Collaboration on HIV and AgingResearch through the Study of Mitochondria

摘要 孙静是约翰·霍普金斯大学流行病学系的流行病学家和助理科学家 霍普金斯布隆伯格公共卫生学院。她寻求一个指导职业发展奖，以填补知识 在她目前的培训差距，使她发展成为一个独立的分子流行病学家谁可以桥梁 艾滋病毒流行病学、遗传学/表观遗传学和老龄化等不同领域，以改善艾滋病毒感染者的长期结局。 艾滋病毒感染者（PWH）。自从有效的抗逆转录病毒疗法出现以来， 威尔斯亲王医院与老化有关的情况。线粒体损伤是衰老的主要驱动力，但它在艾滋病毒和 衰老还没有被充分研究。利用数据、基础设施和两种长期艾滋病毒的生物标本 研究组（ALIVE和MACS）中，孙博士将定义线粒体DNA拷贝数、 线粒体含量的非侵入性标志物，以及表型、分子和 艾滋病毒感染者和非感染者的免疫水平（目标1）。她将进一步确定 线粒体DNA拷贝数与DNA甲基化和核遗传学使用现有数据从ALIVE和 MACS（目标2）。在目标3中，她将设计一项嵌套在正在进行的运动干预试验中的研究， 运动对PWH中线粒体功能、甲基化模式和身体功能的影响。到 完成这些研究目标并制定独立的研究计划，孙博士将接受培训， 以下领域：（1）统计遗传学和多组学分析;（2）线粒体的实验室测量 功能;（3）生物库和管理;（4）研究领导。培训计划包括教学 课程和研讨会，统计遗传学分析的实践，信息实验室访问， 影子，参加证书课程，并由一个成熟的和多样化的团队指导研究， 资深调查员实现拟议目标将直接解决重要的流行病学问题， 机制和干预性知识差距，并阐明线粒体功能在生物学中的作用。 PWH中的老化。研究结果将为未来的临床和干预性研究提供证据， 指导威尔斯亲王医院的长期管理和改善生活质量的潜力。初步数据和 通过该K 01奖项建立的研究能力将支持R 01研究线粒体功能的作用， 老化和PWH中的共病使用多组学方法。它将进一步支持孙博士的长期 职业目标：成为HIV和衰老领域的国际领导者，拥有线粒体遗传学方面的专业知识 和功能

ABSTRACT Jing Sun is a physician epidemiologist and Assistant Scientist in the Department of Epidemiology at Johns Hopkins Bloomberg School of Public Health. She seeks a mentored career development award to fill knowledge gaps in her current training, allowing her to develop as an independent molecular epidemiologist who can bridge the diverse fields of HIV epidemiology, genetics / epigenetics, and aging to improve long-term outcomes among people with HIV (PWH). Since the advent of effective antiretroviral therapy, there has been a rising burden of aging-related conditions among PWH. Mitochondrial damage is a major driver of aging, but its role in HIV and aging has been understudied. Leveraging data, infrastructure, and the biospecimens of two long-term HIV cohorts (ALIVE and MACS), Dr. Sun will define the relationship between mitochondrial DNA copy number, a noninvasive marker of mitochondrial content, and biological aging at the phenotypic, molecular, and immunological levels among people with and without HIV (Aim 1). She will further define the interrelationship of mitochondrial DNA copy number with DNA methylation and nuclear genetics using existing data from ALIVE and MACS (Aim 2). In Aim 3, she will design a study nested within an ongoing exercise intervention trial to evaluate the effect of exercise on mitochondrial function, methylation patterns, and physical function among PWH. To complete these research aims and develop an independent research program, Dr. Sun will receive training in the following areas: (1) statistical genetics and multi-omics analysis; (2) laboratory measurement of mitochondrial function; (3) biobanking and management; (4) research leadership. The training program consists of didactic coursework and seminars, hands-on practice in statistical genetics analysis, informational laboratory visits and shadowing, participation in a certificate program, and mentored research by an established and diverse team of senior investigators. Completion of the proposed aims will directly address important epidemiological, mechanistic, and interventional knowledge gaps and elucidate the role of mitochondrial function on biological aging among PWH. Findings will provide evidence for targets of future clinical and interventional research with the potential to guide long-term management and improve quality of life among PWH. Preliminary data and research capacity built through this K01 award will support an R01 investigating the role of mitochondrial function, aging, and comorbidities among PWH using a multi-omics approach. It will further support Dr. Sun’s long-term career goals to become an international leader in HIV and aging with content expertise in mitochondrial genetics and function.