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Inositol Signaling Group

Intracellular Signals

Stephen B. Shears, Ph.D.
Stephen B. Shears, Ph.D.
Principal Investigator
Tel (919) 541-0793
Fax (919) 541-1898
shears@niehs.nih.gov
P.O. Box 12233
Mail Drop F2-06
Research Triangle Park, North Carolina 27709
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Research Summary

Stephen B. Shears, Ph.D., is head of the Inositol Signaling Group and holds a secondary appointment in the NIEHS Immunity, Inflammation, and Disease Laboratory. The group’s goal is to unravel the molecular mechanisms of cell-signaling processes mediated by inositol phosphates that mediate organismic defenses and homeostasis. This is a topic that has relevance to immune responses, inflammation, cancer, and metabolic disorders such as diabetes. Thus, we aim to promote the development of new genetic and pharmacological approaches to improving human health and longevity.

Phosphates are a recurring theme in the signaling field because of their ability to provide specificity to a molecule's interactions with other cellular entities. For example, the bulky nature of the phosphate group establishes signaling specificity by imposing geometric constraints on ligand-protein and protein/protein interactions. Additionally, the phosphate's negative charge at physiological pH is attracted to positively charged targets. Here, specificity comes from the participation of multiple ionic and hydrogen bonds.

Inositol polyphosphates - and particularly the pyrophosphorylated versions (IP7/IP8) - represent a highly-specialized example of the recruitment of multiple phosphates to engage in novel mechanisms of cellular regulation. As many as eight phosphates are crammed around the six-carbon, inositol scaffold, thereby creating the most concentrated three dimensional arrays of phosphate groups found in Nature. The Inositol Signaling Group has particular strengths in this area of research that has enabled us to make a number of important technical and conceptual advances.

Our laboratory takes a multidisciplinary approach, utilizing techniques from the fields of biochemistry, molecular biology, confocal and FRET microscopy, flow cytometry, surface plasmon resonance, HPLC, and structural biology. This helps us extend our understanding of the roles of inositol phosphates in many different aspects of human biology. This multidisciplinary environment also offers post-doctoral trainees opportunities to expand their expertise.

Shears received his Ph.D. in 1979 from the University of York in the U.K. He has published over 180 articles in the leading scientific journals.

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