Collaboration on HIV and AgingResearch through the Study of Mitochondria

摘要 孙静是约翰斯大学流行病学系的内科流行病学家和助理科学家。 霍普金斯大学彭博公共卫生学院。她寻求一个有指导的职业发展奖来填补知识 在她目前的培训中存在差距，使她能够发展成为一名独立的分子流行病学家 艾滋病毒流行病学、遗传学/表观遗传学和老龄化的不同领域，以改善 艾滋病毒携带者(PWH)。自从出现有效的抗逆转录病毒疗法以来， 威尔斯亲王中与年龄有关的情况。线粒体损伤是衰老的主要驱动因素，但它在艾滋病毒和艾滋病中的作用 衰老一直没有得到充分的研究。利用数据、基础设施和两种长期艾滋病毒的生物群落 队列(Alive和Mac)，孙博士将定义线粒体DNA拷贝数、a 线粒体含量的非侵入性标记，以及表型、分子和 艾滋病毒携带者和非艾滋病毒感染者的免疫学水平(目标1)。她将进一步定义 线粒体DNA拷贝数与DNA甲基化和核遗传学的关系 Mac(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，以评估 运动对PWH患者线粒体功能、甲基化模式和身体功能的影响。至 完成这些研究目标并制定独立的研究计划，孙博士将在 以下领域：(1)统计遗传学和多组学分析；(2)线粒体实验室测量 功能；(3)生物库和管理；(4)研究领导。培训计划由说教部分组成 课程和研讨会，统计遗传学分析实践，信息性实验室访问和 跟踪，参与证书计划，并由一个成熟和多样化的团队指导研究 高级调查员。拟议目标的完成将直接解决重要的流行病学问题， 机械性和干预性知识差距，并阐明线粒体功能在生物学上的作用 威尔斯亲王的老龄化。研究结果将为未来临床和干预研究的靶点提供证据 指导威尔斯亲王医院长期管理和提高生活质量的潜力。初步数据和 通过K01奖项建立的研究能力将支持R01研究线粒体功能的作用， 使用多组学方法研究威斯康星患者的衰老和合并症。它将进一步支持孙先生的长期 职业目标是成为艾滋病毒和老龄化领域的国际领导者，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.