My research emphasizes the immunologic analysis of macrophages, key cells in the development and execution of immune responses. The induction of macrophage function during an immune response occurs through a multi-step pathway in which responsive cells require interaction with multiple stimuli for the full development of functional activity. To approach this goal, the lab has produced a panel of molecular probes that recognize genes which are expressed by macrophages activated by IFN-gamma to express microbial and tumor cell killing. These studies have provided the first identification of molecular genetic changes occurring in activated macrophages committed to a specific effector cell function.
Current work is focused in several areas.
First, the nature of the gene products identified by these probes is being characterized, as a first step to understanding the role of these products in the development and function of activated macrophages. The pathway of signal transduction from the IFN-gamma receptor in macrophages also is being analyzed to determine how such transcriptional control is initiated in macrophages. Finally, in an experimental and clinical application of the work, the molecular probes are being used to characterize the activation profile of macrophages recruited to tumor and inflammatory sites in vivo. It is hoped the work ultimately will reveal target genes of importance that may be modified to control the macrophage component of the host response to infectious diseases and cancer. Promoter analysis of an interferon-inducible gene associated with macrophage activation.