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 过去两年表明，受感染的疾病是全球威胁，表明迫切需要改善 准备对抗未知病原体。此外，由 近年来，抗菌素耐药性（AMR；请参见下面的词汇表，下面）病原体。 大流行，说明我们也处于失去治疗因素感染的能力的边缘 病原体。联合药物治疗是治疗由 几种微生物病原体，包括HIV和结核菌细菌。尽管如此，系统性和高效 缺乏为AMR或新兴病原体的这种治疗方法的开发。塔夫茨大学（TU）提议 为了构建一种新的生物医学研究设施，组合药物方案设计实验室 抗性和新兴病原体（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和新兴大流行的研究 病原体。 LCDR旨在促进用于难以治疗的新型治疗 由于动物和人类的病原体引起的感染。除了为AMR生成新疗法或 新兴病原体，该设施将提供潜水员，良好的人类细菌病原体 来自“塔夫茨 - 医学”的临床数据，这是一个为潜水员人群提供服务的医院范围内的网络 由学术界和工业。 Stuart B. Levy Tuft抗菌综合管理中心 TU和TUFTS医疗中心（TMC）的阻力（CIMAR）单位，以及来自的会员 在整个地区和国家，具有生物医学研究，工程，人类和兽医方面的专业知识 医学，全球健康，环境监视，政策和教育，以促进新的发展 组合药物策略治疗多种病原体。在LCDRD与CIMAR合作将是 新兴传染病和反应（CEIDAR）的新生中心，该中心解决了新兴和 不断扩大传染病威胁，例如绝缘细菌和病毒病原体。 CEIDAR包括 塔夫茨莱姆（Tufts Lyme）倡议并利用BSL-3级簇 格拉夫顿（Grafton）的塔夫茨·卡明斯（Tufts Cummings）兽医学院，这是扩大工作的重要资源。机构 与Cimar/Ceidar相关 在TU的本地，将增强区域和国家调查人员和实体之间的跨学科互动。 项目目标：LCDRD将实现有关新兴和抵抗微生物的专业和协作工作 生成新组合治疗所需的病原体。设施将：1）增强互动 在临床医生和生物医学研究人员之间生成治疗性抗菌药物方案，特别是 结合疗法，针对CDC紧急和新兴的威胁病原体； 2）发展遗传和系统 为难以治疗感染的患者促进“个性化医学”的方法； 3）提供一个空间 来访的科学家可以接受动手培训，从而使知识在机构内部传播， 在地区，全国和全球范围内； 4）提高国家对传染病的反应能力 通过为学术和工业实体提供进入特征良好的分离株图书馆的紧急情况 新兴的大流行和AMR病原体。 受影响的空间和要求的设备：LCDRD将提供现代的集中实验室，并 多机构努力利用最先进的研究技术来生成的协作能力 并表征了抗当前治疗方案的病原体的新型药物疗法以及新的药物疗法 大流行威胁。它将为研究人员提供专门的生物保护环境 耐药性（MDR）和新兴病原体。它将在现有的2,400平方英尺的外壳空间中构建 波士顿塔夫茨健康科学校园的生物医学研究和公共卫生大楼。新的 设施，直接与Tufts现有的BSL-3实验室和PI实验室和CIMAR研究员的实验室相邻的设施， 来自四所TU学校和TMC的跨学科研究人员团队以及合作者将共享 来自其他地区和国家机构。 对研究和临床实践的影响：2019 - 2022年国家健康安全战略，“ 不断增长的AMR事件既具有公共卫生和国家安全后果”，并且“扩大了 抗菌武器是避免不可治疗的传染病时代的真实和直接要求。” 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 联合药物效率和对治疗性感染的深层临床专业知识，LCDRD将 通过在塔夫特和与 全国其他学术和药品实体（图1）。 LCDRD将成为国家中心 卓越的临床数据使广泛可用的病原体可用，从而可以联系 患者对应变水平的致病性和组合疗法的结果。这将使床边的真实链接 到板凳和背部 - 一个反馈循环，将保持紧密的翻译重点，告知治疗方案 当前和新兴的威胁，并促进个性化医学。