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.

抽象的 在 NIGMS 资助的 MIRA 奖的最后一个资助期内的研究 对显着分子免疫生物学机制的深入了解 正如一系列报道所报道的，神经系统和免疫系统之间的界面。 高影响力的出版物，我们实验室的迷走神经控制炎症的发现， 称为“炎症反射”，阐明特定的神经和分子 机制，最终在类风湿性关节炎和克罗恩病的临床试验中取得成功 NIGMS MIRA 支持的基础免疫生物学项目的工作重点是疾病。 迷走神经回路的解剖学、电生理学和分子机制 它被认为建立并引领了先天免疫领域。 目前的竞争性更新提议是一个合乎逻辑的、重要的、 这项工作的创新且有影响力的延续，描述了大脑如何控制 还有许多重大问题没有得到解答，例如，什么是免疫力。 控制炎症的神经信号的起源、解剖结构和功能？ 大脑是否感知并记录体内炎症的存在？ 刺激炎症的大脑和神经系统机制？ 问题将得到直接回答，期间可能会出现其他新问题 PI 和他的实验室已经收集并编写了额外的探索指南。 他们拥有领导团队完成这项工作所需的经验和轨迹。 使用光遗传学、转基因和基因敲除小鼠、免疫疾病的记录 模型、成像技术、电生理学和神经生理学方法以及基础 他们处于成功完成免疫学和神经生物学的理想环境中。 拟议的研究，既是为了推进 NIGMS 的 MIRA 任务，也是为了继续他们的研究 将基础科学转化为临床研究和实践的旅程。

项目成果

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

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.

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

Focused ultrasound neuromodulation of the spleen activates an anti-inflammatory response in humans.

• DOI: 10.1016/j.brs.2023.04.003
• 发表时间: 2023-05
• 期刊: Brain stimulation
• 影响因子: 7.7
• 作者: Zanos S;Ntiloudi D;Pellerito J;Ramdeo R;Graf J;Wallace K;Cotero V;Ashe J;Moon J;Addorisio M;Shoudy D;Coleman TR;Brines M;Puleo C;Tracey KJ;Chavan SS
• 通讯作者: Chavan SS