{"625657":{"#nid":"625657","#data":{"type":"event","title":"Phd Proposal by Michael Sayegh","body":[{"value":"\u003Cp\u003E\u003Cstrong\u003EMichael Sayegh\u003C\/strong\u003E\u003C\/p\u003E\r\n\r\n\u003Cp\u003E\u003Cstrong\u003EBME PhD 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;September 18, 2019\u003C\/strong\u003E\u003C\/p\u003E\r\n\r\n\u003Cp\u003E\u003Cstrong\u003ETime:\u0026nbsp;9:00-10:00 AM\u003C\/strong\u003E\u003C\/p\u003E\r\n\r\n\u003Cp\u003E\u003Cstrong\u003ELocation:\u0026nbsp;\u003C\/strong\u003EEUH Hurst Conference Room (E450)\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\u003ERebecca D. Levit, MD (Advisor)\u003C\/p\u003E\r\n\r\n\u003Cp\u003EW. Robert Taylor, MD PhD\u003C\/p\u003E\r\n\r\n\u003Cp\u003EAndr\u0026eacute;s J. Garc\u0026iacute;a, PhD\u0026nbsp;\u003C\/p\u003E\r\n\r\n\u003Cp\u003ERabindra Tirouvanziam, PhD\u003C\/p\u003E\r\n\r\n\u003Cp\u003ENick Willett, PhD\u003C\/p\u003E\r\n\r\n\u003Cp\u003E\u0026nbsp;\u003C\/p\u003E\r\n\r\n\u003Cp\u003E\u003Cstrong\u003ETitle: A biomaterials approach to inhibit neutrophils extracellular traps in cardiac ischemia and reperfusion injury\u003C\/strong\u003E\u003C\/p\u003E\r\n\r\n\u003Cp\u003E\u0026nbsp;\u003C\/p\u003E\r\n\r\n\u003Cp\u003E\u003Cstrong\u003EThesis proposal abstract:\u003C\/strong\u003E\u003C\/p\u003E\r\n\r\n\u003Cp\u003EDespite great advances, ischemic heart disease is still the leading cause of death worldwide, and novel interventions are needed to improve outcomes.\u0026nbsp;This proposal takes\u0026nbsp;a dual\u0026nbsp;investigative and therapeutic approach to neutrophil extracellular trap\u0026nbsp;(NET)\u0026nbsp;involvement in myocardial\u0026nbsp;ischemia\u0026nbsp;and reperfusion injury (MI\/R). In\u0026nbsp;Aim 1, we\u0026nbsp;will\u0026nbsp;parse the specific cell types among the main cardiac cell populations that are susceptible to NET-induced damage. We then study the effect of introducing NETs into a healthy heart on contraction,\u0026nbsp;immune infiltration, and subsequent fibrosis. Finally, we seek a mechanism of NET damage by screening for cytokine responses and Toll-like receptor (TLR) mediators.\u0026nbsp;In\u0026nbsp;Aim 2, we engineer an adenosine delivery vehicle to inhibit NETosis a priori.\u0026nbsp;Considering its\u0026nbsp;dose-limiting side-effects\u0026nbsp;and short\u0026nbsp;half-life\u0026nbsp;in circulation,\u0026nbsp;adenosine is impractical to\u0026nbsp;deliver\u0026nbsp;directly. Instead,\u0026nbsp;we\u0026nbsp;embed\u0026nbsp;an enzyme, CD73, that catalyzes the rate-limiting step in endogenous adenosine formation, in a\u0026nbsp;polyethylene glycol 4-maleimide (PEG-4MAL) hydrogel, and test\u0026nbsp;parameters\u0026nbsp;of the gel\u0026nbsp;and variations\u0026nbsp;on the cargo,\u0026nbsp;to\u0026nbsp;evaluate their function in producing adenosine. Then we use our adenosine delivery tool, the CD73 functionalized hydrogel, to inhibit reactive oxygen species (ROS) production and NETosis in vitro.\u0026nbsp;In\u0026nbsp;Aim 3, we\u0026nbsp;propose to\u0026nbsp;deliver the best performing gels in vivo and test their ability to augment cardiac adenosine. We\u0026nbsp;will\u0026nbsp;apply the gel onto a rat model of MI\/R and measure its ability to reduce scar size and preserve cardiac function, in correlation with decreased immune infiltration and MI\/R-induced NETosis, and improved vascular perfusion.\u0026nbsp;\u003C\/p\u003E\r\n\r\n\u003Cp\u003ETherefore, by increasing the availability of a\u0026nbsp;NET inhibitor and\u0026nbsp;anti-inflammatory drug, adenosine, from substrate released in myocardial ischemic damage,\u0026nbsp;we aim to reduce the negative sequelae of MI\/R, and establish\u0026nbsp;proof of concept for a clinically\u0026nbsp;translatable\u0026nbsp;biomaterial.\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":"A biomaterials approach to inhibit neutrophils extracellular traps in cardiac ischemia and reperfusion injury"}],"uid":"27707","created_gmt":"2019-09-05 13:56:08","changed_gmt":"2019-09-05 13:56:08","author":"Tatianna Richardson","boilerplate_text":"","field_publication":"","field_article_url":"","field_event_time":{"event_time_start":"2019-09-18T10:00:00-04:00","event_time_end":"2019-09-18T11:00:00-04:00","event_time_end_last":"2019-09-18T11:00:00-04:00","gmt_time_start":"2019-09-18 14:00:00","gmt_time_end":"2019-09-18 15:00:00","gmt_time_end_last":"2019-09-18 15:00:00","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":""}}}