{"636804":{"#nid":"636804","#data":{"type":"event","title":"PhD Defense by Jiexi Liao","body":[{"value":"\u003Cp\u003E\u003Cstrong\u003EJiexi Liao\u003C\/strong\u003E\u003C\/p\u003E\r\n\r\n\u003Cp\u003E\u003Cstrong\u003EBME Ph.D. Thesis\u0026nbsp;Defense\u003C\/strong\u003E\u003C\/p\u003E\r\n\r\n\u003Cp\u003E\u0026nbsp;\u003C\/p\u003E\r\n\r\n\u003Cp\u003E\u003Cstrong\u003EDate:\u003C\/strong\u003E\u0026nbsp;07\/16\/2020\u003C\/p\u003E\r\n\r\n\u003Cp\u003E\u003Cstrong\u003ETime:\u0026nbsp;\u003C\/strong\u003E11:00 AM ET\u003C\/p\u003E\r\n\r\n\u003Cp\u003E\u003Cstrong\u003EBlueJeans link:\u003C\/strong\u003E\u0026nbsp;\u003Ca href=\u0022https:\/\/gatech.bluejeans.com\/232841791\u0022\u003Ehttps:\/\/gatech.bluejeans.com\/232841791\u003C\/a\u003E\u003C\/p\u003E\r\n\r\n\u003Cp\u003E\u003Cstrong\u003EMeeting ID:\u003C\/strong\u003E\u0026nbsp;232 841 791\u003C\/p\u003E\r\n\r\n\u003Cp\u003E\u0026nbsp;\u003C\/p\u003E\r\n\r\n\u003Cp\u003E\u003Cstrong\u003EThesis committee:\u003C\/strong\u003E\u003C\/p\u003E\r\n\r\n\u003Cp\u003ECheng Zhu, PhD (Advisor)\u003C\/p\u003E\r\n\r\n\u003Cp\u003EBrian Petrich, PhD (Emory University)\u003C\/p\u003E\r\n\r\n\u003Cp\u003EShaun Jackson, PhD (University of Sydney)\u003C\/p\u003E\r\n\r\n\u003Cp\u003EShuichi Takayama, PhD\u003C\/p\u003E\r\n\r\n\u003Cp\u003EManu Platt, PhD\u0026nbsp;\u003C\/p\u003E\r\n\r\n\u003Cp\u003E\u0026nbsp;\u003C\/p\u003E\r\n\r\n\u003Cp\u003E\u003Cstrong\u003ETitle:\u003C\/strong\u003E\u0026nbsp;Regulation of platelet integrin mechanobiology by talin\u0026nbsp;\u003C\/p\u003E\r\n\r\n\u003Cp\u003E\u0026nbsp;\u003C\/p\u003E\r\n\r\n\u003Cp\u003E\u003Cstrong\u003EAbstract:\u0026nbsp;\u003C\/strong\u003EPlatelets are reactive to mechanical forces in disturbed blood flow caused by vessel branching, stenosis, and interventional medical devices, leading to life-threatening clots composed of platelet aggregates. How forces drive platelet aggregation on the molecular level is incompletely understood. Integrins, particularly the platelet-specific \u0026alpha;IIb\u0026beta;3 (GPIIbIIIa), mediate the gradient shear-induced platelet aggregation not in their fully activated but intermediate state. Since integrins need the cytoplasmic adaptor molecule, talin, for activation and cytoskeletal linkage, elucidating talin\u0026rsquo;s role is critical to understand this process.\u0026nbsp;\u003C\/p\u003E\r\n\r\n\u003Cp\u003E\u0026nbsp;\u003C\/p\u003E\r\n\r\n\u003Cp\u003EUsing stenosis-modeling microfluidics and mouse models that perturb specific interactions in the Rap-1-talin-integrin axis, we first demonstrated that talin indeed regulates platelet aggregation in disturbed flow and proposed the mechanism that aggregate buildup is achieved by membrane-recruited talin providing cytoskeletal linkage to the integrins. To gain mechanistic insights on the molecular level, we used single-cell force spectroscopy to characterize the two-dimensional kinetics of integrin-ligand binding with talin perturbations. We found that talin, a mechanosensor itself, is particularly important for force-mediated integrin binding without prior inside-out activation. The formation of catch bond (force prolonged bond lifetime) between the fibrinogen ligand and \u0026beta;3 integrin may be crucial for platelet aggregation in disturbed flow. Lastly, we extended the platelet mechanobiology study to investigate a disease that bears a pathology independent of cardiovascular aberration but is known to dysregulate platelets: diabetes. Using the stenosis microfluidics to screen patients\u0026rsquo; blood, we preliminarily concluded that type I diabetes could amplify platelet aggregation by promoting more integrins to the intermediate state, but many other factors including racial heritage could cause large variance in patient samples\u0026rsquo; responses.\u003C\/p\u003E\r\n\r\n\u003Cp\u003E\u0026nbsp;\u003C\/p\u003E\r\n\r\n\u003Cp\u003EOverall, we identified talin\u0026rsquo;s critical role in gradient shear-induced platelet aggregation. The biophysics studies offered a clearer understanding of how integrins finely tune their kinetics in response to mechanical cues. Our results showed anti-thrombotic potential of specific talin and Rap1 blockade and could inform design of novel therapeutics that address the mechanosensitivity of integrins.\u0026nbsp;\u0026nbsp;\u0026nbsp;\u003C\/p\u003E\r\n","summary":null,"format":"limited_html"}],"field_subtitle":"","field_summary":"","field_summary_sentence":[{"value":"Regulation of platelet integrin mechanobiology by talin "}],"uid":"27707","created_gmt":"2020-07-08 12:28:29","changed_gmt":"2020-07-08 12:28:29","author":"Tatianna Richardson","boilerplate_text":"","field_publication":"","field_article_url":"","field_event_time":{"event_time_start":"2020-07-16T12:00:00-04:00","event_time_end":"2020-07-16T14:00:00-04:00","event_time_end_last":"2020-07-16T14:00:00-04:00","gmt_time_start":"2020-07-16 16:00:00","gmt_time_end":"2020-07-16 18:00:00","gmt_time_end_last":"2020-07-16 18:00:00","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":""}}}