Research Interests

We have eludicated the role of JAKs (Janus kinases) and STATs (signal transducers and activators of transcription) in interferon (IFN) signaling pathways using biochemical and genetic techniques. The JAKs, tyrosine kinases that associate with the receptors, catalyze IFN-dependent phosphorylation of themselves, the receptors, and the STATs. Phosphorylated STATs trigger transcription of IFN-regulated genes. These mechanisms operate in many other signaling pathways activated by a wide range of growth factors and cytokines. We have isolated 8 different mutant human fibrosarcoma cell lines. Seven of these are defective in JAK-STAT components essential for responses to IFN-alpha or IFN-gamma and are complemented by TYK2, JAK1, or JAK2, or the transcription factors p48, STAT1, or STAT2, or subunits of the IFN-alpha and -gamma receptors. Our long-term goal is to understand how STATs are activated and how they initiate transcription of their target genes in response to different extracellular signaling proteins. We are also identifying components of other signaling pathways, using a combination of biochemical and genetic techniques. One example is the pathway that begins with DNA damage or arrest of DNA synthesis and ends with induction of functional p53 protein. Another is the pathway through which tumor necrosis factor alpha regulates gene expression.

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Primary Section

Section 21: Biochemistry

Secondary Section

Section 22: Cellular and Developmental Biology