Research Overview
we focus on the evolution of the adaptive immune response against pathogens and how this may inform therapeutic and vaccine development. we also want to know how adaptive responses or therapeutic interventions influence pathogen evolution. we use a combination of biophysical and biochemical techniques to address these questions. our pathogens of interest are skewed to orthomyxo- and flaviviruses, but we also study emerging viruses (e.g., alpha-, arena-, bunya- and filoviruses). we are always open to pursuing new directions and pathogens!
antibody discovery: observation
can we identify antibodies that target conserved sites on viral glycoproteins?
we are interested in using single b-cell sorting to identify antibodies that target conserved sites on viral glycoproteins across model organisms (e.g., murine, bats, humans) in order to understand the evolution of the adaptive immune response.
protein engineering: implementation
can we tinker with viral antigens to elicit a desired immune response?
vaccination approaches have failed for many viral and parasitic diseases. new approaches to rational vaccine design are necessary. we use structure-guided approaches for immunogen design to direct B-cell populations. we test these immunogens in animal models and analyze resulting B-cell repertoires in order to understand potential “rules” that may govern antigenicity and immunogenicity.
viral evolution: consequence
can the evolutionary arms race between host and pathogen be recapitulated in vitro?
pathogens use antigenic variation of their surface-exposed proteins as an evasion strategy to subvert and avoid host immune surveillance. we are broadly interested in understanding the evolution and co-evolution of pathogens with their hosts. in particular, how the adaptive immune system exerts pressure on viral proteins and how viruses evolve to escape such selective pressures. understanding these interactions on a structural level may guide therapeutic intervention and vaccine development. we aim to reconstitute the evolutionary arms race using directed evolution platforms to evolve both antibodies and viruses.
therapeutics: alternatives
can we identify direct-acting antivirals and protein-based therapeutics to inhibit viral entry?
viruses that fuse from internal compartments present a significant hurdle for inhibition. targeting intermediates in the viral fusion pathway requires that the inhibitor be present in the same internal compartment as the fusing virus. we are developing strategies to deliver inhibitors that inhibit conformational rearrangements of viral glycoproteins. we leverage our understanding of the viral fusion pathway to develop assays to identify inhibitors of viral entry.