The proposed studies will build upon our recent research into genetic networks. We will be extending these, with an initial emphasis on colon and breast cancer, to include serum, urine, and other physiological analyses to develop models of a 'cancer susceptibility state' in order build better mouse models to investigate cancer predisposition and the mechanism by which an individuals genetic makeup and environmental exposure influences susceptibility and eventual response to therapy. Our definition of the cancer susceptibility state will draw from high-throughput methods for defining RNA and protein expression and high-throughput methods for defining genes that control that expression. We will also be addressing several critical issues in cancer research including how diet influence genetic networks associated with cancer susceptibility, the role of obesity in contributing to cancer susceptibility, how environmental exposures differ from genetic induction, among others. This research is definitely a new paradigm for cancer research and should lead to new biomarkers for susceptibility, a better understanding of intermediate phenotypes contributing to cancer susceptibility, and the role of biological plasticity and network switching in cancer predisposition with direct applications to human biology.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project--Cooperative Agreements (U01)
Project #
5U01CA105417-05
Application #
7408034
Study Section
Special Emphasis Panel (ZCA1-SRRB-U (J1))
Program Officer
Marks, Cheryl L
Project Start
2004-08-15
Project End
2009-08-31
Budget Start
2008-05-13
Budget End
2009-08-31
Support Year
5
Fiscal Year
2008
Total Cost
$594,692
Indirect Cost
Name
University of North Carolina Chapel Hill
Department
Genetics
Type
Schools of Medicine
DUNS #
608195277
City
Chapel Hill
State
NC
Country
United States
Zip Code
27599
Wells, Ann; Barrington, William T; Dearth, Stephen et al. (2018) Tissue Level Diet and Sex-by-Diet Interactions Reveal Unique Metabolite and Clustering Profiles Using Untargeted Liquid Chromatography-Mass Spectrometry on Adipose, Skeletal Muscle, and Liver Tissue in C57BL6/J Mice. J Proteome Res 17:1077-1090
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