Work in my laboratory focuses on the adaptive immune system, a unique feature of vertebrates where the sensors of the body responsible for preventing diseases recognize the specific molecular patterns of diseases that allow discrimination between healthy tissues and those that would harm the body. We focus on the MHC class I antigen presentation pathway, the process by which cells alert the adaptive immune system to the presence of intracellular pathogens. Antigen presentation relies on the degradation of foreign proteins into short peptide sequence which can then bind to the MHC class I molecule. Once bound, the peptide-MHC class I complex is displayed on the cell surface for surveillance by cytotoxic CD8+ T cells that are looking for evidence of specific diseases. We are attempting to answer questions related to the precursor antigenic protein’s synthesis and degradation. Evidence is accumulating that many of these precursor proteins are degraded quite rapidly following their synthesis and we are attempting to pin down the cellular mechanisms that control such rapid protein turnover and how it relates to antigen presentation. Many of our studies focus on the role of the protein ubiquitin and other ubiquitin-like proteins that are involved in a range of cellular functions. We are studying many different aspects of ubiquitin modification to identify the enzymes that dictate how successful antigen presentation occurs. Our long term goals are to modulate antigen presentation with a variety of chemical inhibitors of the ubiquitin pathway.
We extend our studies of the adaptive immune system from the individual cell to the larger ecosystem in the attempt to answer questions about the true role of adaptive immunity in our evolution. Our goal is to develop a variety of assays that can be used by researchers in the field to determine the relative immune status of animals as it relates to their environment and each other. From salmon to deer mice, we are collaborating with numerous research groups to quantify different measures of adaptive immunity to understand how the environment can shape immunity and in turn how the immune system drives evolution of both vertebrates and the microbial pathogens that prey upon them.
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