Cytokine Imprints;Plasticity in Macrophages;Innate Immune Memory;Autoimmune Diseases;Leukemia;Bioinfomatics;사이토카인;생물정보학;백혈병;면역
We study the immunologic aspects of a very broad range of human diseases, encompassing investigations in the fields of autoimmune diseases, inflammatory diseases, and hematopoiesis such as rheumatoid arthritis, systemic lupus erythematosus, atherosclerosis and leukemia. We are interested in how cytokines and inflammatory factors regulate the activation and function of innate immune and stromal cells, with a focus on macrophages, monocytes and fibroblasts. We are currently studying how cytokines such as IFNs, TNF and IL1 reprogram macrophage responses to the environment by altering transcription factor networks, chromatin states, cell metabolism, and the epigenomic landscape of enhancers. Such reprogramming results in macrophages that are hyper-responsive (primed) or desensitized (tolerized) to inflammatory challenges. To understand of underlying mechanisms, we integrate basic science investigation of signaling and epigenetic mechanisms with translational research using disease models and analysis of human disease samples with genome wide approaches such as single cell RNA-seq, ChIP-seq, and ATAC-seq. We are incorporating a precision medicine approach to identify disease mechanisms and the best therapies for individual patients. Our long-term research goals are to identify signaling and epigenetic mechanisms that can be targeted by new therapies for inflammatory diseases, including biological approaches to enhancing clinical outcomes.