Our Research In A Nutshell

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.

Engineering Chimeric Antigen Receptors for Better Recognition and Function

Engineered T cell therapies, including CAR-T cells, have shown tremendous promise as cancer treatments. However, they have so far shown efficacy for only some types of cancer.  We design and use high throughput screening approaches to understand the signaling pathways and cell phenotypes that make T cell therapies effective. We use this information to aid […]

New Methods for Studying and Designing pMHC-TCR Interactions

T cell mediated immunity involves immense molecular diversity on the pMHC and TCR sides. Mapping TCRs to the pMHCs they recognize will aid in understanding disease biology, creating immunotherapies, and improving computational prediction tools. Existing antigen discovery tools are limited in scale; they allow screens of a large number of pMHC molecules against a small […]

Viral Vector Engineering for Next-Generation Immunotherapies

Our work on better understanding pMHC-TCR interactions led to our development of RAPTR, a method that uses pMHC-displaying lentiviruses to infect only antigen-specific T cells. In addition to developing this approach as an antigen discovery tool, we are working to develop new therapeutic strategies that can specifically reprogram immune cells. We are testing the effectiveness […]