Soloski Lab

Mark J. Soloski, PH.D.
Primary Appointment in Medicine – Division of Rheumatology,
Joint Appointments in Molecular Biology and Genetics, Pathology and Molecular Microbiology and Immunology.

A major focus of the lab is understanding how infection can set the stage for the development of chronic immune-mediated diseases. To investigate this our laboratory has studies the role of cellular immune response in controlling infection with gram-negative bacterial pathogens such as Salmonella typhimurium. This interest is driven not only because these bacteria cause significant acute disease but also due to the etiological link between infection with Salmonella and related species with the development of chronic autoimmune disease. We have recently focused our attention on the role of the intestinal mucosal immune compartment in controlling oral infection. This effort has identified a new unrecognized subset of T cells residing within the epithelial barrier that expands following infection. Current efforts are focused on understanding the recognition properties and effector function of this T cell subset and determining if an analogous population exists in the human mucosa.

A recent new area of interest is to understand the human host immune response to infection with Borrelia burgdorfer, the causative agent of Lyme disease. To date there is little information available as to how various cellular immune elements are mobilized following infection. We hypothesize that the varying pathophysiological outcomes that follow infection with B. burgdorferi are the result of differences in the host immune response to the infection. We are addressing this issue by following a cohort of patients from onset of presentation with symptoms of infection through the course of disease. This effort will attempt to identify cellular and/or molecular biomarkers that associate with effectiveness of bacterial clearance and/or disease pathophysiology and will employ genomic, proteomic and complex immune phenotyping approaches.

My group also has a long standing interest in the study of a novel family of conserved class I histocompatibility proteins termed MHC class Ib molecules. Studies from our laboratory and others have shown that MHC class Ib molecules can function to present peptide epitopes to T cells. Several class Ib molecules have been implicated in the immune response to intracellular bacterial pathogens and mouse/human counterparts have been identified. This information indicates that class Ib molecules have evolved to play key roles in the immune recognition. As part of our overall objective to understand the basic immunobiology of class Ib molecules, we have generated a new murine transgenic model for the analysis of mouse (and human) class Ib function. This model will allow the definition of the role for class Ib molecules in the selection and function of T cells and allow us to examine the range of pathogens for which class Ib molecules play a role in immune recognition. In addition, we study the structure of endogenous self-peptides bound to class Ib molecules. Our goal is to understand physical/chemical basis of peptide binding to class Ib molecules as a means to understand the physiological settings in which these molecules function.