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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.

摘要