Mentoring in patient-oriented research to finding a cure for HIV-1 infection

指导以患者为导向的研究，寻找 HIV-1 感染的治疗方法

• 批准号: 10669009
• 负责人: Mathias Lichterfeld
• 金额: $ 19.21万
• 依托单位: BRIGHAM AND WOMEN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-07-13 至 2026-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10669009
• 关键词: Address; Adherence; Adult; Antigens; Area; Basic Science; Bioinformatics; Biological Assay; Birth; Botswana; Cells; Cellular Immunology; Characteristics; Childhood; Chromatin; Clinic; Clinical; Clinical Medicine; Clinical Research; Clinical Sciences; Clinical Trials; Clinical Trials Design; Collaborations; Communicable Diseases; Communities; Complement; Complex; Conduct Clinical Trials; Consensus; Creativeness; Development; Disease; Disease remission; Doctor of Philosophy; Educational workshop; Epigenetic Process; Evolution; Faculty; Funding; Future; General Hospitals; Genetic; Genetic Transcription; Genome; HIV; HIV-1; Home; Hospitals; Hour; Human; Immune response; Immune system; Immunologics; Individual; Infant; Infection; Institution; Interruption; Intervention; Intervention Studies; Investigation; Investments; Knowledge; Knowledge acquisition; Laboratory Research; Length; Life; Life Expectancy; Massachusetts; Mentors; Mentorship; Molecular; Molecular Immunology; Monitor; National Institute of Allergy and Infectious Disease; Neonatal; Patients; Persons; Pharmaceutical Preparations; Physicians; Positioning Attribute; Predisposition; Principal Investigator; Procedures; Proteomics; Research; Research Activity; Research Infrastructure; Research Personnel; Research Project Grants; Residual state; Resources; Retrovirology; Sampling; Scientist; Subgroup; Systems Biology; Techniques; Technology; Therapeutic Intervention; Time; Training; Training Programs; Translating; Translational Research; United States National Institutes of Health; Universities; Viral; Viral Load result; Viral reservoir; Virus Diseases; Virus Integration; Woman; Work; antiretroviral therapy; biocomputing; bridge program; career; chromatin immunoprecipitation; clinical care; design; experience; genome analysis; global health; improved; infant infection; innovation; integration site; interest; member; multidimensional data; neonatal infection; neonate; neutralizing antibody; new technology; next generation; next generation sequencing; novel; novel therapeutic intervention; patient oriented; patient oriented research; patient population; pediatric human immunodeficiency virus; programs; protocol development; research study; skills; therapy development; training opportunity

Abstract Dr. Lichterfeld is an infectious disease physician-scientist with a strong record of mentoring research fellows in high-profile, patient-oriented research studies related to HIV-1 cure and eradication. He conducts a broad and diverse research program of patient-oriented studies that include molecular and cellular immunologic studies with patient-derived cells, translational human investigations and interventional clinical trials designed to explore novel therapeutic approaches to reduce HIV-1 reservoirs. These research activities provide attractive and exciting training opportunities for physicians and scientists interested and invested in developing strategies for a functional or sterilizing cure for HIV-1 infection; in the past, several of his mentees and co-mentees have progressed to receive R-level funding, and have been offered independent faculty positions at highly-selective universities around the world. In the proposed K24 application, Dr. Lichterfeld will extend and expand his successful mentoring activities in the context of three cutting-edge research areas: He will mentor trainees in the conceptualization, design, implementation and conduct of interventional clinical trials designed to explore novel therapeutic strategies for HIV-1 eradication (Specific Aim 1). These activities will initially focus on an already ongoing, NIAID-funded clinical trial in which Dr. Lichterfeld serves as the PI, but will be expanded in the future to translate novel ideas and concepts into exploratory, proof-of-concept clinical trials. These studies take advantage of advanced clinical trial research infrastructure and a highly motivated HIV-1 patient population at the Brigham and Women’s Hospital and the Massachusetts General Hospital, the two hospitals Dr. Lichterfeld is affiliated with. In addition, Dr. Lichterfeld will train his mentees in innovative next-generation sequencing and proteomics approaches involving single-genome, near full-length viral sequencing, combined with viral integration site analysis, chromatin accessibility assays and chromatin immunoprecipitation assays to profile residual viral reservoirs in patient-derived cell samples at an unprecedented breadth (Specific Aim 2). This work will be facilitated by unique technical resources and cross-disciplinary collaborations at the Ragon Institute and the Broad Institute of MIT and Harvard, where Dr. Lichterfeld holds Associate Member status. Finally, Dr. Lichterfeld will offer a distinct training experience in pediatric HIV-1 infection, focusing on the development of interventions that may enable a long-term, drug free remission of HIV-1 infection in neonates from Botswana (Specific Aim 3). These collaborative investigations will be performed in the context of ongoing, NIAID-funded clinical trials investigating effects of standard antiretroviral therapy and broadly-neutralizing antibodies on viral reservoirs and antiviral immune responses in HIV-1-infected infants started on therapy within the first days after birth. Together, these studies provide distinct but interrelated training opportunities for physicians and scientists to acquire the knowledge, skills, creativity and collaborations that are needed for an independent career in patient-oriented studies focused on finding a cure for HIV-1 infection.

