Cell growth, differentiation, survival and apoptosis can be regulated by cytokines, growth factors and cellular stresses that trigger distinct as well as overlapping signaling pathways. Abnormal signaling is associated with human cancer. The overall research interest in Dr. Ke Shuai's laboratory is to study cellular signal transduction pathways in normal and tumor cells. These studies may provide novel therapeutic targets for cancer treatment.
Shuai's work is currently centered in two areas. First, Shuai studies the role of PIAS (protein inhibitor of activated STAT) proteins in cellular signaling. In studies aimed at the understanding of cytokine-activated JAK-STAT signaling pathway, Shuai's laboratory has discovered the PIAS family of proteins, which can inhibit the activity of STATs. In addition, PIAS proteins have also been shown to possess SUMO (small ubiquitin-related modifier) E3 ligase activity and can regulate a number of other transcription factors, including p53 and androgen receptor. Shuai and his colleagues are studying the molecular mechanism, the regulation and the biological roles of PIAS proteins in cellular signaling using a combined biochemical and genetic approach.
Secondly, Shuai studies the regulation of the JAK-STAT signaling pathway. Cytokines bind to their cell surface receptors to activate signal transduction pathways that regulate numerous fundamental cellular processes, including cell growth and differentiation, as well as immune and inflammatory responses. The JAK-STAT pathway is widely utilized by many cytokines and is regulated at multiple steps. The study on the regulation of the JAK-STAT pathway is important since abnormal JAK-STAT signaling is associated with immune diseases and cancers. Shuai's laboratory is studying several regulatory mechanisms in the JAK-STAT pathway, including the dephosphorylation of STATs by protein tyrosine phosphatases and the regulation of the JAK-STAT pathway upon viral infection.
Selected Cancer-Related Publications:
Tahk S, Liu B, Chernishof V, Wong KA, Wu H, Shuai K. Control of specificity and magnitude of NF-kappa B and STAT1-mediated gene activation through PIASy and PIAS1 cooperation. Proc. Natl. Acad. Sci. USA. 2007; 104(28):11643-8.
Liu B, Yang Y, Chernishof V, Loo RR, Jang H, Tahk S, Yang R, Mink S, Shultz D, Bellone CJ, Loo JA, Shuai K. Proinflammatory stimuli induce IKKalpha-mediated phosphorylation of PIAS1 to restrict inflammation and immunity. Cell. 2007; 129(5): 903-14.
Shuai K, Liu B. Regulation of gene-activation pathways by PIAS proteins in the immune system. Nat Rev Immunol. 2005; 5(8): 593-605.
Liu B, Mink S, Wong KA, Stein N, Getman C, Dempsey PW, Wu H, Shuai K. PIAS1 selectively inhibits interferon-inducible genes and is important in innate immunity. Nat Immunol. 2004; 5(9): 891-8.
Chung CD, Liao J, Liu B, Rao X, Jay P, Berta P, Shuai, K. Specific inhibition of Stat3 signal transduction by PIAS3. Science. 1997; 278:1803-1805.