Pharmacology & Cancer Biology | Duke University Medical Center

Dr. John York

John York, Ph.D.
Investigator, HHMI
Professor of Pharmacology and Cancer Biology
Professor of Biochemistry

Duke University Medical Center
C203 LSRC
Box 3813
Durham, NC 27710

Phone: 919-681-6414
E-mail: yorkj@duke.edu
Web site: http://www.duke.edu/web/yorklab

Research Interests

Our laboratory focuses on the role of inositol signaling pathways in growth control and in the pharmacologic action of lithium used for the treatment of bipolar disease. Conventional wisdom describes activation of inositol signaling pathways as a means to mobilize calcium through a second messenger, IP3. While this dogmatic view is widely accepted, it is oversimplified, and does not account for why the cell produces over 30 inositol polyphosphate (IP) molecules, the majority of which have not been studied as messengers. It is our hypothesis that such IPs, designated as orphans, may have equally important signaling roles. Thus we have focused on expanding the view of the pathway and have identified cellular components and processes influenced by orphan IP messengers. To accomplish this, the laboratory has adopted a unique multidisciplinary approach that bridges molecular and cellular biology, pharmacology, biochemistry, genetics, and X-ray crystallography. Our studies have defined novel signaling roles for orphan IPs in regulating membrane trafficking, cytoskeletal organization, gene expression and mRNA export, and have uncovered a novel family of lithium targets with potential relevance to manic depressive disease. In addition, our work has uncovered that nuclear specific compartmentalization of inositol signaling is important for growth control and cellular function.

Publications

Mulugu, S, Bai, W., Fridy, P, Otto, J.C., Dollins, E.C., Haystead, T.A., Ribeiro, A, and York, J.D. (2007). A conserved family of enzymes that phosphorylate inositol hexakisphosphate. Science, 316, 106-109.

Lee, Y-S, Mulugu, S, York, J.D. and O'Shea, E.K. (2007) Regulation of a Cyclin/CDK/CDK Inhibitor Complex by Inositol Pyrophosphates. Science, 316, 109-112.

Otto, J. C., Kelly, P., Chiou, S. T. and York, J. D. (2007) Alterations in an inositol phosphate code through synergistic activation of G-protein and inositol phosphate kinases Proc Natl Acad Sci U S A, 104, 15653-15658.

Frederick , J.P., Mattiske, D., Wofford, J.A., Drake, L.Y., Chiou, S.T., Hogan, B.L.M., York, J.D. (2005) An essential role for an inositol polyphosphate multikinase, Ipk2, in mouse embryogenesis and second messenger production. Proc Natl Acad Sci U S A, 102, 8454-8459.

Stevenson-Paulik, J., Bastidas, R.J, Chiou, S.T., Frye, R.A. and York , J.D. (2005) Generation of phytate-free seeds in Arabidopsis through disruption of inositol polyphosphate kinases. PNAS, 102, IN PRESS.

York , S.J., Armbruster, B.N., Greenwell, P., Petes, T.D. and York , J.D. Inositol diphosphate signaling regulates telomere length (2005) JBC, 280, 4264-4269.

Seeds, A.M., Sandquist, J.C. Spana, E.P. and York , J.D. A Molecular basis for inositol polyphosphate synthesis in Drosophila melanogaster (2004) JBC, 279, 47222-47232.

Odom, A.R., Stahlberg, A., Wente, S.R. and York, J.D. A role for nuclear inositol 1,4,5-trisphosphate kinase in transcriptional control (2000) Science, 287, 2026-2029.

York , J.D., Odom, A.R., Murphy, R.,Ives, E.A. and Wente, S.R. A phospholipase C-dependent inositol polyphosphate kinase pathway required for efficient mRNA export (1999) Science, 285, 96-100.

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