Profiles

The Hoffmann laboratory focuses on the signaling systems that control innate and adaptive immunity. A central theme is that signaling network dynamics determine biological specificity. We have contributed to an understanding of how NFκB and IRF signaling dynamics are regulated, how these are altered during cell differentiation and in human disease contexts, and how rational drug targeting strategies may be applied to correct misregulation. A wide range of experimental work in animals and cell culture, at single-molecule to genome-wide scales, is coordinated with computational modeling. The laboratory currently has three biological foci: 1) macrophages: how their functions are regulated in a stimulus-specific and context-dependent manner, and how prior history of exposure may be harnessed for innate immune training; 2) B-cells: how the intra-cellular molecular regulatory networks control fate decisions of cell death and cell division, and how inter-cellular networks in the germinal center generate the antibody repertoire in response to vaccination; 3) hematopoiesis: how signaling pathways inside and between cells regulate population dynamics via cell fate decisions of cell division, cell death, and differentiation.