BLRD Research Career Scientist Award Application

这项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 这是专注于研究细胞外囊泡（EV）和它们的细胞外RNA（exRNA）货物， 包括退伍军人在内的人类健康和疾病的生物标志物和效应物。通过参加 国家NIH资助的财团研究计划，被提名人正在努力开发新的方法来研究 EV和其他exRNA载体用于生物标志物开发项目。被提名人最近还报告说， 第一个证据表明巨噬细胞EV和造血祖细胞之间的细胞间信号传导，以控制 全身和血管炎症和动脉粥样硬化心血管疾病的过程。 来自VA Merit赠款的持续资金正在支持被提名人探索循环电动汽车作用的目标 分离自接受晚期血管疾病治疗的退伍军人，作为疾病的生物标志物和贡献者 包括通过microRNA货物的进展。实验室中的实验还将测试电动汽车是否由抗- 炎性巨噬细胞可用于控制糖尿病啮齿动物模型中的炎症和动脉粥样硬化。 此外，VA基于发明的补充奖的资金将支持临床前研究， 抗炎EV作为控制啮齿动物模型系统中心脏炎症和心力衰竭的治疗剂 由被提名人为退伍军人管理局开发并申请专利。这些研究的结果可以提供急需的 以EV生物制剂形式治疗炎性疾病（包括心血管疾病）的新疗法 这是退伍军人患者群体的主要医疗保健需求。 被提名者的EV生物学国际公认的计划导致了新的合作研究项目 与当地和异地工作站的退伍军人管理局临床研究人员一起。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介质。这类研究 在VA Merit Grant提案中提出，被提名人担任共同研究者，该提案正在修订中 重新提交被提名者还与VA临床研究人员进行合作研究， 开发用于治疗晚期血管疾病的外科手术不良结局的生物标志物， 老兵最后，被提名人通过退伍军人事务部和 NIH利用被提名人开发的EV技术和专业知识来解决COVID 19疾病 危机这包括通过利用生物流体中EV检测的新方法来开发用于临床的生物标志物， COVID 19疾病的结果。它还包括开发新形式的工程电动汽车， 提高宿主对SARS-CoV-2病毒感染的免疫应答以及控制肺部炎症。 总之，该奖项将有助于维持被提名人的势头，以发展一流的研究 该项目以EV作为生物标志物和生物制剂的研究为中心，以控制组织炎症和重塑 包括心血管系统。它还将允许扩大合作者的提名网络， 临床医生和基础科学家在VA内部研究计划，以及在地方，国家和 国际网站，广泛传播和实施电动汽车作为生物制品研究的专业知识，以提高 诊断和治疗VA优先领域的疾病。此外，它将允许被提名人增加 为地方和国家委员会提供专业服务，包括在VA内，并保持教学和 指导VA研究计划中的下一代研究人员和临床科学家。

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.