Projects
At any time in the lab, there are numerous projects that are often closely related if not inter-connected. These projects are often collaborative in nature. Current projects and recent representative papers include:
Structural biophysics of T cell specificity
We are using structural biology and experimental and computational biophysics to improve our understanding of the range of targets a given TCR will recognize.
Singh et al., Nature Communications (2022)
Smith et al., Proceedings of the National Academy of Sciences (2021)
Modeling and predicting TCR targets
We are developing ways to model and predict TCR targets from structural and physical principles, using both physics and AI-based computational modeling.
Mikhaylov et al., Structure (2024)
Keller et al., Frontiers in Immunology (2022)
Assessing the role of molecular motion in immune recognition and signaling
We are using experimental and computational techniques to study how molecular flexibility influences recognition in the immune system, as well as how flexibility and motion influences signaling through the T cell membrane.
Ma et al., Journal of Biological Chemistry (2021)
Ayres et al., Frontiers in Immunology (2019)
Engineering immune specificity
We are using the principles of protein design to engineer TCRs to improve on-target specificity and reduce the capacity for off-target recognition, demonstrating ways to improve TCR-based biologics and cell therapies.
Rosenberg et al., Frontiers in Immunology (2024)
Hellman et al., Molecuar Therapy (2018)
Catch bonds in immune recognition
We are developing atomic-level models to understand the mechanism of enigmatic force-dependent “catch bonds” in immune receptors and how these tune molecular recognition as well as biological outcomes.
Ayres et al., Journal of Immunology (2023)
T cell degeneracy in transplantation and autoimmunity
We are applying our expertise in TCR specificity to understand what leads to cross-recognition in transplant rejection and autoimmunity, with a particular focus on the role of prior exposure to pathogens and the corresponding increased risk of immune dysfunction.
Shi et al., Journal of Clinical Investigation (2023)
Khorki et al., Frontiers in Immunology (2023)
Neoantigen based cancer vaccines
We are working to understand the physical features that govern the immunogenicity of neoantigens present in cancer genomes, working to improve the development of personalized cancer vaccines.
Custodio et al., Proceedings of the National Academy of Sciences (2023)