BLRD Research Career Scientist Award Application

BLRD 研究职业科学家奖申请

• 批准号: 10618158
• 负责人: Robert Raffai
• 金额: --
• 依托单位: VETERANS AFFAIRS MED CTR SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-04-01 至 2026-03-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10618158
• 关键词: 2019-nCoV; Achievement; Address; Alzheimer' s disease model; Anti-Inflammatory Agents; Apolipoprotein E; Applications Grants; Area; Atherosclerosis; Award; Biological Markers; Biological Models; Biological Products; Biology; Blood Vessels; COVID-19; Cardiovascular Diseases; Cardiovascular system; Cells; Circulation; Clinical; Collaborations; Communication; Coronary Arteriosclerosis; Country; Detection; Diagnosis; Diet; Disclosure; Disease; Disease Progression; Educational process of instructing; Engineering; Faculty; Fostering; Foundations; Funding; Goals; Grant; Growth; Health; Healthcare; Healthcare Systems; Heart failure; Hematopoietic stem cells; Host Defense; Human; Immune; Immune response; Immunologic Tests; Inflammation; Inflammatory; Institution; Intellectual Property; International; Intramural Research Program; Journals; Laboratories; Legal patent; Los Angeles; Macrophage; Mediator; Medical Research; Medical Students; Medical center; Mentors; Methods; MicroRNAs; Mission; Molecular; Myocarditis; Operative Surgical Procedures; Outcome; Pathogenesis; Peripheral; Postdoctoral Fellow; Principal Investigator; Process; Professional Organizations; Property Rights; Publications; Publishing; Pulmonary Inflammation; RNA; Reporting; Research; Research Personnel; Research Project Grants; Resources; Rodent Model; Role; Scientist; Services; Signal Transduction; Site; Skeletal Muscle; Technology; Testing; Therapeutic; Tissues; Translations; United States National Institutes of Health; Vascular Diseases; Ventricular Remodeling; Veterans; Virus; Virus Diseases; adverse outcome; biomarker development; career; design; diabetic; experimental study; extracellular; extracellular vesicles; fighting; graduate student; health care delivery; improved; insight; invention; muscle regeneration; neuroinflammation; next generation; novel; novel therapeutics; patient population; preclinical study; programs; recruit; research and development; stem cells; systemic inflammatory response; therapeutic evaluation; therapy development; tissue repair; vascular inflammation

The overall goal of this Research Career Scientist award is to foster the nominee’s ongoing research program that is focused on the study of extracellular vesicles (EVs) and their extracellular RNA (exRNA) cargo as biomarkers and effectors of human health and disease including among Veterans. Through participation in a national NIH-funded consortium research program, the nominee is working to develop novel methods to study EVs and other carriers of exRNA for biomarker development projects. The nominee also recently reported the first evidence of intercellular signaling between macrophage EVs and hematopoietic progenitor cells to control the process of systemic and vascular inflammation and atherosclerosis cardiovascular disease. Ongoing funding from a VA Merit grant is supporting the nominee’s goal of exploring the role of circulating EVs isolated from Veterans treated for advanced vascular disease as biomarkers and contributors to disease progression including via microRNA cargo. Experiments in the lab will also test if EVs produced from anti- inflammatory macrophages can serve to control inflammation and atherosclerosis in diabetic rodent models. Furthermore, funding from a VA Invention-based Supplement Award will support pre-clinical studies testing such anti-inflammatory EVs as therapeutics to control cardiac inflammation and heart failure in a rodent model system developed and patented for the VA by the nominee. Findings from these studies could provide much needed new therapeutics in the form of EV-biologics to treat inflammatory diseases including in the cardiovascular system that is a major healthcare need among the Veteran patient population. The nominee’s internationally recognized program on EV biology has led to new collaborative research projects with VA clinician investigators at the local and offsite stations. This includes a collaborative project to test EVs produced by cultured stem cells as therapeutic mediators of skeletal muscle regeneration. Such studies have been proposed in a VA Merit grant proposal with the nominee serving as co-Investigator, which is being revised for a resubmission. The nominee is also engaged in collaborative studies with VA clinician investigators to develop biomarkers of adverse outcomes of surgical procedures used to treat advanced vascular disease among Veterans. Finally, projects proposed by the nominee through grants pending at the Department of VA and the NIH make use of EV technology and expertise developed by the nominee to address the COVID19 disease crisis. This includes by making use of new methods of EV detection in biofluids to develop biomarkers for clinical outcomes of COVID19 disease. It also includes developing new forms of engineered EVs designed to serve in improving host immune response against SARS-CoV-2 viral infection as well as to control lung inflammation. Together, the award will serve to sustain the nominee’s momentum to developing a first-in-class research program centered on the study of EVs as biomarkers and biologics to control tissue inflammation and remodeling including in the cardiovascular system. It will also allow to expand the nominees network of collaborators with clinician and basic scientists within the VA intramural research program, as well as at local, national and international sites to widely disseminate and implement expertise in the study of EVs as biologics to improve the diagnosis and treatment of diseases in priority areas to the VA. Furthermore, it will allow the nominee to increase professional service to local and national committees including within the VA and maintain teaching and mentoring to next generation research investigators and clinician scientists within the VA research program.

