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NINDSNIMHNICHDNIDCDNEINIDCRNIANIAAANIDANHGRI NCCIHNIDDKNIEHSCCB

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Senior Investigator

Stephen B. Shears, D.Phil.

Laboratory of Signal Transduction
MD F2-06
Research Triangle Park NC 27709-
Office: (919) 541-0793

Fax: (919) 541-1898
shears@niehs.nih.gov

Dr. Shears earned his Ph.D. in Biology in 1979 at the University of York (U.K.), where he examined the regulation of mitochondrial transmembrane proton fluxes by thyroid hormone. During an MRC Research Fellowship at the University of Birmingham, he studied the metabolism of inositol trisphosphate, an "off-switch" for cell signaling by certain calcium channels. In 1988, Dr. Shears joined NIEHS to head the Inositol Signaling Section, where he has studied the roles of inositol phosphates and inositol lipids in signal transduction. His current interests include the control of chloride ion channels by inositol phosphates (in both excitable and non-excitable cells) and the regulation of cellular energy homeostasis by inositol pyrophosphates.



One of our research topics is to study the mechanisms by which inositol phosphates regulate calcium-activated chloride conductance in both excitable and non-excitable cells. We also study the roles of inositol pyrophosphates in the regulation of cellular energy homeostasis, particularly in organs with high metabolic rates, such as brain and skeletal muscle. These two projects underpin the over-arching goal of understanding the spatial dynamics of intracellular communication. It is this intracellular compartmentalization of signaling entities that ensures the appropriate degree of specificity of cellular responses. We study the molecular basis for compartmentalization.

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  • 1) Gokhale, N., Zaremba A., Shears S.B. (2011)
  • Receptor-dependent compartmentalization of PPIP5K1, a kinase with a cryptic polyphosphoinositide binding domain
  • Biochem. J, 434, 415-426
  • 2) Shears, S.B (2009)
  • Diphosphoinositol Polyphosphates: Metabolic Messengers?
  • Mol. Pharm, 76, 236-252
  • 3) Mitchell, J., Wang, X., Gentsch, M., Nelson, D.J. and Shears, S.B (2008)
  • An Expanded Biological Repertoire for Ins(3,4,5,6)P4 through its Modulation of ClC-3 Function
  • Current Biology , 18, 1600-1605
  • 4) Yang, L., Reece, J.M., Cho, J., Bortner, C. Shears, S. B. (2008)
  • The Nucleolus Exhibits an Osmotically Regulated Gatekeeping Activity That Controls the Spatial Dynamics and Functions of Nucleolin
  • J. Biol. Chem, 283, 11823-11831
  • 5) Choi, K., Mollapour, E.M., Choi, J.H. and Shears, S.B. (2008)
  • Cellular energetic status supervises the synthesis of bis-diphosphoinositol tetrakisphosphate ("InsP8")
  • Mol. Pharm, 74, 527-536
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