Molecular basis of bioelectronic medicine

生物电子医学的分子基础

• 批准号: 10614430
• 负责人: Kevin J Tracey
• 金额: $ 75.38万
• 依托单位: FEINSTEIN INSTITUTE FOR MEDICAL RESEARCH
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-05-01 至 2026-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10614430
• 关键词: Affect; Alzheimer' s Disease; Anatomy; Arthritis; Asthma; Award; Basic Science; Brain; Clinical Trials; Crohn' s disease; Diabetes Mellitus; Disease model; Electronics; Electrophysiology (science); Environment; Funding; Heart Diseases; Imaging technology; Immune System Diseases; Immune system; Immunity; Immunobiology; Immunology; Inflammation; Inflammatory; Inflammatory Bowel Diseases; Knockout Mice; Lead; Medicine; Methods; Mission; Molecular; National Institute of General Medical Sciences; Natural Immunity; Nervous System; Nervous System control; Neurobiology; Patients; Pharmaceutical Preparations; Publications; Reflex action; Reporting; Research; Rheumatoid Arthritis; Science; Series; Stroke; Transgenic Organisms; Translating; Vagus nerve structure; Work; bioelectronics; clinical investigation; clinical practice; design; experience; innovation; mind control; neural; neurophysiology; neurotransmission; optogenetics; programs; public health relevance

Abstract Research during the last funding period of this NIGMS-funded MIRA award has significantly advanced understanding of the molecular immunobiology mechanisms at the interface between the nervous system and the immune system. As reported in a series of high impact publications, our lab's discoveries of vagus nerve control of inflammation, termed “the inflammatory reflex,” the elucidation of the specific neural and molecular mechanisms, culminated in successful clinical trials in rheumatoid arthritis and Crohn's disease. This NIGMS MIRA-supported work of basic immunobiology programs focuses on the anatomy, electrophysiology, and molecular mechanisms of the vagus nerve circuits controlling innate immunity. It is credited with establishing and leading the field of bioelectronic medicine. The present competing renewal proposes a logical, significant, innovative, and impactful continuation of this work delineating how the brain controls immunity. There remain many major unanswered questions. For example, what is the origin, anatomy, and function in the brain of neural signals that control inflammation? How does the brain sense and record the presence of inflammation in the body? And, what are the brain and nervous system mechanisms that stimulate inflammation? Some of these questions will be answered directly, and other new questions will likely arise during the course of work to guide additional exploration. The PI and his lab have assembled and lead teams to accomplish this work. They have the necessary experience and a track record in using optogenetics, transgenic, and knock-out mice, immunological disease models, imaging technologies, electro- and neuro-physiology methods, and basic immunology and neurobiology. They are in an ideal environment to successfully complete the proposed studies, both to advance the MIRA mission of NIGMS, and to continue their journey translating basic science into clinical investigation and practice.

摘要 在这个NIGMS资助的MIRA奖的最后一个资助期内， 在分子免疫生物学机制的显著进步的理解， 神经系统和免疫系统之间的接口。正如一系列报告所述， 高影响力的出版物，我们实验室的发现迷走神经控制炎症， 被称为“炎症反射”，阐明了特定的神经和分子， 机制，最终在类风湿性关节炎和克罗恩病的成功临床试验 疾病这项由NIGMS MIRA支持的基础免疫生物学项目的工作重点是 迷走神经回路的解剖学、电生理学和分子机制 控制先天免疫它被认为是建立和领导该领域的 生物电子医学目前的竞争性更新提出了一个合乎逻辑的、重要的、 创新的，有影响力的继续这项工作描绘了大脑如何控制 免疫力仍有许多重大问题没有得到解答。例如， 控制炎症的神经信号在大脑中的起源、解剖和功能？如何 大脑是否感知并记录体内炎症的存在？那么， 刺激炎症的大脑和神经系统机制其中一些 问题将得到直接回答，其他新的问题可能会在会议期间出现。 指导进一步的探索。私家侦探和他的实验室已经集合了 带领团队完成这项工作。他们有必要的经验和轨道 在使用光遗传学、转基因和基因敲除小鼠、免疫性疾病 模型、成像技术、电生理学和神经生理学方法， 免疫学和神经生物学。他们在一个理想的环境中成功地完成 拟议的研究，既要推进NIGMS的MIRA使命，又要继续其 将基础科学转化为临床研究和实践的旅程。

项目成果

Organ- and function-specific anatomical organization of vagal fibers supports fascicular vagus nerve stimulation.

• DOI: 10.1016/j.brs.2023.02.003
• 发表时间: 2023-03
• 期刊: BRAIN STIMULATION
• 影响因子: 7.7
• 作者: Jayaprakash, Naveen;Song, Weiguo;Toth, Viktor;Vardhan, Avantika;Levy, Todd;Tomaio, Jacquelyn;Qanud, Khaled;Mughrabi, Ibrahim;Chang, Yao-Chuan;Rob, Moontahinaz;Daytz, Anna;Abbas, Adam;Nassrallah, Zeinab;Volpe, Bruce T.;Tracey, Kevin J.;Al -Abed, Yousef;Datta-Chaudhuri, Timir;Miller, Larry;Barbe, Mary F.;Lee, Sunhee C.;Zanos, Theodoros P.;Zanos, Stavros
• 通讯作者: Zanos, Stavros

Manipulation of the inflammatory reflex as a therapeutic strategy.

• DOI: 10.1016/j.xcrm.2022.100696
• 发表时间: 2022-07-19
• 期刊: CELL REPORTS MEDICINE
• 影响因子: 14.3
• 作者: Kelly, Mark J.;Breathnach, Caitriona;Tracey, Kevin J.;Donnelly, Seamas C.
• 通讯作者: Donnelly, Seamas C.

In-vivo evidence that high mobility group box 1 exerts deleterious effects in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine model and Parkinson's disease which can be attenuated by glycyrrhizin.

• DOI: 10.1016/j.nbd.2016.02.018
• 发表时间: 2016-07
• 期刊: Neurobiology of disease
• 影响因子: 6.1
• 作者: Santoro M;Maetzler W;Stathakos P;Martin HL;Hobert MA;Rattay TW;Gasser T;Forrester JV;Berg D;Tracey KJ;Riedel G;Teismann P
• 通讯作者: Teismann P

Exploring the biological functional mechanism of the HMGB1/TLR4/MD-2 complex by surface plasmon resonance.

• DOI: 10.1186/s10020-018-0023-8
• 发表时间: 2018-05-10
• 期刊: Molecular medicine (Cambridge, Mass.)
• 作者: He M;Bianchi ME;Coleman TR;Tracey KJ;Al-Abed Y
• 通讯作者: Al-Abed Y

Immunization Elicits Antigen-Specific Antibody Sequestration in Dorsal Root Ganglia Sensory Neurons.

• DOI: 10.3389/fimmu.2018.00638
• 发表时间: 2018
• 期刊: Frontiers in immunology
• 影响因子: 7.3
• 作者: Gunasekaran M;Chatterjee PK;Shih A;Imperato GH;Addorisio M;Kumar G;Lee A;Graf JF;Meyer D;Marino M;Puleo C;Ashe J;Cox MA;Mak TW;Bouton C;Sherry B;Diamond B;Andersson U;Coleman TR;Metz CN;Tracey KJ;Chavan SS
• 通讯作者: Chavan SS