Abstract

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.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project--Cooperative Agreements (U01)
Project #
5U01CA105417-03
Application #
7097308
Study Section
Special Emphasis Panel (ZCA1-SRRB-U (J1))
Program Officer
Marks, Cheryl L
Project Start
2004-08-15
Project End
2009-03-31
Budget Start
2006-07-21
Budget End
2007-03-31
Support Year
3
Fiscal Year
2006
Total Cost
$532,268
Indirect Cost

  Institution

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

  Publications

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
Barrington, William T; Wulfridge, Phillip; Wells, Ann E et al. (2018) Improving Metabolic Health Through Precision Dietetics in Mice. Genetics 208:399-417
Mulligan, Megan K; Mozhui, Khyobeni; Prins, Pjotr et al. (2017) GeneNetwork: A Toolbox for Systems Genetics. Methods Mol Biol 1488:75-120
Kelly, Scott A; Zhao, Liyang; Jung, Kuo-Chen et al. (2017) Prevention of tumorigenesis in mice by exercise is dependent on strain background and timing relative to carcinogen exposure. Sci Rep 7:43086
Donoghue, Lauren J; Livraghi-Butrico, Alessandra; McFadden, Kathryn M et al. (2017) Identification of trans Protein QTL for Secreted Airway Mucins in Mice and a Causal Role for Bpifb1. Genetics 207:801-812
Kelada, Samir N P (2016) Plethysmography Phenotype QTL in Mice Before and After Allergen Sensitization and Challenge. G3 (Bethesda) 6:2857-65
Wang, WeiBo; Wang, Wei; Sun, Wei et al. (2015) Allele-specific copy-number discovery from whole-genome and whole-exome sequencing. Nucleic Acids Res 43:e90
Rutledge, Holly; Baran-Gale, Jeanette; de Villena, Fernando Pardo-Manuel et al. (2015) Identification of microRNAs associated with allergic airway disease using a genetically diverse mouse population. BMC Genomics 16:633
Didion, John P; Morgan, Andrew P; Clayshulte, Amelia M-F et al. (2015) A multi-megabase copy number gain causes maternal transmission ratio distortion on mouse chromosome 2. PLoS Genet 11:e1004850
McLachlan, Sandra M; Aliesky, Holly; Banuelos, Bianca et al. (2014) Immunoglobulin heavy chain variable region and major histocompatibility region genes are linked to induced graves' disease in females from two very large families of recombinant inbred mice. Endocrinology 155:4094-103

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