{"620316":{"#nid":"620316","#data":{"type":"event","title":"Phd Proposal by Kalina Paunovska","body":[{"value":"\u003Cp\u003E\u003Cstrong\u003EKalina Paunovska\u003C\/strong\u003E\u003C\/p\u003E\r\n\r\n\u003Cp\u003E\u003Cstrong\u003EPhD Proposal Presentation\u003C\/strong\u003E\u003C\/p\u003E\r\n\r\n\u003Cp\u003E\u0026nbsp;\u003C\/p\u003E\r\n\r\n\u003Cp\u003E\u003Cstrong\u003EDate:\u0026nbsp;\u003C\/strong\u003EApril 25th, 2019\u003C\/p\u003E\r\n\r\n\u003Cp\u003E\u003Cstrong\u003ETime:\u0026nbsp;\u003C\/strong\u003E1:00 PM\u003C\/p\u003E\r\n\r\n\u003Cp\u003E\u003Cstrong\u003ELocation:\u0026nbsp;\u003C\/strong\u003EMcIntire Conference Room, 3rd floor of Whitaker\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\u003E\u0026nbsp;\u003C\/p\u003E\r\n\r\n\u003Cp\u003EJames E. Dahlman, Ph.D. (Advisor)\u003C\/p\u003E\r\n\r\n\u003Cp\u003EWallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University\u003C\/p\u003E\r\n\r\n\u003Cp\u003E\u0026nbsp;\u003C\/p\u003E\r\n\r\n\u003Cp\u003EAndres Garcia, Ph.D.\u003C\/p\u003E\r\n\r\n\u003Cp\u003EWallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University\u003C\/p\u003E\r\n\r\n\u003Cp\u003E\u0026nbsp;\u003C\/p\u003E\r\n\r\n\u003Cp\u003EPhilip J. Santangelo, Ph.D.\u003C\/p\u003E\r\n\r\n\u003Cp\u003EWallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University\u003C\/p\u003E\r\n\r\n\u003Cp\u003E\u0026nbsp;\u003C\/p\u003E\r\n\r\n\u003Cp\u003EEdward Botchwey, Ph.D.\u003C\/p\u003E\r\n\r\n\u003Cp\u003EWallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University\u003C\/p\u003E\r\n\r\n\u003Cp\u003E\u0026nbsp;\u003C\/p\u003E\r\n\r\n\u003Cp\u003EJulie Champion, Ph.D.\u003C\/p\u003E\r\n\r\n\u003Cp\u003EDepartment of Chemical and Biomolecular Engineering, Georgia Institute of Technology\u003C\/p\u003E\r\n\r\n\u003Cp\u003E\u0026nbsp;\u003C\/p\u003E\r\n\r\n\u003Cp\u003E\u003Cstrong\u003ETitle:\u0026nbsp;\u003C\/strong\u003EAn investigation of parameters that influence non-hepatocyte RNA delivery\u0026nbsp;\u003Cem\u003Ein vivo\u003C\/em\u003E\u003C\/p\u003E\r\n\r\n\u003Cp\u003E\u0026nbsp;\u003C\/p\u003E\r\n\r\n\u003Cp\u003E\u003Cstrong\u003EAbstract:\u0026nbsp;\u003C\/strong\u003ELipid nanoparticle (LNP)-mediated nucleic acid delivery can regulate the expression of any gene, making this approach a promising way to treat disease. However, clinically relevant delivery of RNA therapies to non-hepatocytes\u0026nbsp;\u003Cem\u003Ein vivo\u0026nbsp;\u003C\/em\u003Eremains challenging.Most LNPs are created by mixing an ionizable lipid with PEG, a phospholipid, and cholesterol, making it possible to create thousands of chemically distinct LNPs. These nanoparticles are typically screened\u0026nbsp;\u003Cem\u003Ein vitro\u0026nbsp;\u003C\/em\u003Ein easily expandable cell lines, yet these cell culture conditions are not representative of\u0026nbsp;\u003Cem\u003Ein vivo\u0026nbsp;\u003C\/em\u003Etissue microenvironments. LNPs that deliver their payload (e.g. DNA, RNA) successfully\u0026nbsp;\u003Cem\u003Ein vitro\u0026nbsp;\u003C\/em\u003Eare then validated\u0026nbsp;\u003Cem\u003Ein vivo\u003C\/em\u003E.\u0026nbsp;This leads to a small number of viable candidates as particles that tend to work\u0026nbsp;\u003Cem\u003Ein vitro\u0026nbsp;\u003C\/em\u003Edo not necessarily work\u0026nbsp;\u003Cem\u003Ein vivo\u003C\/em\u003E.The objective of this\u0026nbsp;proposal\u0026nbsp;is to use high-throughput DNA barcoding to ask fundamental questions about\u0026nbsp;\u003Cem\u003Ein vivo\u0026nbsp;\u003C\/em\u003Edrug delivery. In particular, we will make 4 significant contributions to the field of nucleic acid delivery. First, we will test whether\u0026nbsp;\u003Cem\u003Ein vitro\u0026nbsp;\u003C\/em\u003ELNP delivery is predictive of\u0026nbsp;\u003Cem\u003Ein vivo\u003C\/em\u003ELNP delivery. We will test this effect in many cell types (i.e. endothelial, macrophage) from many tissues (i.e. heart, lung, bone marrow). Second, we will investigate whether cholesterol structure \u0026ndash; a previously unperturbed LNP component \u0026ndash; can impact LNP delivery\u0026nbsp;\u003Cem\u003Ein vivo\u003C\/em\u003E. Cholesterol variants are naturally trafficked in lipoproteins (i.e. LDL, VLDL) suggesting that LNP targeting can be tuned by using naturally- or synthetically-derived cholesterol variants. Third, we will identify LNPs that deliver RNA to non-hepatocytes more efficiently than to hepatocytes. Fourth, we will develop and optimize a novel functional LNP screening platform that is independent of the cell type being targeted or the mouse model being used. This will allow us to perform screens and LNP validation\u0026nbsp;studies\u0026nbsp;in transgenic mice so that we can understand the impact of particular genes on LNP trafficking and nucleic acid delivery. Taken together, this work will enable both the understanding and optimization of factors that influence non-hepatocyte RNA delivery\u0026nbsp;\u003Cem\u003Ein vivo\u003C\/em\u003E.\u0026nbsp;\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":"An investigation of parameters that influence non-hepatocyte RNA delivery in vivo"}],"uid":"27707","created_gmt":"2019-04-11 14:23:30","changed_gmt":"2019-04-11 14:23:30","author":"Tatianna Richardson","boilerplate_text":"","field_publication":"","field_article_url":"","field_event_time":{"event_time_start":"2019-04-25T14:00:00-04:00","event_time_end":"2019-04-25T16:00:00-04:00","event_time_end_last":"2019-04-25T16:00:00-04:00","gmt_time_start":"2019-04-25 18:00:00","gmt_time_end":"2019-04-25 20:00:00","gmt_time_end_last":"2019-04-25 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":"78751","name":"Undergraduate students"}],"affiliations":[],"classification":[],"areas_of_expertise":[],"news_and_recent_appearances":[],"phone":[],"contact":[],"email":[],"slides":[],"orientation":[],"userdata":""}}}