Mentoring Research in Non-infectious Complications of HIV

HIV非感染性并发症的指导研究

• 批准号: 10490479
• 负责人: MICHAEL T YIN
• 金额: $ 18.86万
• 依托单位: COLUMBIA UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-09-17 至 2026-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10490479
• 关键词: AIDS clinical trial group; AIDS prevention; Adolescence; Advisory Committees; Anti-Retroviral Agents; Award; Biopsy; Biopsy Specimen; Bone structure; Brazil; Child; Clinical; Clinical Trials; Cohort Studies; Collaborations; Communicable Diseases; Competence; DNA Methylation; Data; Data Analyses; Databases; Education; Epidemiology; Evaluation; Fatty acid glycerol esters; Fracture; Future; Gene Expression; Genes; Goals; HIV; HIV Infections; HIV antiretroviral; HIV therapy; Hormones; Immunologic Markers; Impairment; In Vitro; Inflammation; Integrase; Interdisciplinary Study; Intervention; Investigation; Knowledge; LCN2 gene; Life; Longevity; Menopause; Mentors; Mentorship; Messenger RNA; Methylation; Midcareer Investigator Award in Patient-Oriented Research; Musculoskeletal; Needs Assessment; Osteoblasts; Osteocalcin; Osteogenesis; Osteoporosis; Outcome; Pathogenicity; Pathway interactions; Perinatal; Persons; Physiologic calcification; Play; Prevention; Process; Protease Inhibitor; Regimen; Research; Research Personnel; Resources; Risk; Role; Safety; Serum; Specialist; Specimen; Structure; Time; Tissues; Training; Universities; Woman; Women' s Interagency HIV Study; Work; Yin; aging population; antiretroviral therapy; base; biobank; bone; bone cell; bone health; bone imaging; bone loss; bone mass; bone metabolism; bone strength; career; comorbidity; design; dimensional analysis; epigenome; epigenome-wide association studies; experience; fracture risk; high dimensionality; imaging biomarker; inhibitor; insight; interest; investigator training; lipid metabolism; multidimensional data; multidisciplinary; next generation; novel; novel marker; older men; older women; osteogenic; patient oriented research; perinatal HIV; personalized approach; programs; skeletal; transcriptomics; translational study; young adult

Abstract The goals of this application for a K24 midcareer investigator award in patient-oriented research (POR) are to allow me to devote more time to augment capabilities in POR with a focus on non-infectious complications of HIV, and provide mentorship to junior investigators. With an aging population of people with HIV (PWH), research on prevention and management of non-infectious complications of HIV will continue to increase in importance. I am an infectious diseases specialist trained in epidemiology whose research has primarily focused on elucidating the impact of HIV and antiretroviral therapy (ART) on bone health. I have established multidisciplinary collaborations over the last 15 years to evaluate the epidemiology of bone loss, osteoporosis and fractures in PWH, determine the impact of perinatal HIV on bone acquisition and peak bone mass, and perform clinical trials to mitigate bone loss with ART. I have also led translational studies using novel imaging and biomarkers to investigate pathogenic mechanisms; however, these mechanisms are still not completely understood, largely due to lack of tissue-based studies. Biospecimens from recently completed studies, including the comprehensive first bone biopsy study of PWH before and after ART initiation and a study of women undergoing the menopausal transition (RO1 AI095089) provide new opportunities for mechanistic insights. The Specific Aims of the Research Plan are to: (1) investigate the pathophysiologic underpinnings of impaired bone formation associated with HIV and ART through transcriptomic analysis of bone biopsies; (2) delineate the role of bone-derived hormones on fat gain with ART initiation, (3) evaluate associations between DNA methylation signatures and osteoporosis in women with HIV. Each Aim is designed specifically to augment the training of junior investigators. The K24 provides me opportunity for formal training in high dimensional data analyses and mentored experiential training with the proposed epigenome analyses. A central component of my mentoring program is an individualized approach to training, which includes a needs assessment of core research competencies and an ongoing evaluation process. I will draw upon the superb resources and multidisciplinary expertise at Columbia University and within HIV research networks that I have worked in throughout my career, especially the MACS/WIHS Combined Cohort Study and the AIDS Clinical Trials Group. In addition, a Mentor Advisory Committee consisting of experienced leaders in POR and education at Columbia University will guide me in building a structured and sustainable mentoring program to develop the next generation POR investigators in HIV research.

抽象的 该申请授予K24中级护理研究员奖的目标是以患者为导向的研究（POR） 请允许我花更多的时间来增强POR的能力，重点是非感染并发症 艾滋病毒，并为初级调查人员提供指导。患有艾滋病毒（PWH）的人口老龄化，研究 关于预防和管理非感染艾滋病毒并发症的重要性将继续提高重要性。我 是经过流行病学培训的传染病专家，其研究主要集中于阐明 艾滋病毒和抗逆转录病毒疗法（ART）对骨骼健康的影响。我已经建立了多学科 在过去的15年中，合作评估骨质流失，骨质疏松和骨折的流行病学 PWH，确定围产期艾滋病毒对骨习得和峰值骨量的影响，并进行临床试验 通过艺术减轻骨质流失。我还使用新成像和生物标志物领导了翻译研究 研究致病机制；但是，这些机制仍然尚未完全理解，在很大程度上 由于缺乏基于组织的研究。来自最近完成的研究的生物测量，包括综合 ART启动之前和之后的PWH的首次骨活检研究以及对经历绝经的妇女的研究 过渡（RO1 AI095089）为机械见解提供了新的机会。研究的具体目的 计划要：（1）研究与HIV相关的骨形成受损的病理生理基础 通过对骨活检的转录组分析和艺术； （2）描述骨衍生激素在 脂肪随着艺术的启动而获得的脂肪，（3）评估DNA甲基化特征与骨质疏松症之间的关联 艾滋病毒的妇女。每个目标都是专门设计的，旨在增加对初级调查人员的培训。 K24 为我提供了在高维数据分析和指导体验培训中进行正式培训的机会 提出的表观基因组分析。我的指导计划的一个核心部分是个性化的 培训方法，其中包括对核心研究能力的需求评估和持续的 评估过程。我将利用哥伦比亚大学的精湛资源和多学科专业知识 在我整个职业生涯中一直在艾滋病毒研究网络中，尤其是Mac/Wihs 队列研究和艾滋病临床试验组。此外，一个导师咨询委员会组成 哥伦比亚大学经验丰富的POR和教育领导者将指导我建立一个结构化和 可持续的指导计划旨在开发艾滋病毒研究中的下一代POR研究者。