My career goal is to become an independent investigator focused on applying laboratory-based techniques assessing HDL functions to large human populations. I have focused thus far on acquiring clinical research skills allowing me to pursue broad epidemiologic assessments of novel biomarkers in improving coronary disease risk prediction in the Dallas Heart Study, culminating in several first-author publications and completion of a Master's Degree in Clinical Sciences. I am now positioned to apply this expertise to the biomarker area that I am most interested in-HDL function. My immediate research goals are based on evidence that directly assessing HDL functions in human studies may lead to better targeting of HDL-modifying therapies aimed at reducing cardiovascular disease (CVD) risk. These focused career goals mandate a mentored career development pathway to acquire the necessary laboratory-based skill sets to gain independence as a translational clinician investigator in the specific field of HDL metabolism and CVD. Key elements of my career development plan include: 1) multi-disciplinary mentorship: Dr. Philip Shaul as primary mentor, an established translational scientist, and Dr. James de Lemos as co-mentor, my current mentor in population science research and director of the Dallas Heart Study biomarker core;2) coursework in laboratory and clinical research;3) direct laboratory training in HDL function studies (Philip Shaul, UTSW;Dan Rader, Penn);and preparation for R01 grant application. The objective of this proposal is to systematically investigate two major HDL functions in relation to CHD in the general population. My central hypothesis is that plasma measurements of HDL-mediated macrophage-specific cholesterol efflux and HDL activation of eNOS (HDL functions) will vary significantly according to race, sex, and metabolic status and inversely correlate with vascular disease independent of HDL-C. I plan to test this hypothesis by prospectively measuring HDL function in an extensively phenotyped existing biobank of human plasma collected from the Dallas Heart Study (n=2,971;50% African American;50% women) to pursue the following three specific aims: 1) identify the biological factors influencing variation n HDL functions across a diverse population;2) determine the associations of paraoxonase-1 (PON-1) activity and genotype with HDL functions;3) comprehensively investigate the role of HDL functions in predicting CHD. These studies are anticipated to have an important positive impact, because the comprehensive assessment of the cardiovascular epidemiology of HDL function will rapidly facilitate clinical investigations targeting functional HDL pathways rather than simple concentration of HDL-C to reduce CHD risk. UT Southwestern combines extraordinary epidemiologic and translational research opportunities and faculty development programs that will ensure the PI's successful clinical research career, specifically the Dallas Heart Study led by Dr. Helen Hobbs, the Center for Nutrition led by Dr. Scott Grundy, and the Department of Clinical Sciences led by Dr. Milton Packer.

National Institute of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
Clinical Investigator Award (CIA) (K08)
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Special Emphasis Panel (ZHL1-CSR-K (F2))
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Wright, Jacqueline
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University of Texas Sw Medical Center Dallas
Internal Medicine/Medicine
Schools of Medicine
United States
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Singh, Kavisha; Rohatgi, Anand (2018) Examining the paradox of high high-density lipoprotein and elevated cardiovascular risk. J Thorac Dis 10:109-112
Sarzynski, Mark A; Ruiz-Ramie, Jonathan J; Barber, Jacob L et al. (2018) Effects of Increasing Exercise Intensity and Dose on Multiple Measures of HDL (High-Density Lipoprotein) Function. Arterioscler Thromb Vasc Biol 38:943-952
Rao, Prahlad K; Merath, Kate; Drigalenko, Eugene et al. (2018) Proteomic characterization of high-density lipoprotein particles in patients with non-alcoholic fatty liver disease. Clin Proteomics 15:10
Chindhy, Shahzad; Joshi, Parag; Khera, Amit et al. (2018) Impaired Renal Function on Cholesterol Efflux Capacity, HDL Particle Number, and Cardiovascular Events. J Am Coll Cardiol 72:698-700
Mani, Preethi; Ren, Hao-Yu; Neeland, Ian J et al. (2017) The association between HDL particle concentration and incident metabolic syndrome in the multi-ethnic Dallas Heart Study. Diabetes Metab Syndr 11 Suppl 1:S175-S179
Lew, Jeanney; Sanghavi, Monika; Ayers, Colby R et al. (2017) Sex-Based Differences in Cardiometabolic Biomarkers. Circulation 135:544-555
Ren, Hao-Yu; Khera, Amit; de Lemos, James A et al. (2017) Soluble endothelial cell-selective adhesion molecule and incident cardiovascular events in a multiethnic population. Am Heart J 191:55-61
Khine, Htet W; Teiber, John F; Haley, Robert W et al. (2017) Association of the serum myeloperoxidase/high-density lipoprotein particle ratio and incident cardiovascular events in a multi-ethnic population: Observations from the Dallas Heart Study. Atherosclerosis 263:156-162
Brownell, Nicholas K; Khera, Amit; de Lemos, James A et al. (2016) Association Between Peptidoglycan Recognition Protein-1 and Incident Atherosclerotic Cardiovascular Disease Events: The Dallas Heart Study. J Am Coll Cardiol 67:2310-2312
Brownell, Nicholas; Rohatgi, Anand (2016) Modulating cholesterol efflux capacity to improve cardiovascular disease. Curr Opin Lipidol 27:398-407

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