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: 10258715
• 负责人: Mathias Lichterfeld
• 金额: $ 19.01万
• 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/10258715
• 关键词: Address; Adherence; Adult; Antigens; Antiviral Agents; 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; Institutes; Institution; Interruption; Intervention; Intervention Studies; Investigation; Knowledge; 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; 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; virology

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.

抽象的 Lichterfeld博士是一种感染性疾病身体科学家，在心理研究中有很强的记录 与HIV-1治愈和消除有关的高调，面向患者的研究。他进行了广泛的 包括分子和细胞免疫学研究的患者研究的多样化研究计划 随着患者衍生的细胞，翻译的人类研究和旨在探索的介入临床试验 减少HIV-1储层的新型治疗方法。这些研究活动提供了吸引力， 为医师和科学家感兴趣并投资于制定策略的激动人心的培训机会 HIV-1感染的功能或灭菌治疗；过去，他的几个梅内斯和委托人 进步以获得R级资金，并获得了高度选择性的独立教师职位 世界各地的大学。在拟议的K24申请中，Lichterfeld博士将扩展并扩展他的 在三个尖端研究领域的背景下，成功的心理活动：他将在智力学员中 旨在探索新颖的概念化，设计，实施和进行介入的临床试验 消除HIV-1的治疗策略（特定目的1）。这些活动最初将集中于 Lichterfeld博士作为PI的持续，NIAID资助的临床试验，但将来会扩展 将新颖的思想和概念转化为探索性概念验证临床试验。这些研究进行 高级临床试验研究基础设施的优势和高度动机的HIV-1患者人群 两家医院Lichterfeld博士 与。此外，Lichterfeld博士将培训他的受训者的创新下一代测序和 涉及单基因组的蛋白质组学方法接近全长病毒测序，并结合病毒 集成站点分析，染色质可及性测定和染色质免疫沉淀测定法 在空前的宽度上，在患者来源的细胞样品中残留病毒储量（特定目标2）。这项工作 将由Ragon Institute的独特技术资源和跨学科合作准备 麻省理工学院和哈佛大学的广泛研究所，利希特菲尔德博士在那里拥有副成员身份。最后，博士 Lichterfeld将在儿科HIV-1感染方面提供独特的培训经验，重点是 可以从博茨瓦纳的新生儿中长期无毒的HIV-1感染的干预措施 （特定目标3）。这些协作调查将在持续的，由NIAID资助的背景下进行 临床试验研究标准抗逆转录病毒疗法和广泛中和抗体对病毒的影响 HIV-1感染的婴儿的储层和抗病毒免疫反应在后的头几天开始接受治疗 生日。这些研究共同为医生和科学家提供了独特但相互关联的培训机会 获得独立职业所需的知识，技能，创造力和合作 以患者为导向的研究着重于寻找HIV-1感染的治疗方法。