Affiliations

Professor, Hematology-Oncology, Biological Chemistry

Member, Gene Regulation GPB Home Area, Immunity, Microbes & Molecular Pathogenesis GPB Home Area, JCCC Signal Transduction and Therapeutics Program Area

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. The overall research interest in Dr. Ke Shuai’s laboratory is to study the molecular mechanisms of cell signaling, and how altered signaling events contribute to the development of human diseases such as cancers and immune disorders. Our work is currently focused on understanding the role of the PIAS (protein inhibitor of activated STAT) protein family in the regulation of various cellular responses. PIAS proteins were originally identified in our laboratory as negative regulators of STATs (signal transducer and activator of transcription). PIAS proteins possess SUMO (small ubiquitin-related modifier) E3 ligase activity that function to promote the sumoylation of various protein molecules involved in gene regulation. We are interested in studying the molecular mechanisms, the regulation, and the biological roles of PIAS proteins in cellular signaling using a combined biochemical and genetic approach. Our most recent studies indicate that PIAS1 is recruited to chromatin upon stimulation by a variety of signals, including cytokines, growth factors and TCR activation. The binding of PIAS1 to chromatin promotes the formation of a repressive chromatin state, resulting in the epigenetic silencing of PIAS1-target genes. PIAS1 acts by recruiting chromatin modification enzymes including DNA methyl transferases (DNMTs) and HP1 to gene promoters. The importance of this newly identified PIAS1 epigenetic regulatory pathway is being actively investigated in our laboratory.

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