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.<\/p>\n
Inflammatory bowel disease (IBD), primarily consisting of Crohn\u2019s 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 (Dept of Medicine, CGIBD) and Dr. Praveen Sethupathy (Cornell Univ) to uncover molecular determinants of IBD disease phenotypes. In particular, we hypothesize that changes in gene expression profiles mediated by an altered chromatin landscape in key intestinal cell types such as macrophages, in part influenced by the host genetic background, are significantly contributing to aberrant intestinal inflammation. Using both human tissue and mouse models, we seek to identify where chromatin is altered, the impacts on gene expression, and how these are driven by genetic variation in affected individuals.<\/p>\n
Exposure to naturally occurring inhalational toxicants can result in serious health challenges. In particular, exposure to high levels of ozone can trigger or exacerbate serious medical conditions such as asthma and COPD. We hypothesize that ozone exposure can alter normal cellular function through changes to the chromatin architecture and transcriptional profiles in tissues contributing to the onset of health complications. In collaboration with Dr. Samir Kelada (Dept of Genetics), we are investigating the molecular effects of ozone exposure in lungs of genetically diverse mice within the Collaborative Cross mouse resource. Better understanding these effects in mice will provide clues as to how ozone is affecting humans.<\/p>\n