{"624975":{"#nid":"624975","#data":{"type":"event","title":"PhD Proposal by Catherine Demos","body":[{"value":"\u003Cp\u003E\u003Cstrong\u003ECatherine Demos\u0026nbsp;\u003C\/strong\u003E\u003C\/p\u003E\r\n\r\n\u003Cp\u003EBME PhD Proposal Presentation\u003C\/p\u003E\r\n\r\n\u003Cp\u003E\u0026nbsp;\u003C\/p\u003E\r\n\r\n\u003Cp\u003EDate: September 4, 2019\u003C\/p\u003E\r\n\r\n\u003Cp\u003ETime: 1 pm\u003C\/p\u003E\r\n\r\n\u003Cp\u003ELocation: HSRB E-182\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 Hanjoong Jo, Ph.D.\u003C\/p\u003E\r\n\r\n\u003Cp\u003E\u003Cstrong\u003EThesis Committee Members:\u003C\/strong\u003E\u003C\/p\u003E\r\n\r\n\u003Cp\u003EChangwon Park, Ph.D.\u003C\/p\u003E\r\n\r\n\u003Cp\u003EWilbur Lam, MD, Ph.D.\u003C\/p\u003E\r\n\r\n\u003Cp\u003EJames Dahlman, Ph.D.\u003C\/p\u003E\r\n\r\n\u003Cp\u003EYuhong Fan, Ph.D.\u003C\/p\u003E\r\n\r\n\u003Cp\u003E\u0026nbsp;\u003C\/p\u003E\r\n\r\n\u003Cp\u003ETitle: \u003Cem\u003ERole of novel flow sensitive transcription factor SIX2 in endothelial function and atherosclerosis\u003C\/em\u003E\u003C\/p\u003E\r\n\r\n\u003Cp\u003E\u0026nbsp;\u003C\/p\u003E\r\n\r\n\u003Cp\u003EAbstract:\u003C\/p\u003E\r\n\r\n\u003Cp\u003EAtherosclerosis, a chronic inflammatory disease of the arteries and the underlying cause of heart attacks, ischemic strokes, and peripheral artery disease, preferentially occurs in curved and branching regions of the vasculature where endothelial cells experience low-magnitude and oscillatory shear stress from disturbed blood flow (\u003Cem\u003Ed-flow\u003C\/em\u003E). Atherosclerosis rarely occurs in straight, unbranched regions of the vasculature where endothelial cells experience high-magnitude, unidirectional shear stress from stable blood flow (\u003Cem\u003Es-flow\u003C\/em\u003E). \u003Cem\u003ED-flow\u003C\/em\u003E induces pro-atherogenic endothelial responses, while \u003Cem\u003Es-flow\u003C\/em\u003E triggers atheroprotective changes driven by flow sensitive transcription factors (fTFs) in a process called endothelial reprogramming. Although there are many participating fTFs, the two most studied are KLF2 and KLF4 which are considered the master regulators of flow. However, KLF2\/4 together account for less than 65% of flow sensitive gene changes therefore we hypothesize that there are additional master regulator fTFs which warrant investigation.\u003C\/p\u003E\r\n\r\n\u003Cp\u003EThrough bioinformatics analysis, qPCR and immunostaining validation both \u003Cem\u003Ein vivo\u003C\/em\u003E and \u003Cem\u003Ein vitro\u003C\/em\u003E, we have identified the novel fTF SIX2 and propose that this transcription factor is an additional master regulator of flow. Early studies on SIX2 have focused on nephron progenitor cells and only recently has SIX2 been shown to have an effect in additional cell types. Reported functions of SIX2 include repressing cell reprogramming, maintaining stem-like qualities, and preventing epithelial-to-mesenchymal transition. This is a highly similar pathway to endothelial-to-mesenchymal transition (EndMT), an endothelial function which has long been studied as a driver of atherosclerotic progression. We have found SIX2 to be upregulated by \u003Cem\u003Es-flow\u003C\/em\u003E and lost in \u003Cem\u003Ed-flow\u003C\/em\u003E as early as 12 hours post-surgery in our acute model of induced \u003Cem\u003Ed-flow\u003C\/em\u003E, indicating it is an early responder to shear stress and potentially plays a key role in preventing endothelial inflammation. Endothelial inflammation is also one of the initial changes observed under \u003Cem\u003Ed-flow\u003C\/em\u003E, and a major factor in atherosclerosis.\u003C\/p\u003E\r\n\r\n\u003Cp\u003ETaking these data together, we hypothesize that SIX2 is a master regulator of endothelial response to flow and a key factor in preventing atherosclerotic endothelial reprogramming, especially EndMT and inflammation. We will investigate this hypothesis in three aims: 1) determine the role of SIX2 in flow-dependent endothelial reprogramming, 2) identify flow-sensitive target genes of SIX2 and determine the mechanisms by which SIX2 regulates flow-dependent endothelial reprogramming, and 3) determine the effect of SIX2-deficiency in atherosclerosis \u003Cem\u003Ein vivo\u003C\/em\u003E. These studies will reveal the novel role of SIX2 in flow-dependent regulation of its target genes, endothelial function, and atherosclerosis. Our work may also reveal potential therapeutic targets of atherosclerosis.\u003C\/p\u003E\r\n","summary":null,"format":"limited_html"}],"field_subtitle":"","field_summary":"","field_summary_sentence":[{"value":"Role of novel flow sensitive transcription factor SIX2 in endothelial function and atherosclerosis"}],"uid":"27707","created_gmt":"2019-08-22 13:21:38","changed_gmt":"2019-08-22 13:21:38","author":"Tatianna Richardson","boilerplate_text":"","field_publication":"","field_article_url":"","field_event_time":{"event_time_start":"2019-09-04T14:00:00-04:00","event_time_end":"2019-09-04T16:00:00-04:00","event_time_end_last":"2019-09-04T16:00:00-04:00","gmt_time_start":"2019-09-04 18:00:00","gmt_time_end":"2019-09-04 20:00:00","gmt_time_end_last":"2019-09-04 20:00:00","rrule":null,"timezone":"America\/New_York"},"extras":[],"groups":[{"id":"221981","name":"Graduate Studies"}],"categories":[],"keywords":[{"id":"102851","name":"Phd proposal"}],"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":""}}}