{"342641":{"#nid":"342641","#data":{"type":"event","title":"PhD Defense by Patricia M. Pacheco","body":[{"value":"\u003Cp\u003E\u003Cstrong\u003EPatricia M. Pacheco\u003C\/strong\u003E\u003Cbr \/\u003EBioE Ph.D. Dissertation Defense\u003Cbr \/\u003EDate:\u0026nbsp;November 10, 2014\u003Cbr \/\u003ETime: 9:00am\u003Cbr \/\u003ELocation: Marcus Nanotechnology Bldg 1117\u003Cbr \/\u003E\u003Cbr \/\u003EAdvisor:\u003Cbr \/\u003E\u003Cbr \/\u003ETodd Sulchek, Ph.D., Mechanical Engineering, Georgia Institute of Technology\u003Cbr \/\u003E\u003Cbr \/\u003ECommittee:\u003Cbr \/\u003EJulia Babensee, Ph.D., Biomedical Engineering, Georgia Institute of\u0026nbsp;\u003Cbr \/\u003ETechnology\u003Cbr \/\u003EJulie Champion, Ph.D., Chemical and Biomolecular Engineering, Georgia\u0026nbsp;\u003Cbr \/\u003EInstitute of Technology\u003Cbr \/\u003EAndr\u00e9s Garc\u00eda, Ph.D., Mechanical Engineering, Georgia Institute of\u0026nbsp;\u003Cbr \/\u003ETechnology\u003Cbr \/\u003EDavid M. White, D.V.M., Ph.D., DACVM, United States Department of\u0026nbsp;\u003Cbr \/\u003EAgriculture\u003Cbr \/\u003E\u003Cbr \/\u003E\u003Cstrong\u003EFc Coated Micro\/nanoparticles for Humoral Immune System Modulation\u003C\/strong\u003E\u003Cbr \/\u003E\u003Cbr \/\u003EThe body\u2019s humoral immune response plays a larger role beyond screening for\u0026nbsp;\u003Cbr \/\u003Einvading pathogens as it is also vital for tissue regeneration, drug\u0026nbsp;\u003Cbr \/\u003Edelivery, and vaccine processing. The immune system operates within a\u0026nbsp;\u003Cbr \/\u003Esophisticated feedback loops, and as such, reagents which may alter it in a\u0026nbsp;\u003Cbr \/\u003Etunable manner offer promise to study the immune system as well as engineer\u0026nbsp;\u003Cbr \/\u003Especific responses for therapeutic effect. While a strong initial input can\u0026nbsp;\u003Cbr \/\u003Esway the response to one of two extremes (pro- or anti-inflammatory), an\u0026nbsp;\u003Cbr \/\u003Eextreme response is not always required or desired in the case of\u0026nbsp;\u003Cbr \/\u003Eimmunocompromised patients. Therefore, we set out to derive a novel\u0026nbsp;\u003Cbr \/\u003Ebiomaterials platform to alter the immune response in a tunable manner.\u0026nbsp;\u003Cbr \/\u003EAntibodies are not only the workhorses of the adaptive immune response but\u0026nbsp;\u003Cbr \/\u003Eare also powerful immunomodulators through their Fc (constant fragment)\u0026nbsp;\u003Cbr \/\u003Eregions. By coating microparticles with Fc ligands in variable surface\u0026nbsp;\u003Cbr \/\u003Edensities, we were able to utilize the sensitivity of multivalent signaling\u0026nbsp;\u003Cbr \/\u003Eto tune the response of the immune response. Microparticle size was also\u0026nbsp;\u003Cbr \/\u003Evaried to decouple the effects of physical versus biochemical signaling.