Researchers

It has been well established that a major component of the host leukocytic infiltrate associated with malignant tumors is macrophages. Macrophages have a wide range of essential functions for the host immune system that include phagocytosis, secretion of cytokines, growth factors, lysozymes, complement components, coagulation factors, prostaglandins and proteases. However, the role of tumor-associated macrophages (TAMs) in the progression of malignant tumors is ambiguous. Research has suggested that TAMs can have tumorigenic or tumoricidal effects, the determining factor being the level and type of cytokines secreted by TAMs. The mechanism by which TAMs are activated will determine what cytokine response is elicited, and therefore dictate their role in tumor progression. However, the signal transduction cascades in TAMs that lead to cytokine production have not been defined. Prof. Schorey's lab is characterizing the role of the mitogen activated protein kinases (MAPKs) in macrophage activation. The MAPKs are a family of kinases necessary for the inflammatory response of macrophages and are therefore a potential means by which TAMs regulate their cytokine response. His research is focused on defining the activation state of the MAPK signal transduction cascade in infiltrating TAMs using a B16 murine melanoma model. His group is using various techniques to characterize the MAPK activity and the cytokine profile within the tumors including RT-PCR, ELISAs and Western blots. His long-term goal is to define methods which can modify the macrophage signaling response and promote the activation of the macrophage's anti-tumor response.

Prof. Schorey is also interested in macrophage activation in combination with infectious organisms such as mycobacterium. Mycobacteria are intra-macrophage pathogens and have evolved mechanisms to both avoid the hash lysosomal environment within the macrophage and to obtain the necessary nutrients for its survival and replication. His lab is interested in the mechanisms of mycobacterial invasion and macrophage signaling responses upon infection and how these responses result in either mycobacterial survival or macrophage control of the infection.