Five years of funding are requested to further develop a Center of Biomedical Research Excellence at Kansas University Medical Center with a focus on Nuclear Receptors and their Role in Liver Health and Disease. Five talented new faculty who share this research interest were selected with the goal of helping them become funded, independent investigators. A PI, co-PI, an internal advisory committee of experienced senior faculty and an external advisory committee of prominent scientists have been assembled to mentor them to this goal. The Center will also help provide infrastructure and equipment to supplement the research environment. Ultimately, through the achievement of these initial goals, the final long-range goal is the submission of a program project grant application. An important feature of this Proposal is that for each initial junior faculty member, two co-mentors have been assigned and individual mentoring plans and timetables have been developed. Central features of the mentoring plans include ongoing critical evaluation of the research project by the mentors and lAC, semiannual conferences with EAC members, and special training on statistics, manuscript and grant writing, and teaching. The first 6 junior faculty assigned to this COBRE have competed successfully for independent NIH ROI-type research support. The same is expected of the present junior faculty. Once the present junior faculty is funded externally, they will financially rotate off the grant to make room for addition of new junior faculty members. Another important feature of the Proposal is to maintain 4 research Cores to provide additional research support for the Center's faculty. These cores include an administrative Core as well as Cores in the areas of biospecimen, histopathology, analytical, and sequencing. In summary, the outstanding combination of scientific talent, existing research environment, and new core facilities ensure that this proposed Center will further foster the development of a thematic multidisciplinary research center, to enhance the ability of new investigators to compete independently for complementary NIH and other external peer-reviewed support, and to strengthen existing biomedical research infrastructure at KUMC.

Public Health Relevance

The liver has many functions in the body, such as elimination of drugs and other non-nutritious chemicals in our diet;interconverting fat, glucose, and amino acids;regulating the amount of cholesterol, sugar, and clotting agents;secreting bile acids for the absorption of lipids and lipid-soluble vitamins from our diets, etc. This interdisciplinary group of scientists are working together to understand how the liver performs these functions and how to repair the liver when it fails.

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
Exploratory Grants (P20)
Project #
2P20RR021940-06
Application #
8150136
Study Section
Special Emphasis Panel (ZRR1-RI-B (01))
Program Officer
Caldwell, Sheila
Project Start
2006-06-01
Project End
2016-06-30
Budget Start
2011-09-02
Budget End
2012-06-30
Support Year
6
Fiscal Year
2011
Total Cost
$2,160,121
Indirect Cost
Name
University of Kansas
Department
Pharmacology
Type
Schools of Medicine
DUNS #
016060860
City
Kansas City
State
KS
Country
United States
Zip Code
66160
Weemhoff, James L; Woolbright, Benjamin L; Jenkins, Rosalind E et al. (2017) Plasma biomarkers to study mechanisms of liver injury in patients with hypoxic hepatitis. Liver Int 37:377-384
McCracken, Jennifer M; Chalise, Prabhakar; Briley, Shawn M et al. (2017) C57BL/6 Substrains Exhibit Different Responses to Acute Carbon Tetrachloride Exposure: Implications for Work Involving Transgenic Mice. Gene Expr 17:187-205
Li, Jibiao; Wang, Yifeng; Matye, David J et al. (2017) Sortilin 1 Modulates Hepatic Cholesterol Lipotoxicity in Mice via Functional Interaction with Liver Carboxylesterase 1. J Biol Chem 292:146-160
Jiang, Lu; Sun, Lina; Edwards, Genea et al. (2017) Increased YAP Activation Is Associated With Hepatic Cyst Epithelial Cell Proliferation in ARPKD/CHF. Gene Expr 17:313-326
Woolbright, Benjamin L; Williams, C David; Ni, Hongmin et al. (2017) Microcystin-LR induced liver injury in mice and in primary human hepatocytes is caused by oncotic necrosis. Toxicon 125:99-109
Chavan, Hemantkumar; Christudoss, Pamela; Mickey, Kristen et al. (2017) Arsenite Effects on Mitochondrial Bioenergetics in Human and Mouse Primary Hepatocytes Follow a Nonlinear Dose Response. Oxid Med Cell Longev 2017:9251303
Tikhanovich, Irina; Zhao, Jie; Olson, Jody et al. (2017) Protein arginine methyltransferase 1 modulates innate immune responses through regulation of peroxisome proliferator-activated receptor ?-dependent macrophage differentiation. J Biol Chem 292:6882-6894
Kandel, Sylvie E; Han, Lyrialle W; Mao, Qingcheng et al. (2017) Digging Deeper into CYP3A Testosterone Metabolism: Kinetic, Regioselectivity, and Stereoselectivity Differences between CYP3A4/5 and CYP3A7. Drug Metab Dispos 45:1266-1275
Li, Jibiao; Chen, Cheng; Li, Yuan et al. (2017) Inhibition of insulin/PI3K/AKT signaling decreases adipose Sortilin 1 in mice and 3T3-L1 adipocytes. Biochim Biophys Acta 1863:2924-2933
Zhao, Jie; Adams, Abby; Roberts, Ben et al. (2017) PRMT1 and JMJD6 dependent arginine methylation regulate HNF4? expression and hepatocyte proliferation. Hepatology :

Showing the most recent 10 out of 354 publications