Laboratory for Combinatorial Drug Regimen Design for Resistant and Emerging Pathogens

耐药和新发病原体组合药物方案设计实验室

• 批准号: 10596722
• 负责人: Linden T Hu
• 金额: $ 514.71万
• 依托单位: TUFTS UNIVERSITY BOSTON
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-09-16 至 2024-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10596722
• 关键词: Academia; Address; Affect; Animals; Antimicrobial Resistance; Back; Bacteria; Bacterial Infections; Biomedical Research; Boston; COVID-19 pandemic; Centers for Disease Control and Prevention (U.S.); Clinical; Clinical Data; Collaborations; Combined Modality Therapy; Communicable Diseases; Country; Development; Drug Combinations; Education; Emergency Situation; Emerging Communicable Diseases; Engineering; Environment; Equipment; Faculty; Feedback; Genetic; Glossary; Goals; HIV/TB; Health; Health Sciences; Hospitals; Human; Incidence; Industrialization; Industry; Infection; Insecta; Institution; Knowledge; Laboratories; Libraries; Link; Measures; Medical center; Medicine; Modernization; Multi-Drug Resistance; Mycoses; National Security; New England; Parasitic infection; Pathogenicity; Patient-Focused Outcomes; Patients; Pharmaceutical Preparations; Pharmacologic Substance; Pharmacotherapy; Policies; Population Heterogeneity; Public Health; Readiness; Regimen; Research; Research Personnel; Resistance; Resources; Schools; Scientist; Security; System; Technology; Therapeutic; Training; Treatment Protocols; Universities; Veterinary Medicine; Veterinary Schools; Viral; Virus Diseases; Visit; Work; antimicrobial; antimicrobial drug; bench to bedside; clinical practice; combat; combinatorial; design; drug efficacy; emerging pathogen; global health; improved; innovation; interest; member; multi-drug resistant pathogen; novel; novel therapeutics; pandemic disease; pathogen; pathogenic bacteria; pathogenic microbe; pathogenic virus; personalized medicine; research facility; response; square foot

(a) Overview The past two years have shown that infectious diseases are global threats, revealing an urgent need to improve preparedness to combat unknown pathogens. Furthermore, the alarming increase in infections caused by antimicrobial resistant (AMR; see glossary, below) pathogens in recent years, exacerbated by the COVID-19 pandemic, illustrates that we are also on the verge of losing our ability to treat infections caused by known pathogens. Combination drug treatment is the therapeutic mainstay in the treatment of infections caused by several microbial pathogens, including HIV and the tuberculosis bacterium. Still, systematic and efficient development of such treatments for AMR or emerging pathogens is lacking. Tufts University (TU) is proposing to construct a new biomedical research facility, the Laboratory for Combinatorial Drug Regimen Design for Resistant and Emerging Pathogens (LCDRD), to design and develop new combinatorial therapeutic approaches for bacterial, viral, fungal, and parasitic infections and to accelerate research on AMR and emerging pandemic pathogens. The LCDRD is designed to facilitate the development of novel treatments for difficult-to-treat infections due to pathogens from both animals and humans. In addition to generating new therapies for AMR or emerging pathogens, this facility will provide diverse, well-characterized human bacterial pathogens with linked clinical data from across ‘Tufts-Medicine’, a state-wide network of hospitals serving diverse populations, for study by academia and industry. The Stuart B. Levy Tufts Center for Integrative Management of Antimicrobial Resistance (CIMAR) unites faculty from TU and Tufts Medical Center (TMC), as well as affiliate members from across the region and nation, with expertise in biomedical research, engineering, human and veterinary medicine, global health, environmental surveillance, policy, and education, to catalyze the development of new combinatorial drug strategies to treat a wide range of pathogens. Working with CIMAR in LCDRD will be the nascent Center for Emerging Infectious Diseases and Response (CEIDAR), which addresses emerging and expanding infectious disease threats such as insect-borne bacterial and viral pathogens. CEIDAR includes the Tufts Lyme Initiative and utilizes the BSL-3 level Tufts New England Regional Biosafety Laboratory (NERBL) at Tufts Cummings School of Veterinary Medicine in Grafton, an important resource for expanding work. Institutions affiliated with CIMAR/CEIDAR span a spectrum of academic and pharmaceutical interests and, although located locally at TU, will enhance transdisciplinary interactions among regional and national investigators and entities. Project Goals: The LCDRD will enable specialized and collaborative work on emerging and resistant microbial pathogens that is required to generate new combinatorial treatments. The facility will: 1) enhance interaction between clinicians and biomedical researchers to generate therapeutic antimicrobial drug regimens, particularly combination therapies, against CDCs urgent and emerging threat pathogens; 2) develop genetic and systems approaches to facilitate ‘personalized medicine’ for patients with difficult-to-treat infection; 3) provide a space where visiting scientists can receive hands-on training, allowing knowledge dissemination intra-institutionally, regionally, nationally, and globally; and 4) increase the national capacity to respond to infectious disease emergencies by providing academic and industrial entities access to libraries of well-characterized isolates for emerging pandemic and AMR pathogens. Affected Space and Requested Equipment: The LCDRD will provide a modern, centralized laboratory and collaboration capacity for a multi-institutional effort to utilize state-of-the-art research technologies to generate and characterize novel drug therapies for pathogens resistant to current therapeutic regimens as well as new pandemic threats. It will provide a specialized and biosecure environment for researchers to work with multi- drug resistant (MDR) and emerging pathogens. It will be built in an existing 2,400 sq. ft. shell space in the Biomedical Research and Public Health Building on the Tufts Health Sciences campus in Boston. The new facility, directly adjacent to Tufts’ existing BSL-3 lab and the laboratories of the PI and a key CIMAR investigator, will be shared by teams of interdisciplinary researchers from four TU schools and TMC, as well as collaborators from other regional and national institutions. Impact on Research and Clinical Practice: The National Health Security Strategy, 2019-2022, states that “the growing incidence of AMR has both public health and national security consequences” and that “expanding the antimicrobial arsenal is a real and immediate requirement to avoid an era of untreatable infectious diseases.” Through centralizing and leveraging our expertise in bacterial, viral, and MDR pathogens, innovative measures of combinatorial drug efficacy, and deep clinical expertise in treatment-resistant infections, the LCDRD will support the nation’s AMR crisis response by generating novel therapies, both at Tufts and in collaboration with other academic and pharmaceutical entities across the country (Fig. 1). LCDRD will be a national center of excellence that makes broadly available well-characterized pathogens with clinical data, allowing for linkage of patient outcomes to strain-level pathogenicity and combination therapy. This will enable a true link from bedside to bench and back—a feedback loop that will maintain a tight translational focus, inform treatment regimens for current and emerging threats, and promote personalized medicine.