摘要 利希特菲尔德博士是一位传染病内科医生兼科学家，在指导研究人员方面有很好的记录 与治愈和根除艾滋病毒-1有关的备受瞩目的、以患者为中心的研究。他主持了一场广泛的 各种以患者为中心的研究计划，包括分子和细胞免疫学研究 通过患者来源的细胞，转化性人类研究和干预性临床试验旨在探索 减少HIV-1宿主的新治疗方法。这些研究活动提供了有吸引力和 为有兴趣并投资于制定战略的医生和科学家提供令人兴奋的培训机会 HIV-1感染的功能性或灭菌性治疗；在过去，他的几名学员和共同学员 获得了R级资助，并获得了高度挑剔的独立教员职位 世界各地的大学。在提议的K24应用程序中，Lichterfeld博士将扩展和扩展他的 在三个前沿研究领域的背景下成功的指导活动：他将在 旨在探索新事物的介入临床试验的概念化、设计、实施和实施 根除艾滋病毒-1的治疗战略(具体目标1)。这些活动最初将重点放在已经 正在进行的由NIAID资助的临床试验，Lichterfeld博士担任PI，但未来将扩大 将新的想法和概念转化为探索性的、概念验证的临床试验。这些研究需要 先进的临床试验研究基础设施和高度积极的HIV-1患者群体的优势 布里格姆妇女医院和马萨诸塞州综合医院，这两家医院利希特菲尔德博士 隶属于。此外，利希特菲尔德博士将培训他的学员进行创新的下一代测序和 蛋白质组学方法涉及单基因组、接近全长的病毒测序，与病毒相结合 整合位点分析、染色质可及性分析和染色质免疫沉淀分析 患者来源细胞样本中的残留病毒库达到前所未有的广度(具体目标2)。这部作品 将通过独特的技术资源和拉贡研究所的跨学科合作来促进 麻省理工学院和哈佛大学博德研究所，利希特菲尔德博士在那里拥有准会员身份。最后，戴维斯博士说。 Lichterfeld将在儿童HIV-1感染方面提供独特的培训经验，重点是发展 干预措施可以使博茨瓦纳新生儿的HIV-1感染得到长期、无药物的缓解 (具体目标3)。这些合作调查将在NIAID资助的持续进行的背景下进行 标准抗逆转录病毒治疗和广谱中和抗体对病毒影响的临床试验 HIV-1感染婴儿的宿主和抗病毒免疫反应在治疗后的头几天内开始治疗 出生。总之，这些研究为医生和科学家提供了截然不同但相互关联的培训机会 获得独立职业生涯所需的知识、技能、创造力和协作能力 以患者为中心的研究集中在寻找治疗HIV-1感染的方法上。