Jeremy M. Boss, PhD

Professor, Emory Vaccine Center
Professor and Chair, Department of Microbiology and Immunology, Emory University School of Medicine Professor and Chair, Basic Sciences Research, Emory University School of Medicine

My research centers on the global issue of how immune responses are regulated. I have chosen to approach this problem by focusing on the regulation of gene expression in two systems: the regulation of the human major histocompatibility complex class II genes (MHC class II) and the mechanisms by which tumor necrosis factor (TNF) regulates expression of a wide variety of genes.

The MHC class II genes are a family of genes that encode cell surface glycoproteins that function by presenting processed antigenic peptides to helper T cells. This function is responsible for initiating immune responses to foreign substances and results in the selective control of T cells and the production of specific antibodies. MHC class II products are expressed predominantly on B cells and antigen presenting cells, such as the macrophage. Experiments in the laboratory focus on identifying the role that chromatin plays in controlling gene expression. We use both in vitro and animal model knock-in/out systems to address the regulatory events that occur. One new area of investigation centers on the cell fate differentiation step between B cells and plasma cells. At this step global gene repressors and activators function to reprogram gene expression profiles. Our lab is using the master regulator CIITA as a model gene to study at this interface.

The regulation of genes by TNF marks the initiation of inflammatory responses. TNF controls a wide variety of genes that appear to be regulated by different mechanisms. We have chosen two genes that are regulated by TNF to study, the monocyte chemoattractant protein-1 gene (MCP-1) and the manganous superoxide dismutase gene. For each of these genes, we have identified complex TNF responsive regulatory elements, and for MCP-1 we have found a novel control of chromatin assembly of transcription factors that is mediated by TNF. Experiments are focused on examining this mechanism of control. Additionally, the factors that interact with the MCP-1 regulatory DNA appear to assemble as a multi component complex. Experiments are designed to determine the parameters of this complex both in vitro and in vivo.