这个研究职业科学家奖的总体目标是促进被提名者正在进行的研究计划 主要研究胞外小泡(EV)及其胞外RNA(ExRNA)。 包括退伍军人在内的人类健康和疾病的生物标记物和效应物。通过参与 国家国立卫生研究院资助的联合研究计划，被提名者正在努力开发新的方法来研究 电动汽车和其他外源RNA载体，用于生物标记物开发项目。这位被提名人最近还报道了 巨噬细胞EV和造血祖细胞之间细胞间信号转导的首个证据 全身和血管炎症和动脉粥样硬化心血管疾病的过程。 来自退伍军人事务部奖励金的持续资金支持了被提名者探索流通电动汽车作用的目标 从接受晚期血管疾病治疗的退伍军人中分离出来作为生物标记物和疾病贡献者 进展，包括通过microRNA货物。实验室中的实验还将测试由反电动汽车生产的电动汽车是否 炎性巨噬细胞可用于控制糖尿病啮齿动物模型的炎症和动脉粥样硬化。 此外，退伍军人管理局基于发明的补充奖的资金将支持临床前研究 作为治疗药物的抗炎EVS在啮齿动物模型系统中控制心脏炎症和心力衰竭 由被提名者为退伍军人管理局开发并申请专利。这些研究的结果可能会提供急需的 以肠道生物制剂的形式治疗包括心血管在内的炎症性疾病的新疗法 这一系统是退伍军人患者群体中的主要医疗需求。 被提名者在电动汽车生物学方面的国际认可项目导致了新的合作研究项目 与退伍军人管理局临床医生在当地和异地站的调查人员一起。这包括一个测试电动汽车的合作项目 由培养的干细胞产生，作为骨骼肌再生的治疗媒介。这类研究已经 在退伍军人事务部奖励金提案中提出，被提名人担任联合调查员，该提案正在修订中 重新提交申请。被提名人还参与了与退伍军人管理局临床医生研究人员的合作研究，以 开发用于治疗晚期血管疾病的外科手术的不良结果的生物标记物 退伍军人。最后，被提名人通过退伍军人事务部和 NIH利用EV技术和被提名者开发的专业知识来应对COVID19疾病 危机。这包括利用新的体液中肠病毒检测方法来开发用于临床的生物标记物。 COVID19疾病的转归。它还包括开发新形式的工程化电动汽车，旨在为 改善宿主对SARS-CoV-2病毒感染的免疫反应，控制肺部炎症。 总而言之，该奖项将有助于保持被提名者发展一流研究的势头 以EVS作为生物标记物和生物制品来控制组织炎症和重塑的研究计划 包括心血管系统。它还将允许通过以下方式扩大被提名的合作者网络 退伍军人事务部内部研究方案内的临床医生和基础科学家以及地方、国家和 国际网站广泛传播和实施电动汽车作为生物制品的研究专业知识，以改善 退伍军人事务部优先领域疾病的诊断和治疗。此外，它还将允许提名者增加 为地方和国家委员会提供专业服务，包括在退伍军人事务部内，并维持教学和 在退伍军人管理局研究计划内指导下一代研究人员和临床科学家。

项目成果

ApoE expression in macrophages communicates immunometabolic signaling that controls hyperlipidemia-driven hematopoiesis & inflammation via extracellular vesicles.

• DOI: 10.1002/jev2.12345
• 发表时间: 2023-08
• 期刊: Journal of extracellular vesicles
• 影响因子: 16

High glucose macrophage exosomes enhance atherosclerosis by driving cellular proliferation & hematopoiesis.

• DOI: 10.1016/j.isci.2021.102847
• 发表时间: 2021-08-20
• 期刊: iScience
• 影响因子: 5.8
• 作者: Bouchareychas L;Duong P;Phu TA;Alsop E;Meechoovet B;Reiman R;Ng M;Yamamoto R;Nakauchi H;Gasper WJ;Van Keuren-Jensen K;Raffai RL
• 通讯作者: Raffai RL

Visualizing transfer of microbial biomolecules by outer membrane vesicles in microbe-host-communication in vivo.

• DOI: 10.1002/jev2.12159
• 发表时间: 2021-10
• 期刊: Journal of extracellular vesicles
• 影响因子: 16
• 作者: Bittel M;Reichert P;Sarfati I;Dressel A;Leikam S;Uderhardt S;Stolzer I;Phu TA;Ng M;Vu NK;Tenzer S;Distler U;Wirtz S;Rothhammer V;Neurath MF;Raffai RL;Günther C;Momma S
• 通讯作者: Momma S