Research in the Ghosh lab focuses on how the Nuclear Factor-kappa B (NF-kappa B / NF-kB) transcription factor family plays such a vital role in mammalian immune responses. We therefore aim to address the following questions:

Why do so many fundamental immunological processes rely on NF-kB?

How does engagement of receptors of the innate and adaptive immune system lead to the activation of immune responses through NF-kB?

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NF-kappa B (NF-kB) plays a critical role in regulating the expression of a large number of genes involved in immune, inflammatory and apoptotic processes.  NF-kappa B can be activated by different stimuli such as microbial products, proinflammatory cytokines, T and B cell mitogens and physical and chemical stresses.  NF-kB in turn regulates the inducible expression of many cytokines, chemokines, adhesion molecules, acute phase proteins and anti-microbial peptides. Therefore NF-kB plays a central, evolutionarily conserved role in coordinating immune and inflammatory responses.

In unstimulated cells, NF-kB is retained in the cytoplasm through its interaction with the inhibitory IkB proteins. Stimulation of cells with different inducers leads to the phosphorylation and subsequent degradation of the IkB proteins. Upon degradation of IkB, the free NF-kB enters the nucleus, however translocation of NF-kB to the nucleus is, in itself, not sufficient to drive transcription of target genes. Instead, specific phosphorylation of one of the NF-kB subunits, p65/RelA, is required for both efficient DNA-binding and transcriptional activity of the nuclear NF-kB.

We wish to understand the mechanisms that operate in the signal transduction pathways that lead to NF-kB and the regulatory mechanisms that control NF-kB in the nucleus. To learn more see the pages that relate to individual projects in the lab or visit our publications page. A detailed overview of all aspects of NF-kB can be found in the recently published Handbook of Transcription Factor NF-kappaB.