Faculty

Shigeki Miyamoto

Co-Director of Cell Signaling Program, Carbone Cancer Center

Shigeki MiyamotoNF-kB signaling in lymphocyte activation and malignancies

The Miyamoto lab is pursuing a variety of research interests focusing on the mechanisms involved in NF-κB signaling and its roles in biological and pathological contexts. NF-κB is a family of evolutionarily conserved transcription factors that are key in normal immune system development, activation of innate/adaptive immunity, embryonic development, and tumor development and progression, among others. The NF-κB family of proteins contains five members in mammals that are widely expressed in different cell types as inactive cytoplasmic complexes.

Miyamoto Research“Activation” of NF-κB is induced by a wide variety of extracellular and intracellular signals, which involves signaling events that lead to the release of an active NF-κB dimer from one of several cytoplasmic inhibitor proteins, IκB’s, and nuclear translocation of NF-κB so that it can activate transcription of different target genes to coordinate the above biological and pathological processes.

Our lab currently addresses the following three overarching questions: (i) how nuclear DNA damage induced by different anticancer agents and endogenous conditions (e.g., V(D)J and class-switch recombination) cause a nuclear-to-cytoplasmic signaling pathway to regulate NF-κB dependent processes, such as cell death or immune cell development/activation, (ii) how NF-κB signaling is constitutively turned on in primary human cancer cells (e.g., multiple myeloma and lymphoma) and how tumor microenvironment components modulate it to promote cancer cell growth and progression, and (iii) how ubiquitin and SUMO (small ubiquitin-related modifier) regulate NF-κB signaling.

We address these questions by employing a variety of experimental strategies, including biochemical, molecular, cellular and genetically modified mouse-based approaches, and by collaborating with multiple investigators with expertise in complimentary areas.

 

View publications by Shigeki Miyamoto on PubMe