Mentoring Investigators in HIV and Tuberculosis Therapeutics Research

指导艾滋病毒和结核病治疗研究的研究人员

• 批准号: 10729712
• 负责人: Kelly E. Dooley
• 金额: $ 6.55万
• 依托单位: VANDERBILT UNIVERSITY MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-02-21 至 2026-01-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10729712
• 关键词: Mentoring; Investigators; HIV; Tuberculosis; Therapeutics

SUMMARY Tuberculosis (TB) is now the leading infectious cause of death globally, and it remains the #1 cause of death among people living with HIV (PLWH). The first-line regimen is long and burdensome to patients and programs, and drug-resistant TB typically requires treatment for 1-2 years with drugs that can cause severe or irreversible toxicities. The TB drug development pipeline is now robust, providing reason for optimism. To optimize current and new drugs, though, we must employ state-of-the-art drug development approaches (including best use of quantitative pharmacology), and it is imperative that new drugs or regimens be developed so that they can be used in all patients that may benefit from them, including PLWH, children, and pregnant women. Critical challenges and opportunities lie in using clinically pharmacology as a tool more effectively in TB and HIV therapeutics research, across the drug development and optimization spectrum. This is the context for this application for a K24 Mid-Career Development Award for Kelly Dooley, MD, PhD, Associate Professor of Medicine, Pharmacology, & Molecular Sciences in the Divisions of Clinical Pharmacology and Infectious Diseases at Johns Hopkins University, to provide protected time to mentor trainees in patient-oriented research in TB and HIV therapeutics. Dr. Dooley is one of the few Infectious Diseases specialists with training in Clinical Pharmacology working in the TB therapeutics field. She is a globally-recognized leader in TB and HIV- associated TB treatment research and has mentored (and is mentoring) multiple trainees in the field. Through the multiple independently-funded studies she is leading as well as those she is directing in her capacity as a member of the TB scientific leadership committees of the ACTG, TBTC, and IMPAACT networks, she is in a position to provide excellent opportunities to train the next generation of clinical researchers in patient-oriented research in TB and HIV. In addition, this K24 will allow her to expand her own knowledge in several key areas: quantitative pharmacology approaches, as applied to design and analysis in clinical trials of TB or TB-HIV treatment; biomarkers identification and use as well as understanding of drug delivery to hard-to-access compartments, for example in tuberculous meningitis; and a new area of critical unmet medical need, the treatment of nontuberculous mycobacteria (in patients with and without HIV). This K24 will allow Dr. Dooley to have the protected time to train the next generation of investigators in clinical pharmacology and clinical research, as applied to TB and HIV- associated TB, a critical shortage area; expand quantitative approaches in TB therapeutics work; and explore new areas of investigation. The protected time afforded by this award is essential to Dr. Dooley achieving these goals.

概括 结核病 (TB) 目前是全球主要的传染性死亡原因，并且仍然是导致死亡的第一大原因 艾滋病毒感染者（PLWH）的死亡。一线治疗方案时间长，给患者带来负担 和计划，耐药结核病通常需要使用可导致耐药性的药物治疗 1-2 年。 严重或不可逆的毒性。结核病药物开发渠道现在很强大，这为我们提供了理由 乐观。然而，为了优化现有药物和新药物，我们必须采用最先进的药物 开发方法（包括定量药理学的最佳利用），并且必须采用新的方法 开发药物或治疗方案，以便它们可以用于所有可能从中受益的患者， 包括艾滋病病毒感染者、儿童和孕妇。关键的挑战和机遇在于使用 临床药理学作为结核病和艾滋病毒治疗研究中更有效的工具，涵盖整个药物 开发和优化范围。这是 K24 职业生涯中期申请的背景 凯利·杜利 (Kelly Dooley) 医学博士、哲学博士、医学、药理学副教授和 约翰霍普金斯大学临床药理学和传染病部门的分子科学 大学为受训者提供受保护的时间，指导他们进行以患者为中心的结核病和艾滋病毒研究 疗法。杜利博士是少数接受过临床培训的传染病专家之一 结核病治疗领域的药理学工作。她是全球公认的结核病和艾滋病毒领域的领导者 相关的结核病治疗研究，并已指导（并且正在指导）该领域的多名学员。 通过她领导的多项独立资助的研究以及她在她的研究中指导的研究 作为 ACTG、TBTC 和 IMPAACT 结核病科学领导委员会成员 网络，她能够提供绝佳的机会来培训下一代临床医生 结核病和艾滋病毒以患者为导向的研究人员。此外，这台 K24 将使她能够扩展自己的能力 自己在几个关键领域的知识：定量药理学方法，应用于设计和 结核病或结核病艾滋病治疗的临床试验分析；生物标志物的识别和使用以及 了解药物输送到难以进入的隔室，例如结核性脑膜炎； 以及一个未满足的关键医疗需求的新领域，即非结核分枝杆菌的治疗（在 感染和未感染艾滋病毒的患者）。这台 K24 将使 Dooley 博士有受保护的时间来训练下一个 临床药理学和临床研究领域的研究者的产生，应用于结核病和艾滋病毒- 相关结核病，严重短缺领域；扩大结核病治疗工作的定量方法；和 探索新的调查领域。该奖项提供的受保护时间对杜利博士至关重要 实现这些目标。