CANDIDATE: The candidate's long-term career goal is to become an independent researcher and mentor with expertise in using metabolomics, and other emerging technologies, to improve understanding of health in aging, including cardiovascular disease etiology, prevention and treatment. Her short-term goals for this K01 award build upon her current experience in epidemiology of aging research and general molecular epidemiology. Specifically, she will: (1) develop expertise in the epidemiology and pathophysiology of cardiovascular disease; (2) expand knowledge of metabolomics and systems science, and gain exposure to statistical methodology for -omics research; and (3) expand expertise in data collection. The candidate's plan for realizing these goals includes 4 years of research; coursework in cardiovascular epidemiology, systems science, and biostatistics; mentored training, consisting of mentorship in cardiovascular epidemiology and pathophysiology, hypertension, data collection, and statistical methods for analysis of metabolomics data; and participation in relevant local research groups, seminars, and national professional meetings. The training plan also includes activities focused on general career development, including mentored training, grant writing tutorials, responsible conduct of research courses, and programs on research leadership, effective mentoring, and communication. ENVIRONMENT: The proposed training would take place at the Channing Division of Network Medicine at Brigham and Women's Hospital and Harvard Medical School, an institution with a strong base of epidemiologic research in novel biomarkers of cardiovascular disease. Brigham and Women's Hospital is closely affiliated with Harvard School of Public Health as well as the other Harvard-affiliated schools and hospitals, providing ample opportunities for intellectual interactions, including seminars, working groups, and numerous course offerings. The Hospital has provided the candidate with the necessary computing resources, including internet and research software, and access to the cohort datasets she will need to complete the research aims. RESEARCH: Two-thirds of adults aged 60 years and older in the United States have hypertension, which is associated with increased risks of heart disease, stroke, and kidney disease, and is estimated to be the single greatest underlying cause of non-communicable mortality worldwide. The vast majority of hypertension does not have an identifiable cause and likely results from complex interactions between multiple genetic and environmental factors. Identification of new biomarkers to improve our understanding of hypertension etiology could inform potential strategies for prevention and risk reduction. Metabolomics, which allows quantification of small-molecule metabolites that represent the ultimate downstream product of gene and environment interactions, may be a promising approach to better elucidate hypertension pathogenesis. Thus, for this K01 application, the candidate proposes to study metabolites related to endothelial dysfunction, a likely mechanism involved in blood pressure dysregulation, and risk of new hypertension diagnosis over 14 years, leveraging existing data on plasma metabolomics, hypertension, and relevant covariates from 940 adults enrolled in 3 ongoing cohort studies that use biennial questionnaires to prospectively collect information on participants' medical history and lifestyle. She will also investigate whether identified metabolits mediate associations of established risk factors (adiposity, physical activity, diet) with new hypertension diagnosis. In addition, both to gain experience in new data collection and to explore more detailed biologic relations between candidate metabolites, 24-hour ambulatory blood pressure, and endothelial function among normotensive individuals, she proposes to collect new metabolomics data from baseline plasma samples donated by 225 participants in an ongoing clinical trial. Overall, the proposed research seeks to improve knowledge of hypertension pathophysiology and provide insight into new approaches for hypertension prevention and treatment. Importantly, this K01 has the potential to meaningfully change public health while addressing the shortage of researchers trained in metabolomics and health in aging.

Public Health Relevance

Identification of metabolites that are predictive of hypertension may provide clues to pathophysiology and additionally suggest therapeutic means to slow, halt, or even reverse course. Given that the majority of older adults have hypertension, and that the proportion of older adults in the United States is projected to double over the next 25 years, this research has the potential to meaningfully impact public health.

National Institute of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
Research Scientist Development Award - Research & Training (K01)
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NHLBI Mentored Clinical and Basic Science Review Committee (MCBS)
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Jaquish, Cashell E
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Brigham and Women's Hospital
United States
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Townsend, Mary K; Aschard, Hugues; De Vivo, Immaculata et al. (2016) Genomics, Telomere Length, Epigenetics, and Metabolomics in the Nurses' Health Studies. Am J Public Health 106:1663-8
Townsend, Mary K; Bao, Ying; Poole, Elizabeth M et al. (2016) Impact of Pre-analytic Blood Sample Collection Factors on Metabolomics. Cancer Epidemiol Biomarkers Prev 25:823-829