The purpose of this program is to significantly advance our understanding of mechanisms of HDL Dysfunction in (1) Familial Hypercholesterolemia and (2) Chronic Kidney Disease, as well as the impact of (3) Oxidative modifications to HDL. The proposed research strategies are highly cross disciplinary and require extensive next-generation RNA sequencing and transcriptome-scale analysis. An effective and dedicated non-coding RNA and bioinformatics core is essential for the success of the proposed studies. Specifically, the Non-Coding RNA and Bioinformatics Core is designed to handle the large volume of sequencing needs and data analysis for Projects 1, 2, and 3. We are highly trained, skilled, and published in smRNA-Seq. and RNA seq. Furthermore, we have developed in-house sequencing analysis pipelines that will be implemented by computational biologists and biostatisticians under the guidance of the Core Leader, Dr. Kasey C. Vickers. The purpose of the Non-Coding RNA and Bioinformatics Core is to use massive parallel DNA sequencing to analyze small and long RNA expression and abundance associated with HDL dysfunction in a timely and efficiently manner with high-quality data management and integration into complex bioinformatics systems.

Public Health Relevance

The function of the Non-Coding RNA and Bioinformatics Core is critical to the goals of the proposed projects. Specifically, the Core will be dedicated to accurate sequencing-based profiling of smRNA (mlRNA), long non-coding RNA, and mRNA. Moreover, Core D is designed to seamlessly apply high-level pathway and systems bioinformatics, and biostatistical comparisons and correlation analyses with various HDL functions and parameters.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Program Projects (P01)
Project #
1P01HL116263-01A1
Application #
8693121
Study Section
Heart, Lung, and Blood Initial Review Group (HLBP)
Project Start
Project End
Budget Start
2014-06-01
Budget End
2015-04-30
Support Year
1
Fiscal Year
2014
Total Cost
$263,292
Indirect Cost
$95,411
Name
Vanderbilt University Medical Center
Department
Type
DUNS #
004413456
City
Nashville
State
TN
Country
United States
Zip Code
37212
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Linton, MacRae F; Tao, Huan; Linton, Edward F et al. (2017) SR-BI: A Multifunctional Receptor in Cholesterol Homeostasis and Atherosclerosis. Trends Endocrinol Metab 28:461-472
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Guo, Yan; Strickland, Stephen A; Mohan, Sanjay et al. (2017) MicroRNAs and tRNA-derived fragments predict the transformation of myelodysplastic syndromes to acute myeloid leukemia. Leuk Lymphoma 58:1-15
Babaev, Vladimir R; Ding, Lei; Zhang, Youmin et al. (2016) Macrophage IKK? Deficiency Suppresses Akt Phosphorylation, Reduces Cell Survival, and Decreases Early Atherosclerosis. Arterioscler Thromb Vasc Biol 36:598-607
Michell, Danielle L; Vickers, Kasey C (2016) HDL and microRNA therapeutics in cardiovascular disease. Pharmacol Ther 168:43-52
Ormseth, Michelle J; Yancey, Patricia G; Solus, Joseph F et al. (2016) Effect of Drug Therapy on Net Cholesterol Efflux Capacity of High-Density Lipoprotein-Enriched Serum in Rheumatoid Arthritis. Arthritis Rheumatol 68:2099-105
Ormseth, Michelle J; Stein, C Michael (2016) High-density lipoprotein function in rheumatoid arthritis. Curr Opin Lipidol 27:67-75
Yang, Haichun; Fogo, Agnes B; Kon, Valentina (2016) Kidneys: key modulators of high-density lipoprotein levels and function. Curr Opin Nephrol Hypertens 25:174-9

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