisms that contribute to the observed changes in allele-specific expression patterns in cancer with allele-specific alternative splicing mediated by anti-sense RNA emerging as a predominant factor. Furthermore, analysis of the genomic variation for world-wide human populations demonstrates that loss-of-function TSG alleles are segregating at remarkedly high frequencies implying that a significant fraction of otherwise healthy individuals may be pre-disposed to developing cancer.\u003C\/p\u003E\r\n\r\n\u003Cp\u003EFor the final study of my thesis research, I applied the gene expression data from primary tumor samples to build predictive models of cancer drug response for two common chemotherapeutics: 5-Fluorouracil and Gemcitabine.\u0026nbsp; My gene expression based models predict whether patients will respond to individual therapies with up to 86% accuracy. The genes that I found to be most informative for predicting drug response were enriched in well-known cancer signaling pathways highlighting their potential significance in prognosis of chemotherapy.\u003C\/p\u003E\r\n\r\n\u003Cp\u003E\u0026nbsp;\u003C\/p\u003E\r\n","summary":null,"format":"limited_html"}],"field_subtitle":"","field_summary":"","field_summary_sentence":[{"value":"Global Dysregulation of Gene Expression and Tumorigenesis: Data Science for Cancer"}],"uid":"27707","created_gmt":"2019-08-13 12:15:05","changed_gmt":"2019-08-13 12:15:05","author":"Tatianna Richardson","boilerplate_text":"","field_publication":"","field_article_url":"","field_event_time":{"event_time_start":"2019-08-22T14:00:00-04:00","event_time_end":"2019-08-22T16:00:00-04:00","event_time_end_last":"2019-08-22T16:00:00-04:00","gmt_time_start":"2019-08-22 18:00:00","gmt_time_end":"2019-08-22 20:00:00","gmt_time_end_last":"2019-08-22 20:00:00","rrule":null,"timezone":"America\/New_York"},"extras":[],"groups":[{"id":"221981","name":"Graduate Studies"}],"categories":[],"keywords":[{"id":"100811","name":"Phd Defense"}],"core_research_areas":[],"news_room_topics":[],"event_categories":[{"id":"1788","name":"Other\/Miscellaneous"}],"invited_audience":[{"id":"78761","name":"Faculty\/Staff"},{"id":"78771","name":"Public"},{"id":"174045","name":"Graduate students"},{"id":"78751","name":"Undergraduate students"}],"affiliations":[],"classification":[],"areas_of_expertise":[],"news_and_recent_appearances":[],"phone":[],"contact":[],"email":[],"slides":[],"orientation":[],"userdata":""}}}