Work in the Rajsbaum laboratory focuses on the study of host-pathogen
interactions and innate immune responses to viruses. Innate and
cell-intrinsic immune responses are essential to protect host cells
against pathogens. Members of the tripartite motif
(TRIM) family of E3-ubiquitin ligases are involved in antiviral
immunity by directly inhibiting viral replication or by sensing and
transmitting signals to induce antiviral cytokines. However, to
establish productive infection, viruses have developed
sophisticated mechanisms to counteract host immune responses,
including targeting TRIM proteins. Our lab is interested in elucidating
the mechanisms by which TRIM proteins and other signaling molecules
regulate antiviral functions and how viruses
(Influenza, dengue, Zika, West Nile, Ebola, Nipah and other viruses)
evade these immune responses. We and others have shown that members of
the TRIM family (TRIM5, TRIM6, TRIM25) catalyze the synthesis of
unanchored polyubiquitin chains that activate
antiviral signaling pathways. In addition, new evidence indicates
that TRIMs and ubiquitination of viral proteins can have both antiviral
and proviral functions depending on the host environment. Our lab aims
to dissect these molecular mechanisms
that regulate virus replication using in vitro biochemical methods,
primary immune cells, and in vivo animal models. We also hope to
identify new components of innate immune signaling pathways and viral
factors that could be targeted for therapeutic
intervention.