School of Public Health
Area of interest
We study the genetic architecture of complex traits, with an emphasis on diseases that are impacted by energy balance, including obesity and cancer. Using polygenic mouse models and high throughput approaches integrating genomics and physiology, our research team identifies genes that control predisposition to complex traits and how these genes interact with each other and with environments such as nutrition and exercise.
In relation to the Lineberger Comprehensive Cancer Center, our research group has focused on an F2 population of mice resulting from a cross between the polygenic obesity model M16i and FVB/NJ-Ten (MMTV-Pym)634Mul, which develop synchronously appearing multifocal tumors involving all of the mammary glands with more than 85% of the animals developing pulmonary metastases. Using SNP genotyping data, we identified 59 modifier loci (quantitative trait loci; QTL) for many cancer and metabolism traits. In addition, we found significant diet (high fat versus low fat) x QTL interactions in 22 cancer modifier genes, including those controlling latency, tumor weight and metastasis. This showed, for the first time, that genes controlling genetic susceptibility to cancer could have greater or lesser effects depending on dietary environment. We have also related genetic susceptibility to cancer with tumor gene expression levels and tumor somatic copy number variation.
More recently, and with newly funded (U01 and RC1) NIH grants, we are focusing on the interactions between physical activity (exercise) and genetic susceptibility to colon cancer using the Collaborative Cross resource. Furthermore, we are studying how host genetic variation controlling variation in gut microbiome levels may relate to host susceptibility to gastric and GI cancers. These new efforts employ the power of the Collaborative Cross (CC), a novel and powerful set of mouse models for complex trait analysis whose use at UNC has been significantly supported by the LCCC. The CC is a very large panel of recombinant inbred (RI) mouse lines derived from a cross of 8 diverse inbred strains, and is the only mammalian resource that has high and uniform genomewide variation effectively randomized across a large, heterogeneous population which also supports integration across environmental and biological conditions and over time. The CC captures the complexity of the mammalian genome and permits modeling of complex systems and interactions that influence disease.
Awards and Honors
2004: Associate Editor, Genetics/Selection/Evolution;
2004: Visiting Scholar, University of Tibet;
2005: Selected to International Review Committee, L’Institut National de la Recherche Agronomique (FR);
2005: Sir John Hammond Lecture, BSAS (UK);
2005: Keynote Lecture, EFAFG, Edinburgh (UK);
2006: USDA Animal Genomics Strategic Plan Task Force;
2007: Editorial Board, Physiological Genomics; 2008: Editorial Board, Mammalian Genome;
2009: Editorial Board, Journal of Biomedicine and Biotechnology;
2009: Chair, Gordon Research Conference on Quantitative Genetics and Genomics;
2010: International Advisory Committee, International Conference on Quantitative Genetics.