Research in the Hamerman Laboratory focuses on the regulation of the innate immune response to pathogens with an emphasis on macrophages and dendritic cells. Macrophages and dendritic cells are distributed throughout the body where they are poised to detect pathogens and to subsequently alert the immune system to the presence of infection through the production of inflammatory mediators. The production of inflammatory mediators, such as tumor necrosis factor (TNF) and other pro-inflammatory cytokines, is tightly regulated. Although these important cytokines are beneficial to the host for pathogen clearance, they can be detrimental if unchecked. This can be seen in both acute settings, such as infection, as well as in the chronic setting of autoimmune diseases.
Macrophages and dendritic cells recognize pathogens by a variety of cell surface and intracellular receptors termed pattern recognition receptors, including the family of Toll-like receptors (TLR). The lab studies how signaling through pattern recognition receptors results in the appropriate inflammatory response by macrophages and dendritic cells. The team is particularly interested in proteins that inhibit signaling through pattern recognition receptors, providing an essential check to the inflammatory response. They study several proteins that inhibit TLR signaling, including BCAP, TREM-2 and DAP12, through biochemical and cellular approaches and in vivo infectious models. The lab focuses on a variety of myeloid cells, including monocytes, macrophages, conventional dendritic cells and plasmacytoid dendritic cells.
The team also has a new interest in the development of cells that participate in innate immune responses, such as macrophages, neutrophils and dendritic cells. This process of myelopoiesis occurs in the bone marrow and can respond dynamically to infection and inflammation to produce more cells when needed, such as during infection. Myeloid progenitors express TLR and can directly respond to these signals to differentiate. The lab is now studying how these myeloid progenitors in the bone marrow increase and modify their output during infection and inflammation, with a focus on TLR and the Type I interferon family of cytokines. Type I interferons are produced during viral infections and certain autoimmune diseases, such as SLE, and the lab is focused on understanding this novel role of these cytokines in driving myelopoiesis.
Hamerman Laboratory studies are focused on understanding how the innate immune response is regulated during infection and inflammation, both at the level of the mature myeloid cells and during their development. These studies will not only shed light onto how the inflammatory response is regulated during infection, but will also give insights in how to manipulate the innate immune system to achieve more efficient elimination of pathogens and to regulate the inflammatory response during disease.