Complex metabolic diseases such as cancer, diabetes and obesity result from the interaction of multiple genetic and environmental factors. We are exploring the interaction of epigenetic and genetic variation in the development of complex disease. We utilize an integrative approach combining computational and experimental approaches to study these problems.
We recently have been investigating chromatin modifications in response to high-fat diet in mouse models of obesity (J Biol Chem. 289(34):23557-67 2014) and the potential persistence of these modifications as mediators of long-term disease risk (J Biol Chem. 291(20):10446-55 2016).
Our most recent work examined the variability in chromatin accessibility across different strains of mice with phenotypic diversity in response to a high fat / high-sucrose diet. We demonstrated that specific families of transposable elements are enriched at sites of variable chromatin and that transposable elements of different evolutionary age had unique transcription factor binding sites. Furthermore, CRISPR-Cas9 deletion of variable chromatin sites at evolutionarily younger transposable elements altered the expression of metabolic genes (Epigenetics Chromatin 9:28 2016)
Another area of interest is in the establishment of chromatin domains in development and how disruption of these domains leads to disease progression. We have demonstrated that repressive heterochromatin domains are established at specific genomic loci at certain stages of differentiation (Epigenetics Chromatin 7:23 2014). We have furthermore been investigating how environmental factors disrupt chromatin domains and the potential for these alterations to contribute to disease (P Natl Acad Sci USA.111(40) 2014).
July 18, 2016
September 23, 2014
September 03, 2014
August 26, 2013