This proposal builds upon the accomplishments made during the previous funding period and requests continuing support of the Center of Biomedical Research Excellence (COBRE) on Obesity and Cardiovascular Diseases (COCVD). Kentucky ranks within the top 10 states for the prevalence of obesity and cardiovascular diseases, and the epidemic is not abating. Thus, it is imperative that mechanisms linking obesity to cardiovascular diseases are identified. During the 4 years of support the COCVD has made significant strides advancing knowledge on obesity-associated cardiovascular diseases through support of junior investigators and the development of research cores. As a result, we have experienced outstanding success, with graduation of 75% of 12 supported junior investigators to independent R01 support, including 15 new NIH R01s. The program has graduated 2 junior faculty/year to NIH R01 level support, with 125 publications from junior investigators, and an additional 318 publications from mentors. In addition, we have supported 7 pilot projects that have contributed to 58 publications. New research cores to quantify obesity phenotypes and to provide analytical services in lipidomics have markedly increased the research infrastructure. As a direct result of COCVD activities, the institution competed successfully for a CTSA to establish the Center for Clinical and Translational Sciences. In the second phase of the COCVD we propose to create a nationally recognized Center of Research Excellence to define mechanisms linking the epidemic of obesity to cardiovascular diseases, the primary cause of death in the obese population. To accomplish this goal, we will (1) develop a critical mass of funded investigators including basic and physician scientists with research programs directly related to the Center's unifying theme, (2) provide strong mentoring programs, (2) recruit new investigators to the Center through pilot project grant support, which will be leveraged by the institution and the CTSA, (4) expand and further develop an Analytical Core (with a focus on lipidomics), a Physiologic Core to quantify obesity and cardiovascular phenotypes, and a Pathology Core to assess tissue histology.

Public Health Relevance

The Center of Biomedical Research Excellence on Obesity and Cardiovascular Diseases seeks to define mechanisms for the rampant prevalence of cardiovascular diseases in the obese population. We will enhance the competitiveness of junior faculty with research programs in this highly significant area through research support, mentoring, and through development and access to cutting-edge research cores.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Exploratory Grants (P20)
Project #
3P20GM103527-10S1
Application #
9552461
Study Section
Special Emphasis Panel (ZGM1)
Program Officer
Liu, Yanping
Project Start
2008-09-08
Project End
2019-07-31
Budget Start
2017-08-01
Budget End
2019-07-31
Support Year
10
Fiscal Year
2017
Total Cost
Indirect Cost
Name
University of Kentucky
Department
Pharmacology
Type
Schools of Medicine
DUNS #
939017877
City
Lexington
State
KY
Country
United States
Zip Code
40526
Jama, Abdulrahman; Huang, Dengtong; Alshudukhi, Abdullah A et al. (2018) Lipin1 is required for skeletal muscle development by regulating MEF2c and MyoD expression. J Physiol :
Federico, Lorenzo; Yang, Liping; Brandon, Jason et al. (2018) Lipid phosphate phosphatase 3 regulates adipocyte sphingolipid synthesis, but not developmental adipogenesis or diet-induced obesity in mice. PLoS One 13:e0198063
Shridas, Preetha; De Beer, Maria C; Webb, Nancy R (2018) High-density lipoprotein inhibits serum amyloid A-mediated reactive oxygen species generation and NLRP3 inflammasome activation. J Biol Chem 293:13257-13269
Wilson, Patricia G; Thompson, Joel C; Shridas, Preetha et al. (2018) Serum Amyloid A Is an Exchangeable Apolipoprotein. Arterioscler Thromb Vasc Biol 38:1890-1900
Petriello, Michael C; Brandon, J Anthony; Hoffman, Jessie et al. (2018) Dioxin-like PCB 126 Increases Systemic Inflammation and Accelerates Atherosclerosis in Lean LDL Receptor-Deficient Mice. Toxicol Sci 162:548-558
Alsiraj, Yasir; Thatcher, Sean E; Blalock, Eric et al. (2018) Sex Chromosome Complement Defines Diffuse Versus Focal Angiotensin II-Induced Aortic Pathology. Arterioscler Thromb Vasc Biol 38:143-153
Thompson, Joel C; Wilson, Patricia G; Wyllie, Alex P et al. (2018) Elevated circulating TGF-? is not the cause of increased atherosclerosis development in biglycan deficient mice. Atherosclerosis 268:68-75
Thalman, Carine; Horta, Guilherme; Qiao, Lianyong et al. (2018) Synaptic phospholipids as a new target for cortical hyperexcitability and E/I balance in psychiatric disorders. Mol Psychiatry 23:1699-1710
Lee, Scott J; Zea, Ryan; Kim, David H et al. (2018) CT texture features of liver parenchyma for predicting development of metastatic disease and overall survival in patients with colorectal cancer. Eur Radiol 28:1520-1528
Brandon, Jason A; Farmer, Brandon C; Williams, Holden C et al. (2018) APOE and Alzheimer's Disease: Neuroimaging of Metabolic and Cerebrovascular Dysfunction. Front Aging Neurosci 10:180

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