Ph.D., Professor and Chair, Department of Microbiology and Immunology.
Dr. Boss’s lab focuses on the regulation of gene expression in the immune system. Several projects are currently being pursued. Two of these projects focus on the mechanisms of regulation and consequence of expression of the major histocompatibility complex class II genes. These genes are regulated at the transcriptional level by a complex series of transcription factors, coactivators and chromatin modifiers. The current goals are to understand the regulatory and functional mechanisms that control the expression and activity of the coactivator CIITA, which is the master regulator of this system and antigen processing. We recently found that transcriptional insulator regions and the factor CTCF regulates MHC-II genes by reorganizing the chromatin architecture of the MHC class II locus. Experiments to map this novel organization and understand the role that reorganization of the chromatin plays are being performed. Molecular, biochemical and novel animal models are being used to study the above. The genetic and biochemical studies are ultimately dedicated to discovering novel approaches to manipulate the activity of these factors through cytokines or drugs that would increase transplantation success, improve immune responses to infectious agents, or improve the design of immune based therapies to autoimmune disorders.
The laboratory has two new projects. One of these involves a collaboration with Dr. Rafi Ahmed and seeks to understand the regulation of the Programmed Death-1 gene (PD-1). PD-1 is expressed on antigen specific T cells following a chronic exposure to antigen such as that experienced during a chronic viral infection (HIV, HCV, etc). PD-1 mediated signaling results in a phenotype of T cell exhaustion in which the antigenic T cell can no longer proliferate and make cytokines in response to antigenic stimulation. Molecular blockade of the PD-1 signal, results in a reinvigoration of the T cell and activation of the cell’s effector function. We have begun to characterize the regulation of this system and have experiments designed to understand how the regulation of this gene affects the ability of HIV-specific T cells to fight the infection. This system is regulated ina complex manner that involves activating and repression pathways, as well as dynamic epigenetic mechanisms.