The immune system leverages immense molecular diversity in the T, B, and NK cell receptor repertoires to distinguish between normal cells and cells altered by infection or cancer. This molecular diversity often makes understanding exactly what is recognized during the course of an immune response extremely challenging. As a result, efforts to study antigen recognition have often been limited to working with model antigens.
Our group focuses on understanding and manipulating ‘natural’ adaptive immune responses in the context of cancer and infection. We use a variety of strategies and techniques including protein biochemistry, protein engineering, sequencing, and bioinformatics to 1) identify immune cells of interest, 2) determine the sequences of their antigen receptors, 3) directly determine what the immune response is ‘seeing’ in response to cancer or infection, and 4) answer questions about how the immune system composition and dynamics affect the success or failure of an immune response. This type of systematic, unbiased examination of the antigen recognition repertoire of any given T or NK cell receptor has, until recently, been extremely difficult. With this information, we will be able to rationally engineer new methods to more specifically and potently mount a potent immune response.
We are also interested in adapting what we learn about immune recognition to better understand other systems that rely upon diverse molecular recognition, as well as to engineer novel diverse protein repertoire systems.
The immune system’s ability to detect and eliminate cancerous cells has long been of potential interest as a therapeutic avenue. In recent years, advances such as antigen-specific vaccines and T cell checkpoint inhibition have transformed how we treat cancers. In spite of this, these treatments are not universally successful: there is huge variability in effectiveness […]
Engineered T cells, primarily expressing chimeric antigen receptors (CARs), have shown tremendous promise as cancer treatments. However, CAR treatment has shown efficacy in only some types of cancer, and can have serious side effects. We are working to apply our expertise in immune recognition and signaling to engineer safer and more broadly effective CARs.
Human NK Cells utilize a repertoire of peptide-MHC-recognizing activating and inhibitory receptors, called KIRs, that govern their function. KIR recognition and activation are key for NK cell function, and certain KIR alleles have shown association with resistance or susceptibility to disease. While it is known that some degree of peptide specificity is inherent in KIR […]
In addition to their roles in the immune system, peptide-MHCs and their receptors have been shown to profoundly affect neural connectivity and function. However, what role the presented peptides play in this function, and whether different MHC alleles differentially affect activity, are unknown. We are studying these interactions to create tools that will allow us […]