The Samir Lab studies crosstalk between stress, innate immune, and
programmed cell death signaling in response to pathogenic challenges. We
are using, or willing to use, any tool and the kitchen sink if it can
help.
The innate immune system is the first line of defense
against pathogenic challenges including microbial pathogens. Innate
immune activation can lead to programmed cell death. Uncontrolled
programmed cell death can cause severe disease, and even death.
Pathogenic challenges also activate stress signaling pathways which
can lead to assembly of a membraneless cytoplasmic component called
stress granules. Stress granules have been reported to inhibit
programmed cell death and in the context of viral
infections amplify the type I interferon signaling. Therefore,
stress granule assembly could be a mechanism to restrict uncontrolled
programmed cell while maintaining antiviral state. Interestingly,
Toll-like Receptor (TLR) mediated innate immune
signaling compromises stress granules through the inhibitor of kappa
b kinase complex (IKK complex). This suggests another layer of
interplay between the stress, innate immune and programmed cell
signaling pathways. Our goal is to elucidate molecular
mechanisms that govern this cross regulation and ultimately build
quantitative models that would allow us to design precision therapeutic
interventions.