This K01 Career Development Award application proposes a multidisciplinary 4-year training program to provide the candidate, Dr. Qibin Qi, with the experience and resources necessary to launch a successful career as an independent investigator. The training plan, developed closely with primary mentor Dr. Kaplan Robert, co-mentor Dr. Kathryn Anastos, and an Advisory Committee, will broaden Dr. Qi's research experience and expertise, including metabolomics, biostatistics and HIV infection and cardiovascular disease (CVD) epidemiology. The proposed research project, building upon two well-characterized HIV cohorts (the Women's Interagency HIV Study [WIHS] and the Multicenter AIDS Cohort Study [MACS]), offers the candidate an outstanding opportunity to become proficient in the novel area of metabolomics research as well as in HIV infection and CVD epidemiology. Taking advantage of archived blood samples, extensive data on HIV-infection related factors, longitudinal measurements of carotid artery plaque, and genomic data in the WIHS and MACS, this project proposes to examine plasma levels of metabolites among 495 women and men, aged = 45 years old, without carotid artery plaque at baseline (338 HIV+ and 157 HIV- subjects; 103 subjects had incident carotid plaque over 7-year follow-up measured by B mode ultrasound). Associations of HIV infection and related factors with prior informed cardiometabolic-associated metabolites (e.g., branched-chain amino acids), and associations between these metabolites and progression of subclinical carotid atherosclerosis (incident carotid artery plaque) will be examined. In exploratory analyses, advance analytical approached (e.g., network analysis) will be applied to identify novel metabolomic signatures related to HIV infection and subclinical atherosclerosis progression, and to generate a network illustrating interrelationships between genes, metabolites, HIV infection and CVD. In addition, potential HIV-specific metabolomic findings will be examined through collaborations with HIV-uninfected population studies. Findings from this study will provide preliminary data for a larger study proposal to measure metabolomics profiling more comprehensively and longitudinally. These studies will advance our understanding of pathogenesis of HIV infection and CVD and provide useful information for effective strategies in the prevention and management of CVD in HIV-infected patients.

Public Health Relevance

With long-term survival of HIV-infected patients (even reaching normal life expectancy) on highly active antiretroviral therapy, CVD has become a leading source of morbidity and mortality. The proposed research project will identify potential biomarkers and targets for individual risk prediction and prevention and holds promise for personalizing antiretroviral therapy medication choice and other interventions to avert CVD among HIV-infected patients.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Scientist Development Award - Research & Training (K01)
Project #
5K01HL129892-03
Application #
9120269
Study Section
NHLBI Mentored Clinical and Basic Science Review Committee (MCBS)
Program Officer
Reis, Jared P
Project Start
2015-08-15
Project End
2019-05-31
Budget Start
2016-06-01
Budget End
2017-05-31
Support Year
3
Fiscal Year
2016
Total Cost
Indirect Cost
Name
Albert Einstein College of Medicine, Inc
Department
Type
DUNS #
079783367
City
Bronx
State
NY
Country
United States
Zip Code
10461
Strizich, Garrett; Kaplan, Robert C; Sotres-Alvarez, Daniela et al. (2018) Objectively Measured Sedentary Behavior, Physical Activity, and Cardiometabolic Risk in Hispanic Youth: Hispanic Community Health Study/Study of Latino Youth. J Clin Endocrinol Metab 103:3289-3298
Wang, Zheng; Zolnik, Christine P; Qiu, Yunping et al. (2018) Comparison of Fecal Collection Methods for Microbiome and Metabolomics Studies. Front Cell Infect Microbiol 8:301
Moon, Jee-Young; Zolnik, Christine P; Wang, Zheng et al. (2018) Gut microbiota and plasma metabolites associated with diabetes in women with, or at high risk for, HIV infection. EBioMedicine 37:392-400
Shan, Zhilei; Clish, Clary B; Hua, Simin et al. (2018) Gut Microbial-Related Choline Metabolite Trimethylamine-N-Oxide Is Associated With Progression of Carotid Artery Atherosclerosis in HIV Infection. J Infect Dis 218:1474-1479
Qi, Qibin; Hua, Simin; Clish, Clary B et al. (2018) Plasma Tryptophan-Kynurenine Metabolites Are Altered in Human Immunodeficiency Virus Infection and Associated With Progression of Carotid Artery Atherosclerosis. Clin Infect Dis 67:235-242
Guo, Y; Moon, J-Y; Laurie, C C et al. (2018) Genetic predisposition to obesity is associated with asthma in US Hispanics/Latinos: Results from the Hispanic Community Health Study/Study of Latinos. Allergy 73:1547-1550
Wassertheil-Smoller, Sylvia; Qi, Qibin; Dave, Tushar et al. (2018) Polygenic Risk for Depression Increases Risk of Ischemic Stroke: From the Stroke Genetics Network Study. Stroke 49:543-548
Fernández-Rhodes, Lindsay; Robinson, Whitney R; Sotres-Alvarez, Daniela et al. (2017) Accuracy of Self-reported Weight in Hispanic/Latino Adults of the Hispanic Community Health Study/Study of Latinos. Epidemiology 28:847-853
Raffield, Laura M; Louie, Tin; Sofer, Tamar et al. (2017) Genome-wide association study of iron traits and relation to diabetes in the Hispanic Community Health Study/Study of Latinos (HCHS/SOL): potential genomic intersection of iron and glucose regulation? Hum Mol Genet 26:1966-1978
Wang, Xueyin; Strizich, Garrett; Hua, Simin et al. (2017) Objectively Measured Sedentary Time and Cardiovascular Risk Factor Control in US Hispanics/Latinos With Diabetes Mellitus: Results From the Hispanic Community Health Study/Study of Latinos (HCHS/SOL). J Am Heart Assoc 6:

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