Complex metabolic diseases such as cancer, diabetes and obesity result from the interaction of multiple genetic and environmental factors. The Schones Lab explores the interaction of epigenetic and genetic variations leading to such complex diseases. We utilize an integrative approach combining computational and experimental approaches to study these problems.
We recently have been investigating chromatin modifications in response to a high-fat diet in mouse models of obesity and the potential persistence of these modifications as mediators of long-term disease risk.
Our most recent work examined the variability in chromatin accessibility across different strains of mice with phenotypic diversity in response to a high-fat or high-sucrose diet. We demonstrated that sites with variable chromatin have enriched specific families of transposable elements and that transposable elements of different evolutionary ages 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.
Another area of interest is establishing chromatin domains in development and how disruption of these domains leads to disease progression. For example, we have demonstrated that repressive heterochromatin domains are established at specific genomic loci at certain stages of differentiation. In addition, we have been investigating how environmental factors disrupt chromatin domains and the potential for these alterations to contribute to disease.
Principal Investigator: Dustin E. Schones, Ph.D.
Dustin E. Schones, Ph.D., is an associate professor in the Department of Diabetes Complications & Metabolism.