Research Projects

All the different types of cells in the hematopoietic system contain identical copies of the genome and yet fulfill distinct roles in immunity. These unique cell identities emerges from differential expression of the genes in the underlying regulatory networks. Cis-regulatory elements -- including promoters, enhancers, insulators, etc -- are critical for the fine-tuning of transcription factors that activate or repress genes. Analysis of chromatin state can reveal the genomic location, activity, and binding of these regulatory regions (see "Background on Gene Regulation" below). By reconstructing the regulatory networks, we can better understand the balance of 'nature' (how its identity is programmed through development) and nurture (how it responds to its environment) in defining a cell's role in the immune system. With recent advances in experimental technology and computational analysis of the resulting 'big data', we aim to apply chromatin analysis to answering immunological questions on environmental response, immune interactions, and hematopoiesis. The results will prove vital to the next generation of medicine that targets the specific fault in gene regulation that is responsible for the disease in order to achieve an effective and precise treatment. Using rheumatic disease -- such as rheumatoid arthritis, systemic sclerosis/scleroderma, and lupus -- as a model, we are mapping the gene regulatory networks of macrophages in order to understand their role and function. This work will provide a better understanding of how macrophages are perturbed in these autoimmune diseases and may offer more effective targets for treatment.