James E. Darnell, Jr.

The Rockefeller University

Election Year: 1973
Primary Section: 22, Cellular and Developmental Biology
Secondary Section: 21, Biochemistry
Membership Type: Member

Research Interests

Two central tenets underlie most of the research in our group. The first is that differentiation and development are dependent on the execution of a correct transcriptional program in particular cells which leads to the second, that the signals which cells receive and interpret to execute such programs come in large part from polypeptides that bind to the cell surface. In past years, we studied adult and developing hepatocytes and transcription factors that participate in the "liver cell" phenotype. At present, the majority of the laboratory group studies how signals from the cell surface affect nuclear transcription. These studies originally used alpha and gamma interferon stimulation of transcription and uncovered a group of latent cytoplasmic proteins termed STATs (for "signal transducers and activators of transcription") that become active as DNA-binding factors only after an interferon occupies its receptor. Molecular clones were obtained for the proteins and antisera to these proteins allowed the demonstration that interferon-dependent tyrosine phosphorylation followed by dimerization of the proteins is the basis for activation. Most recently this pathway has been found to operate in transcriptional signals for many ligands other than the interferons and a Drosophila Stat that functions in early development was found. The pathway appears to serve a very general role in conducting signals from the cell surface to the nucleus after binding of many different polypeptides both in early development and in maintaining homeostasis in adults. The functional domains of STAT proteins and how the activation-inactivation cycle is carried out are under study.

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