Chromatin and Gene Regulation

Chromosomes are compacted into increasingly complex chromatin structures within eukaryotic nuclei. High-throughput sequence-based assays have been developed to identify regions of nucleosome-depleted open chromatin that mark all types of regulatory elements genome-wide in tissues and cell-types. The computational integration of these data with related gene expression, transcription factor binding, and epigenetic data provide a more complete picture of the complex process of gene transcription and regulation. With these data, we are also investigating the effects of genetic variation on regulation, as can been seen through allelic imbalance in signal from chromatin and transcription factor data, as well as in quantitative trait loci (QTL)-based analyses of these data across individuals. Our computational biology lab both applies established analysis tools to data generated in collaboration with other labs as well as develops new analytical techniques to make novel associations.

Inflammatory Bowel Disease

Inflammatory bowel disease (IBD), primarily consisting of Crohn’s disease and ulcerative colitis, is the result of an inappropriate immune response to the intestinal microbiota in a genetically susceptible individual. We have partnered with Dr. Shehzad Sheikh, MD, PhD (Dept of Medicine, CGIBD) to uncover molecular and microbial characteristics of IBD disease phenotypes. We hypothesize that changes in the chromatin landscape in key intestinal cell types such as macrophages, are influenced by the host genetic background and significantly contribute to aberrant intestinal inflammation. Using both human tissue and mouse models, we seek to identify where chromatin is altered, the impacts on gene expression, the contributions of genetic variation, and the relationship to the microbial community in tissues and cells from affected individuals.

Environmental Toxicogenomics

Exposure to naturally occurring toxicants or by-products of manufacturing process can result in serious health challenges. We hypothesize that toxicant exposure can alter normal cellular function through changes in chromatin architecture and transcriptional profiles in tissues or cells contributing to the onset of medical complications. In a collaboration with Dr. Samir Kelada, PhD (Dept of Genetics), we are investigating the effects of exposure to ozone on the lung inflammatory response in the genetically diverse Collaborative Cross mouse model resource. In particular, we are assaying how ozone-induced chromatin structure and gene expression changes in alveolar macrophages, along with genetic variation, explain variability in ozone response.