{"654628":{"#nid":"654628","#data":{"type":"event","title":"PhD Proposal by Anirudh Sivakumar","body":[{"value":"\u003Cp\u003EAnirudh Sivakumar\u003Cbr \/\u003E\r\nBME PhD Proposal Presentation\u003Cbr \/\u003E\r\n\u003Cbr \/\u003E\r\n\u003Cstrong\u003EDate\u003C\/strong\u003E:2022-02-07\u003Cbr \/\u003E\r\n\u003Cstrong\u003ETime\u003C\/strong\u003E: 2:00 PM\u003Cbr \/\u003E\r\n\u003Cstrong\u003ELocation \/ Meeting Link\u003C\/strong\u003E: IBB Suddath Seminar Room 1128 \/ Virtual Link: \u003Ca href=\u0022https:\/\/bluejeans.com\/518957531\/4900\u0022\u003Ehttps:\/\/bluejeans.com\/518957531\/4900\u003C\/a\u003E\u003Cbr \/\u003E\r\n\u003Cbr \/\u003E\r\n\u003Cstrong\u003ECommittee Members:\u003C\/strong\u003E\u003Cbr \/\u003E\r\nGabe Kwong, PhD (Advisor), M.G. Finn, PhD, Peng Qiu, PhD, Erik Dreaden, PhD, John Blazeck, PhD\u003Cbr \/\u003E\r\n\u003Cbr \/\u003E\r\n\u003Cbr \/\u003E\r\n\u003Cstrong\u003ETitle\u003C\/strong\u003E: Logic-gated activity sensors for programmable cancer diagnostics\u003Cbr \/\u003E\r\n\u003Cbr \/\u003E\r\n\u003Cstrong\u003EAbstract\u003C\/strong\u003E: Advances in synthetic biology are playing a fundamental role in shaping the future of cancer diagnostics toward disease detection and treatment monitoring with higher precision. For example, in engineered T cells, sense-and-respond components that employ AND, OR, or NOT gates have been demonstrated for multiplexed and logical control of T cell responses to increase specificity of tumor-antigen recognition. These advances highlight the promise of synthetic biology for cancer applications, yet the vast majority of these strategies rely on genetic circuits and non-endogenous components, which are complex and may raise safety and immunogenicity concerns for regulatory approval. Therefore, there are outstanding opportunities to apply cell- and gene-free sensors that implement concepts from synthetic biology toward cancer applications. The objective of this thesis proposal is to develop AND-gated protease sensors that integrate design principles from synthetic biology for programmable immune sensing. Protease dysregulation underpins the hallmarks of cancer and immunity and has driven the development of activity-based nanosensors, a class of cell- and gene-free sensors that are administered systemically to query sites of disease and release a reporter upon proteolysis that can be detected in urine. Building on this work, this proposal will design and validate AND-gated activity sensors consisting of nanoparticles conjugated with cyclic peptides that release a reporter only in the presence of protease pairs by implementing AND gate logic. This concept will be tested in the context of anti-tumor T cell immunity. Secretion of proteases called granzymes is fundamental to T cell cytotoxicity but not specific to anti-tumor responses. Therefore, AND-gated sensing of granzymes and cancer-associated matrix metalloproteinases (MMPs) \u0026ndash; which are implicated in several fundamental tumor processes \u0026ndash; may increase selectivity for detection of anti-tumor immune activity. This proposal will design cyclic peptides that perform AND-gated sensing of granzymes and MMPs (Aim 1), develop mathematical models to predict design parameters that affect specificity (Aim 2), and evaluate urinary biomarkers produced by AND-gated sensors for noninvasive detection of anti-tumor responses to immune checkpoint blockade therapy (Aim 3). This proposal will lay the groundwork for the future design of cell- and gene-free sensors for logic-based cancer diagnostics.\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":"Logic-gated activity sensors for programmable cancer diagnostics"}],"uid":"27707","created_gmt":"2022-01-20 16:03:37","changed_gmt":"2022-01-20 16:03:37","author":"Tatianna Richardson","boilerplate_text":"","field_publication":"","field_article_url":"","field_event_time":{"event_time_start":"2022-02-07T14:00:00-05:00","event_time_end":"2022-02-07T16:00:00-05:00","event_time_end_last":"2022-02-07T16:00:00-05:00","gmt_time_start":"2022-02-07 19:00:00","gmt_time_end":"2022-02-07 21:00:00","gmt_time_end_last":"2022-02-07 21:00:00","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":"177814","name":"Postdoc"},{"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":""}}}