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 Publications
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.
 View more publications, see
Pubmed listing. |
