The purpose of this program is to significantly advance our understanding of mechanisms of HDL Dysfunction in Projects (1) familial hypercholesterolemia (2) chronic kidney disease, (3) small RNAs, and (4) reactive dicarbonyl modification to HDL. The proposed research strategies are highly cross-disciplinary and require extensive next-generation RNA sequencing, data analysis, and data integration. An effective and dedicated non- coding RNA and bioinformatics core is essential for the success of the proposed studies in each project and the overall program. Specifically, the Non-Coding RNA and Bioinformatics Core is designed to handle the large volume of sequencing needs and data analyses for all 4 projects. We are highly trained, skilled, and experienced in generating sRNA-seq libraries, bulk total RNA-seq libraries, and 10X Chromium single cell RNA sequencing (scRNA-seq) preparations for high-throughput sequencing. We are proficient in performing quality control steps and completing the sequencing tasks. Furthermore, we have developed in-house sequencing analysis pipelines that will be implemented by computational biologists and biostatisticians under the guidance of an existing informatics team that has worked closely over the past 6 years. The purpose of the Non-Coding RNA and Bioinformatics Core is to use high-throughput RNA sequencing and informatics to analyze small and long RNA expression changes associated with HDL dysfunction and atherosclerosis treatments in a timely and efficiently manner with high-quality data management and integration into complex bioinformatics systems.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Program Projects (P01)
Project #
2P01HL116263-06A1
Application #
10089339
Study Section
Heart, Lung, and Blood Initial Review Group (HLBP)
Program Officer
Liu, Lijuan
Project Start
2014-06-01
Project End
2025-12-31
Budget Start
2020-09-01
Budget End
2021-08-31
Support Year
6
Fiscal Year
2021
Total Cost
Indirect Cost
Name
Vanderbilt University Medical Center
Department
Type
DUNS #
079917897
City
Nashville
State
TN
Country
United States
Zip Code
37232
Allen, Ryan M; Zhao, Shilin; Ramirez Solano, Marisol A et al. (2018) Bioinformatic analysis of endogenous and exogenous small RNAs on lipoproteins. J Extracell Vesicles 7:1506198
Mueller, Paul A; Zhu, Lin; Tavori, Hagai et al. (2018) Deletion of Macrophage Low-Density Lipoprotein Receptor-Related Protein 1 (LRP1) Accelerates Atherosclerosis Regression and Increases C-C Chemokine Receptor Type 7 (CCR7) Expression in Plaque Macrophages. Circulation 138:1850-1863
Li, Kang; Rodosthenous, Rodosthenis S; Kashanchi, Fatah et al. (2018) Advances, challenges, and opportunities in extracellular RNA biology: insights from the NIH exRNA Strategic Workshop. JCI Insight 3:
Babaev, Vladimir R; Ding, Lei; Zhang, Youmin et al. (2018) Loss of 2 Akt (Protein Kinase B) Isoforms in Hematopoietic Cells Diminished Monocyte and Macrophage Survival and Reduces Atherosclerosis in Ldl Receptor-Null Mice. Arterioscler Thromb Vasc Biol :ATVBAHA118312206
Kaseda, R; Tsuchida, Y; Gamboa, J L et al. (2018) Angiotensin receptor blocker vs ACE inhibitor effects on HDL functionality in patients on maintenance hemodialysis. Nutr Metab Cardiovasc Dis 28:582-591
Kaseda, Ryohei; Tsuchida, Yohei; Yang, Hai-Chun et al. (2018) Chronic kidney disease alters lipid trafficking and inflammatory responses in macrophages: effects of liver X receptor agonism. BMC Nephrol 19:17
Babaev, Vladimir R; Huang, Jiansheng; Ding, Lei et al. (2018) Loss of Rictor in Monocyte/Macrophages Suppresses Their Proliferation and Viability Reducing Atherosclerosis in LDLR Null Mice. Front Immunol 9:215
Byram, Kevin W; Oeser, Annette M; Linton, MacRae F et al. (2018) Exercise is Associated With Increased Small HDL Particle Concentration and Decreased Vascular Stiffness in Rheumatoid Arthritis. J Clin Rheumatol 24:417-421
Sedgeman, Leslie R; Beysen, Carine; Allen, Ryan M et al. (2018) Intestinal bile acid sequestration improves glucose control by stimulating hepatic miR-182-5p in type 2 diabetes. Am J Physiol Gastrointest Liver Physiol :
May-Zhang, Linda S; Yermalitsky, Valery; Huang, Jiansheng et al. (2018) Modification by isolevuglandins, highly reactive ?-ketoaldehydes, deleteriously alters high-density lipoprotein structure and function. J Biol Chem 293:9176-9187

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