Extracellular cues engage discrete cell signaling pathways to activate specific sets of transcription factors, which trigger distinct gene-expression programs. However, these pathways are known to be physically and functionally interlinked within the cellular network. More so, in their anatomic niche, mammalian cells receive signals from a variety of stimuli that generate plausible crosstalks between concomitantly activated pathways. Combining biochemistry, genetics, and computational modeling, we have been characterizing these cross-regulatory mechanisms and elucidating their role in physiology and diseases. We are particularly investigating how the so-called “immune-organogenic” noncanonical NF-κB pathway crosstalks with inflammatory canonical NF-κB signaling and the anti-viral type1- interferon axis.