(a)概述 过去两年的情况表明，传染病是全球性的威胁，这表明迫切需要改进 做好应对未知病原体的准备。此外，由于艾滋病毒/艾滋病引起的感染令人震惊地增加， 近年来，新型冠状病毒肺炎（COVID-19）加剧了抗生素耐药（AMR;见下文术语表）病原体 大流行病，表明我们也即将失去治疗由已知疾病引起的感染的能力。 病原体联合药物治疗是治疗由感染引起的感染的主要治疗方法。 几种微生物病原体，包括艾滋病毒和结核菌。尽管如此，系统和高效 缺乏对AMR或新出现的病原体的这种治疗的开发。塔夫茨大学（Tufts University） 建设一个新的生物医学研究设施，实验室组合药物方案设计， 耐药和新兴病原体（LCDRD），设计和开发新的组合治疗方法 用于细菌、病毒、真菌和寄生虫感染，并加速对AMR和新出现的大流行病的研究 病原体LCDRD旨在促进难治性疾病的新型治疗方法的开发 来自动物和人类的病原体引起的感染。除了产生新的AMR疗法或 新出现的病原体，该设施将提供不同的，特征良好的人类细菌病原体与相关的 来自“塔夫茨医学”的临床数据，这是一个服务于不同人群的全州医院网络，用于研究 学术界和工业界。斯图尔特B。利维塔夫茨抗菌药物综合管理中心 阻力（CIMAR）联合来自TU和塔夫茨医学中心（TMC）的教师，以及来自 在整个地区和国家，在生物医学研究，工程，人类和兽医的专业知识， 医学、全球卫生、环境监测、政策和教育，以促进新的 治疗多种病原体的组合药物策略。在LCDRD中与CIMAR合作将是 新生的新发传染病和应对中心（CEIDAR），该中心负责处理新发和 不断扩大的传染病威胁，如昆虫传播的细菌和病毒病原体。CEIDAR包括 塔夫茨莱姆倡议，并利用BSL-3级塔夫茨新英格兰地区生物安全实验室（NERBL）， 塔夫茨卡明斯兽医学院在格拉夫顿，扩大工作的重要资源。机构 隶属于CIMAR/CEIDAR跨越学术和制药利益的范围，虽然位于 在TU本地，将加强区域和国家研究人员和实体之间的跨学科互动。 项目目标：LCDRD将使新兴和耐药微生物的专业化和协作工作成为可能。 这些病原体是产生新的组合治疗所需的。该设施将：1）加强互动 临床医生和生物医学研究人员之间的合作，以产生治疗性抗微生物药物方案，特别是 联合疗法，针对CDC紧急和新兴威胁病原体; 2）开发遗传和系统 为难以治疗的感染患者提供“个性化医疗”的方法; 3）提供空间 访问科学家可以在那里接受实践培训，从而在机构内传播知识， 在区域、国家和全球范围内; 4）提高国家应对传染病的能力 紧急情况下，通过提供学术和工业实体访问图书馆的良好特征的分离物， 新出现的大流行和AMR病原体。 受影响的空间和要求的设备：LCDRD将提供一个现代化的集中实验室， 多机构合作能力，利用最先进的研究技术， 并描述对当前治疗方案耐药的病原体的新型药物疗法以及新的 流行病威胁。它将为研究人员提供一个专门的生物安全环境， 耐药（MDR）和新出现的病原体。它将建在现有的2,400平方米。英尺壳层空间 生物医学研究和公共卫生大楼在塔夫茨健康科学校园在波士顿。新 设施，直接毗邻塔夫茨现有的BSL-3实验室和PI的实验室和一个关键的CIMAR研究员， 将由来自四所TU学校和TMC的跨学科研究人员团队以及合作者共享 其他区域和国家机构。 对研究和临床实践的影响：2019-2022年国家健康安全战略指出，“ 越来越多的AMR发生率具有公共卫生和国家安全后果”，“扩大 抗菌药物库是避免出现无法治愈的传染病时代的一个真实的迫切需要。” 通过集中和利用我们在细菌、病毒和MDR病原体方面的专业知识， 联合药物疗效和在耐药感染方面的深厚临床专业知识，LCDRD将 支持国家的AMR危机反应，通过产生新的疗法，无论是在塔夫茨和合作， 全国其他学术和制药实体（图1）。LCDRD将成为一个国家中心， 卓越，使广泛可用的良好表征的病原体与临床数据，允许链接， 菌株水平致病性和联合治疗的患者结局。这将使真正的链接从床边 一个反馈回路，将保持一个紧密的翻译重点，告知治疗方案， 当前和新出现的威胁，并促进个性化医疗。