NF-kB plays critical roles in the development of the immune system, in the inflammatory and immune response, and in controlling cell survival and proliferation. As such, it has broad and critical roles in multiple aspects of carcinogenesis and cancer pathogenesis, in determining chemoresistance and cancer progression.
Togehter with Dr. Hoffmann and Dr. Ponomarenko we applied systems biology and data integration methods to functionally related genes and proteins important for NF-kB regulation and signaling.
Molecularly, NF-kB denotes a family of 12 dimeric transcription factors, which are regulated by a family of five inhibitory proteins (IkB) via phosphorylation, protein degradation, processing, complex formation and sub-cellular localization events. Using single and compound knockout mice for each of the NF-kB and IkB genes, Hoffmann’s laboratory characterizes physiological functions of this signaling system and reveal new ones.
In addition, biochemical approaches applied to defined genetic mutants allows the Hoffmanm lab to address the molecular and functional specificities of each of the IkB and NF-kB signal transducers in regulating signal transduction and target gene activation.
We explore the IkB-NF-kB signaling system and reveal critical regulatory mechanisms and hope to identify the molecular causes of cancer-associated misregulation of NF-kB, and potential drug targets to affect specific subsets of NF-kB dimers. We further hope to better understand the multiple cancer-associated roles of NF-kB in inflammation, apoptotis and senescence, the molecular specificities that distinguish them, and reveal potential strategies for therapeutic intervention.