Collaboration on HIV and AgingResearch through the Study of Mitochondria

点击翻译按钮获取中文摘要

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.