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.

（一）概述 过去两年的情况表明，传染病是全球性威胁，迫切需要改进 做好对抗未知病原体的准备。此外，由以下原因引起的感染病例数量惊人地增加： 近年来，抗生素耐药性（AMR；见下文词汇表）病原体的出现因 COVID-19 的爆发而加剧 大流行表明，我们也正处于失去治疗由已知病毒引起的感染的能力的边缘 病原体。联合药物治疗是治疗由以下原因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。仍然系统、高效 针对 AMR 或新出现病原体的此类治疗方法尚缺乏开发。塔夫茨大学（TU）提议 建造一个新的生物医学研究设施，组合药物方案设计实验室 耐药和新兴病原体（LCDRD），设计和开发新的组合治疗方法 针对细菌、病毒、真菌和寄生虫感染，并加速对抗菌素耐药性和新出现的流行病的研究 病原体。 LCDRD 旨在促进难以治疗的新疗法的开发 由动物和人类病原体引起的感染。除了针对 AMR 或 针对新兴病原体，该设施将提供多样化、特征明确的人类细菌病原体，并与相关 来自“塔夫茨医学”（服务不同人群的全州医院网络）的临床数据供研究 受到学​​术界和工业界的关注。 Stuart B. Levy 塔夫茨抗菌药物综合管理中心 阻力 (CIMAR) 联合了来自 TU 和塔夫茨医学中心 (TMC) 的教职人员以及来自 跨地区和国家，拥有生物医学研究、工程、人类和兽医方面的专业知识 医学、全球健康、环境监测、政策和教育，以促进新领域的发展 治疗多种病原体的组合药物策略。在 LCDRD 中与 CIMAR 合作将是 新兴传染病和应对中心（CEIDAR），致力于解决新发传染病和 不断扩大的传染病威胁，例如虫媒细菌和病毒病原体。 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) 位于格拉夫顿的塔夫茨卡明斯兽医学院是扩大工作的重要资源。机构 隶属于 CIMAR/CEIDAR，涵盖一系列学术和制药领域，尽管位于 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 将促进针对新兴和耐药微生物的专业化和协作性工作 产生新的组合治疗所需的病原体。该设施将：1）增强互动 临床医生和生物医学研究人员之间的合作，以制定治疗性抗菌药物方案，特别是 针对疾病预防控制中心紧急和新出现的威胁病原体的联合疗法； 2）开发遗传和系统 为患有难以治疗的感染的患者提供“个性化医疗”的方法； 3）提供空间 访问科学家可以在这里接受实践培训，从而在机构内传播知识， 区域、国家和全球； 4) 提高国家应对传染病的能力 为学术和工业实体提供充分表征的菌株库的访问权限，以应对紧急情况 新出现的流行病和抗菌素耐药性病原体。 受影响的空间和所需设备：LCDRD 将提供一个现代化的集中实验室和 多机构努力的协作能力，利用最先进的研究技术来产生 并描述针对对当前治疗方案耐药的病原体的新药物疗法以及新疗法 大流行的威胁。它将为研究人员提供一个专业的、生物安全的环境，以便与多方合作 耐药性（MDR）和新出现的病原体。它将建在现有的 2,400 平方英尺的外壳空间内 波士顿塔夫茨健康科学园区的生物医学研究和公共卫生大楼。新的 设施，直接毗邻塔夫茨大学现有的 BSL-3 实验室以及 PI 和 CIMAR 关键研究员的实验室， 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 来自其他区域和国家机构。 对研究和临床实践的影响：《2019-2022 年国家卫生安全战略》指出，“ 抗菌素耐药性发生率的不断上升对公共卫生和国家安全都产生了影响”，并且“扩大了抗菌素耐药性的范围” 抗菌库是避免无法治疗的传染病时代的真正而紧迫的要求。” 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，创新措施 LCDRD 凭借组合药物疗效以及耐药性感染方面深厚的临床专业知识， 通过在塔夫茨大学和与其他机构合作开发新疗法来支持国家的抗菌药物耐药性危机应对 全国其他学术和制药实体（图 1）。 LCDRD将成为国家中心 卓越的性能使广泛可用的、具有良好特征的病原体与临床数据相结合，从而能够将 菌株水平致病性和联合治疗的患者结果。这将实现床边的真正链接 替补和后退——一个反馈循环，将保持紧密的转化焦点，为治疗方案提供信息 当前和新出现的威胁，并促进个性化医疗。