Department Directory

Andrew C Larner, Ph.D.

Andrew LarnerProfessor of Biochemistry & Molecular Biology

PO Box 980614
Richmond, VA 23298-0614

Telephone: 804-828-2903

  • M.D., 1981, University of Virginia
  • Ph.D., 1982, University of Virginia

1982-1985, Rockefeller University



The focus of my research for the past 15 years has been to understand the signals that are activated by interferons (IFNs) binding to their cell surface receptors that result in the biological actions of these cytokines. Initially we focused our attention on the cascades that lead to the expression of immediate early genes by incubation of cultured cells with either IFNa/ß (type 1 interferons) or IFNγ (type 2 interferon). The findings from my lab along with several others resulted in the delineation of the Jak/Stat Pathway as a key cascade that regulates the expression of early response genes by not only interferons but also a variety of other cytokines. Interferon activation of the Jak family of tyrosine kinases leads to the tyrosine phosphorylation of both interferon receptor subunits and Stat transcription factors that translocate to the nucleus where they bind enhancers in responsive genes to stimulate their transcription. It is clear from several studies including ones published from my lab that IFN activation of the Jak/Stat pathway is necessary, but not sufficient for the biological actions of these cytokines. In addition to activation of the Jak/Stat pathway, we have shown that interferons also regulate other well-defined signaling cascades including ERK1 and PI-3 kinase. During the past 5 years my research has focused on two areas of interferon biology. One topic concerns changes in the signaling events that control interferon stimulated early response genes in cells that have been previously desensitized to this cytokine. The information from the latter studies has implications in how one chronically administers these and possibly other cytokines for therapy of a variety of diseases such as multiple sclerosis. The other area of interest concerns the regulation of immune responses and cell growth through activation of the Stat3 transcription factor. The current model dictates that binding of cytokines such as interleukin-6 and interleukin-10 to their cell surface receptors induces tyrosine and serine phosphorylation of Stat3 resulting in its nuclear accumulation and binding to a GAS enhancer in the promoters of Stat3-responsive genes. Recent experiments in the lab provide the first evidence for the presence of Stat3 in mitochondria of cultured cells as well as primary tissues including liver and heart. In Stat3 -/- primary pro B cells cellular ATP levels and the activities of complexes I and II of the electron transport chain (ETC) are decreased by 50 - 90%. Stat3 expressed in Stat3 -/- cells, which is targeted to the mitochondria restores the functions of complexes I and II. In mice that do not express Stat3 in the heart there are also selective defects in the activities of these components of the electron transport chain. These data indicate that mitochondrial- localized Stat3 contributes novel functions which may orchestrate responses to cellular stress and innate immunity through modulating the activity of the ETC and the production of ATP. They also suggest that the subcellular localization of a protein can drastically alter its


View Dr. Larner's Publications via the National Library of Medicine's PubMed.


VCU Department of Biochemistry and Molecular Biology Virginia Commonwealth University VCU Medical Center
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