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 #
5P20GM103527-07
Application #
8733718
Study Section
Special Emphasis Panel (ZGM1-TWD-Y (C2))
Program Officer
Liu, Yanping
Project Start
2008-09-08
Project End
2018-07-31
Budget Start
2014-08-01
Budget End
2015-07-31
Support Year
7
Fiscal Year
2014
Total Cost
$2,250,588
Indirect Cost
$750,589
Name
University of Kentucky
Department
Pharmacology
Type
Schools of Medicine
DUNS #
939017877
City
Lexington
State
KY
Country
United States
Zip Code
40506
Song, Eun Suk; Jang, HyeIn; Guo, Hou-Fu et al. (2017) Inositol phosphates and phosphoinositides activate insulin-degrading enzyme, while phosphoinositides also mediate binding to endosomes. Proc Natl Acad Sci U S A 114:E2826-E2835
Bradford, Emily M; Ryu, Stacy H; Singh, Ajay Pal et al. (2017) Epithelial TNF Receptor Signaling Promotes Mucosal Repair in Inflammatory Bowel Disease. J Immunol 199:1886-1897
Pumphrey, Ashley L; Ye, Shaojing; Yang, Zhengshi et al. (2017) Cardiac Chemical Exchange Saturation Transfer MR Imaging Tracking of Cell Survival or Rejection in Mouse Models of Cell Therapy. Radiology 282:131-138
Muniappan, Latha; Javidan, Aida; Jiang, Weihua et al. (2017) Calpain Inhibition Attenuates Adipose Tissue Inflammation and Fibrosis in Diet-induced Obese Mice. Sci Rep 7:14398
Adamiak, M; Abdelbaset-Ismail, A; Suszynska, M et al. (2017) Novel evidence that the mannan-binding lectin pathway of complement activation plays a pivotal role in triggering mobilization of hematopoietic stem/progenitor cells by activation of both the complement and coagulation cascades. Leukemia 31:262-265
Adamiak, Mateusz; Chelvarajan, Lakshman; Lynch, Kevin R et al. (2017) Mobilization studies in mice deficient in sphingosine kinase 2 support a crucial role of the plasma level of sphingosine-1-phosphate in the egress of hematopoietic stem progenitor cells. Oncotarget 8:65588-65600
Wysoczynski, Marcin; Adamiak, Mateusz; Suszynska, Malwina et al. (2017) Poor Mobilization in T-Cell-Deficient Nude Mice Is Explained by Defective Activation of Granulocytes and Monocytes. Cell Transplant 26:83-93
Brown, J Mark; Temel, Ryan E; Graf, Gregory A (2017) Para-bile-osis Establishes a Role for Nonbiliary Macrophage to Feces Reverse Cholesterol Transport. Arterioscler Thromb Vasc Biol 37:738-739
Akenhead, Michael L; Fukuda, Shunichi; Schmid-Schönbein, Geert W et al. (2017) Fluid shear-induced cathepsin B release in the control of Mac1-dependent neutrophil adhesion. J Leukoc Biol 102:117-126
Wang, Yu; Shoemaker, Robin; Powell, David et al. (2017) Differential effects of Mas receptor deficiency on cardiac function and blood pressure in obese male and female mice. Am J Physiol Heart Circ Physiol 312:H459-H468

Showing the most recent 10 out of 197 publications