{"647284":{"#nid":"647284","#data":{"type":"event","title":"PhD Defense 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 Defense 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\u003EMay 19, 2021\u003C\/p\u003E\r\n\r\n\u003Cp\u003E\u003Cstrong\u003ETime:\u0026nbsp;\u003C\/strong\u003E3:00 PM\u003C\/p\u003E\r\n\r\n\u003Cp\u003E\u003Cstrong\u003EZoom Link:\u0026nbsp;\u003C\/strong\u003E\u003Ca href=\u0022https:\/\/zoom.us\/j\/98388084429\u0022\u003Ehttps:\/\/zoom.us\/j\/98388084429\u003C\/a\u003E \u0026nbsp;\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: \u003C\/strong\u003EPurinergic hydrogels for cardiovascular applications\u003C\/p\u003E\r\n\r\n\u003Cp\u003E\u0026nbsp;\u003C\/p\u003E\r\n\r\n\u003Cp\u003E\u003Cstrong\u003EThesis abstract:\u003C\/strong\u003E\u003C\/p\u003E\r\n\r\n\u003Cp\u003EDespite great advances, ischemic cardiovascular disease is still the leading cause of morbidity and mortality, and novel interventions are needed to improve outcomes. The best current treatment for ischemia, rapid reperfusion via percutaneous coronary intervention, causes subsequent injury due to return of bloodborne oxygen and inflammatory agents.\u003C\/p\u003E\r\n\r\n\u003Cp\u003E\u0026nbsp;\u003C\/p\u003E\r\n\r\n\u003Cp\u003EThe innate immune system orchestrates a complex, multi-phasic response to ischemia\/reperfusion injury. Neutrophils are the earliest cells to infiltrate, and neutrophil extracellular traps (NETs) are spuriously generated, worsening inflammation. Adenosine is a known anti-inflammatory and vasodilatory agent, and a potent inhibitor of NETs in vitro. However,\u0026nbsp; the short lifespan of adenosine in circulation and its dose-limiting side effects complicate systemic administration.\u0026nbsp; Endogenous sources of adenosine include the ecto-nucleotidases CD39 and CD73, which catalyze its production from the phosphorylated adenine nucleotides.\u003C\/p\u003E\r\n\r\n\u003Cp\u003E\u0026nbsp;\u003C\/p\u003E\r\n\r\n\u003Cp\u003EIn this work, we first tested the role of NETs in myocardial injury in vitro using cardiomyocyte cultures, and in vivo by NET introduction into health hearts. We investigated the mechanism of NET induced cardiac dysfunction by increased leukocyte infiltration and fibrosis. We tested a CD73-functionalized PEG hydrogel for neutrophil inhibition in vitro and adenosine augmentation in the ischemic mouse hindlimb. We saw an increase in hindlimb perfusion in response to the CD73-functionalized hydrogel. Combined CD39 and CD73 functionalization of a higher density hydrogel extended the release time and widened the pool of substrate for the enzyme cargo. Delivery of CD39 and CD73 functionalized hydrogels to the heart preserved cardiac function post-ischemia\/reperfusion and decreased markers of immune activation and NETosis.\u003C\/p\u003E\r\n\r\n\u003Cp\u003E\u0026nbsp;\u003C\/p\u003E\r\n\r\n\u003Cp\u003EOur approach for local, sustained and on-demand adenosine augmentation via biomaterial-supported enzymes allows the examination of the role of adenosine in counteracting novel disease processes such as NETosis, unlocks the anti-inflammatory and perfusion benefits of adenosine and widens its application as a therapeutic in ischemic cardiovascular disease.\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":"Purinergic hydrogels for cardiovascular applications"}],"uid":"27707","created_gmt":"2021-05-10 14:22:56","changed_gmt":"2021-05-10 14:22:56","author":"Tatianna Richardson","boilerplate_text":"","field_publication":"","field_article_url":"","field_event_time":{"event_time_start":"2021-05-19T16:00:00-04:00","event_time_end":"2021-05-19T18:00:00-04:00","event_time_end_last":"2021-05-19T18:00:00-04:00","gmt_time_start":"2021-05-19 20:00:00","gmt_time_end":"2021-05-19 22:00:00","gmt_time_end_last":"2021-05-19 22:00:00","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":""}}}