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Faculty James Hewett
Assistant Professor of Neuroscience
Associate
Director, Graduate Program in Neuroscience
jhewett@nso1.uchc.edu
Areas of Interest: central nervous system; inflammation;
arachidonic acid metabolism; therapeutics; gene expression; cell
culture.
In general, this laboratory studies mechanisms of inflammatory
central nervous system (CNS) injury. A major specific focus of the
laboratory is on the actions of prostaglandin H synthases (PGHSs) within
the central nervous system (CNS). PGHSs catalyze the metabolism of
arachidonic acid to bioactive lipids, including prostaglandins,
thromboxanes, and prostacyclin. They are key therapeutic targets, being
the primary sites of action of nonsteroidial anti-inflammatory drugs (NSAIDS),
including aspirin and ibuprofen, which inhibit PGHS catalytic activity.
Research projects in the laboratory employ animal models together with
pharmacological and genetic tools to study the consequences of
arachidonic acid metabolism in the CNS under certain pathological
conditions. Related biochemical studies employ cell culture models to
examine aspects of the regulation of PGHS activation and inactivation at
the subcellular level.
Publications
Selected References:
Hamby ME, Gragnolati AR, Hewett SJ, Hewett JA.TGFbeta1 and TNFalpha
potentiates nitric oxide production in astrocyte cultures by recruiting
distinct subpopulations of cells to express NOS-2.Neurochem Int. 2008
May;52(6):962-71.
Hamby ME, Hewett JA, Hewett SJ.TGF-beta1 reduces the heterogeneity of
astrocytic cyclooxygenase-2 and nitric oxide synthase-2 gene expression
in a stimulus-independent manner. Prostaglandins Other Lipid Mediat.
2008 Mar; 85(3-4):115-24.
Hewett SJ, Silakova JM, Hewett JA. Oral treatment with rofecoxib
reduces hippocampal excitotoxic neurodegeneration.J Pharmacol Exp Ther.
2006 Dec;319 (3):1219-24.
Hamby, ME, Hewett, SJ, and Hewett, JA. (2006) Purification of primary
astrocyte cultures: A rapid procedure for the removal of microglia. J.
Neurosci. Methods 150: 128-137.
Hamby, M.E., Hewett, J.A., Hewett, S.J. (2006) TGF-b1 potentiates
astrocytic nitric oxide production by expanding the population of
astrocytes that express NOS-2. Glia 54(6):566-77.
Hewett, S.J., Bell, S.C. and Hewett, J.A. (2006) Contributions of
cyclooxygenase-2 to neuroplasticity and neuropathology of the central
nervous system. Pharmacology and Therapeutics 112(2):335-57.
Hewett, S.J., Silakova, J.M., and Hewett, J.A. (2006) Oral treatment
with rofecoxib reduces hippocampal excitotoxic neurodegeneration. J.
Pharmacol and Exp Ther. 319(3):1219-24
Fogal B, Hewett JA, Hewett SJ. (2005) Interleukin-1beta potentiates
neuronal injury in a variety of injury models involving energy
deprivation. J Neuroimmunol. 161(1-2):93-100.
Snipes JA, Kis B, Shelness GS, Hewett JA, Busija DW. (2005) Cloning
and characterization of cyclooxygenase-1b (putative cyclooxygenase-3) in
rat. J Pharmacol Exp Ther. 313(2):668-76.
Silakova JM, Hewett JA, Hewett SJ. (2004) Naproxen reduces
excitotoxic neurodegeneration in vivo with an extended therapeutic
window. J Pharmacol Exp Ther. 309(3):1060-6.
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