Chromatin and Gene Regulation

Chromosomes are compacted into increasingly complex chromatin structures within eukaryotic nuclei. High-throughput sequence-based assays, such as ATAC-seq, 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 complementary 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 quantitative trait loci (QTL)-based analyses of these data across individuals.

Inflammatory Bowel Diseases

Inflammatory bowel disease (IBD), primarily consisting of Crohn’s disease and ulcerative colitis, results from an inappropriate immune response to the intestinal microbiota in a genetically susceptible individual. IBD is highly heterogeneous with variation in presentation, progression, and response to treatment across pediatric and adult patients. There is no cure and current treatments simply aim to manage the disease. We have a long-term collaboration with Dr. Shehzad Sheikh (Dept of Medicine, CGIBD) focused on uncovering molecular contributors to IBD disease phenotypes. We hypothesize that changes in the transcriptional and chromatin landscape in relevant tissues and cells, influenced by the host genetic background, can significantly increase risk for developing IBD. Spearheaded by the Sheikh lab, we have generated gene expression and chromatin accessibility data in >200 colonic tissue samples from genotyped and well-phenotyped IBD patients and non-IBD controls. We are using these data to investigate molecular changes in IBD patients and their association with disease.

Computational Genomics Analysis Methods

Accurate and useful interpretation of genomic data requires rigorous and creative analytical methods. This can span from the development of a completely novel method and accompanying software to new and creative uses of existing techniques. We employ both strategies, driven by our goal to address knowledge gaps in our understanding of the genetics and genomics of complex traits.