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

基本信息

批准号：
10450089
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
项目类别：
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/10450089
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 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

项目摘要

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 博士是一位传染病医师兼科学家，在指导研究人员方面拥有丰富的经验与 HIV-1 治愈和根除相关的备受瞩目的、以患者为导向的研究。以患者为中心的多种研究计划，包括分子和细胞免疫学研究利用患者来源的细胞、转化人体研究和旨在探索的介入性临床试验这些研究活动提供了减少 HIV-1 病毒库的新治疗方法。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过去，他的几位学员和同事已经对 HIV-1 感染进行了功能性或绝育治疗；取得了 R 级资助，并获得了高度选择性的独立教职职位在拟议的 K24 申请中，Lichterfeld 博士将扩展和拓展他的研究领域。在三个前沿研究领域的成功指导活动：他将指导以下领域的学员旨在探索新颖的介入性临床试验的概念化、设计、实施和进行根除 HIV-1 的治疗策略（具体目标 1）。正在进行的由 NIAID 资助的临床试验，Lichterfeld 博士担任 PI，但未来将扩大将新颖的想法和概念转化为探索性、概念验证的临床试验。先进的临床试验研究基础设施和积极主动的 HIV-1 患者群体的优势布莱根妇女医院和麻省总医院，这两家医院 Lichterfeld 博士此外，Lichterfeld 博士还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、近全长病毒测序以及病毒整合位点分析、染色质可及性测定和染色质免疫沉淀测定来分析患者来源的细胞样本中残留病毒库的范围前所未有（具体目标 2）。拉根研究所独特的技术资源和跨学科合作将促进麻省理工学院和哈佛大学博德研究所，Lichterfeld 博士拥有该研究所的准会员身份。 Lichterfeld 将提供儿童 HIV-1 感染方面的独特培训经验，重点关注儿童 HIV-1 感染的发展可能使博茨瓦纳新生儿的 HIV-1 感染长期、无药物缓解的干预措施（具体目标 3）。这些合作调查将在 NIAID 资助的持续背景下进行。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的临床试验 HIV-1 感染婴儿在开始治疗后的最初几天内发现病毒库和抗病毒免疫反应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、创造力和协作以患者为导向的研究重点是寻找 HIV-1 感染的治疗方法。