\u003Cbr \/\u003E\u003Cbr \/\u003EThe goal of this thesis was to analyze the effects of Fc coated particles on\u0026nbsp;\u003Cbr \/\u003Etwo major components of the humoral immune responses: macrophages and the\u0026nbsp;\u003Cbr \/\u003Ecomplement system. We first looked at the mechanical response of macrophages\u0026nbsp;\u003Cbr \/\u003Ethrough phagocytosis and found that both Fc density and microparticle size\u0026nbsp;\u003Cbr \/\u003Ehad significant impacts on macrophage phagocytosis. These results also\u0026nbsp;\u003Cbr \/\u003Eprovide a particle delivery \u201ctoolbox\u201d for future applications. We then\u0026nbsp;\u003Cbr \/\u003Eanalyzed the downstream effects of Fc particles on macrophage phenotype and\u0026nbsp;\u003Cbr \/\u003Eon phenotype plasticity. This showed that the addition of Fc particles lead\u0026nbsp;\u003Cbr \/\u003Eto increased production of TNF\u03b1 and IL-12 and inverted the response of LPS\u0026nbsp;\u003Cbr \/\u003Etreated macrophages. Finally, we applied our particles to activate the\u0026nbsp;\u003Cbr \/\u003Ecomplement system, an often overlooked cascade of serum protein activation\u0026nbsp;\u003Cbr \/\u003Ethat results in bacterial cell lysis. Cleaved components of the complement\u0026nbsp;\u003Cbr \/\u003Esystem are also powerful chemokines and can act as a vaccine adjuvant. Fc\u0026nbsp;\u003Cbr \/\u003Edensity on particles played a large role in complement system activation,\u0026nbsp;\u003Cbr \/\u003Eboth through the classical and alternative pathway, as it lead to a binary\u0026nbsp;\u003Cbr \/\u003Eresponse for smaller particles and a tunable response for larger particles.\u0026nbsp;\u003Cbr \/\u003EWe then applied these results to create a novel form of antibiotic by using\u0026nbsp;\u003Cbr \/\u003EFc particles to direct complement-mediated bacterial cytotoxicity. The use\u0026nbsp;\u003Cbr \/\u003Eof immune activation by Fc particles was also applied to better understand\u0026nbsp;\u003Cbr \/\u003Eand improve the tuberculosis vaccine. Our findings are significant to the\u0026nbsp;\u003Cbr \/\u003Ebiomaterials and immunology fields as we showed that Fc microparticles can\u0026nbsp;\u003Cbr \/\u003Egenerally be used to alter the immune response in a tunable manner for a\u0026nbsp;\u003Cbr \/\u003Ebroad range of applications, as well answering fundamental immunology\u0026nbsp;\u003Cbr \/\u003Equestions.\u003C\/p\u003E","summary":null,"format":"limited_html"}],"field_subtitle":"","field_summary":"","field_summary_sentence":[{"value":"Fc Coated Micro\/nanoparticles for Humoral Immune System Modulation"}],"uid":"28077","created_gmt":"2014-11-06 17:20:11","changed_gmt":"2016-10-08 02:10:09","author":"Danielle Ramirez","boilerplate_text":"","field_publication":"","field_article_url":"","field_event_time":{"event_time_start":"2014-11-10T08:00:00-05:00","event_time_end":"2014-11-10T10:00:00-05:00","event_time_end_last":"2014-11-10T10:00:00-05:00","gmt_time_start":"2014-11-10 13:00:00","gmt_time_end":"2014-11-10 15:00:00","gmt_time_end_last":"2014-11-10 15:00:00","rrule":null,"timezone":"America\/New_York"},"extras":[],"groups":[{"id":"221981","name":"Graduate Studies"}],"categories":[],"keywords":[{"id":"1808","name":"graduate students"},{"id":"913","name":"PhD"}],"core_research_areas":[],"news_room_topics":[],"event_categories":[{"id":"1788","name":"Other\/Miscellaneous"}],"invited_audience":[{"id":"78761","name":"Faculty\/Staff"}],"affiliations":[],"classification":[],"areas_of_expertise":[],"news_and_recent_appearances":[],"phone":[],"contact":[],"email":[],"slides":[],"orientation":[],"userdata":""}}}