Neuroscience and central nervous system neurobiology and pathology, neuromodulators and epilepsy, arachidonic acid metabolism and cyclooxygenase-2, cytokines and interleukin-1β, signal transduction and gene expression, animal models, transgenic mice, cell culture, pharmacology.

Research Spotlight

Neuromodulators are substances that influence information processing and transfer within the nervous system. In general, the research in my laboratory explores the function of endogenous neuromodulatory mechanisms activated within the brain under pathological conditions, with a particular interest in epilepsy. Epilepsy is a debilitating disorder of the brain whereby groups of neurons become prone to abnormal hyperexcitability, provoking episodes of spontaneous seizure behavior. The prevalence of epilepsy in the general population is ~1% and brain injury can increase the risk of acquiring the malady by 10-30 times depending on the nature of the injury. Cures and preventative measures remain elusive and the incidence of resistance to current antiepileptic drugs is a serious clinical limitation to the effective treatment of patients who suffer from epilepsy. We reason that a better understanding of the function of endogenous neuromodulatory mechanism in epilepsy may identify novel therapeutic targets for new antiepileptic drug development.

BIO 457 - Principles of Human Toxicology

College of Arts and Sciences

3 credit(s) At least 1x fall or spring

Crosslisted with: FSC 457
Double Numbered with: BIO 657
This course examines key aspects of human toxicology, including dose-response relationships, absorption, distribution, biotransformation, elimination, toxicokinetics, molecular mechanisms of toxicity, pesticides, metals, and toxic responses in specific organ systems. Additional work required of graduate students.
PREREQ: BIO 327 AND CHE 275 AND MAT 285

BIO 444 - Seminar in Neurotoxicology

College of Arts and Sciences

3 credit(s) At least 1x fall or spring

Double Numbered with: BIO 644
Examination of the mechanisms and consequences of toxicity of poisons in the central and peripheral nervous systems with a focus on the primary research literature. Additional work is required of graduate students.
PREREQ: BIO 211

• Uliasz, T.F., Hamby, M.E.(*), Jackman, N.A.(*), Hewett, J.A., and Hewett, S.J. Generation of primary astrocyte cultures devoid of contaminating microglia. Methods Mol. Biol. 814: 61-79, 2012.
• Hewett J.A. and Hewett S.J. Induction of nitric oxide synthase-2 expression and measurement of nitric oxide production in enriched primary cortical astrocyte cultures. Methods Mol. Biol. 814: 251-263, 2012.
• Claycomb, R.J.(*), Hewett, S.J., and Hewett, J.A. Anticonvulsant properties of endogenous interleukin-1β: possible contribution of cyclooxygenase-2. Neurobiol. Dis., 45:234-42, 2012.
• Claycomb, R.J.(*), Hewett, S.J., and Hewett, J.A. Characterization of the effect of oral rofecoxib treatment on PTZ-induced acute seizures and kindling. Epilepsia 52:273-283, 2011.
• Hamby, M.E.(*), Hewett, J.A., and Hewett, S.J. Smad3-dependent signaling underlies the TGF-β1-mediated enhancement in astrocytic iNOS expression. Glia 58:1282-1291, 2010.
• Hewett, J.A. Determinants of regional and local diversity within the astroglial lineage of the normal central nervous system. J. Neurochem. 110:1717-1736, 2009. (REVIEW)
• Hamby, M.E., Gragnolati, A.R.(*), Hewett, S.J., Hewett, J.A. TGFbeta1 and TNFalpha potentiates nitric oxide production in astrocyte cultures by recruiting distinct subpopulations of cells to express NOS-2. Neurochem. Int. 52:962-71, 2008.
• Hamby, M.E.(*), Hewett, J.A., Hewett, S.J. 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. 85:115-24, 2008.
• Hewett, S.J., Silakova, J.M., and Hewett, J.A. Oral treatment with rofecoxib reduces hippocampal excitotoxic neurodegeneration. J. Pharmacol. Exp. Ther. 319:1219-1224, 2006.
• Hamby, M.E.(*), Hewett, S.J., and Hewett, J.A. Purification of primary astrocyte cultures: A rapid procedure for the removal of microglia. J. Neurosci. Methods 150:128-137, 2006.
• Hamby, M.E.(*), Hewett, J.A., Hewett, S.J. TGF-b1 potentiates astrocytic nitric oxide production by expanding the population of astrocytes that express NOS-2. Glia 54:566-577, 2006.
• Hewett, S.J., Bell, S.C. and Hewett, J.A. Contributions of cyclooxygenase-2 to neuroplasticity and neuropathology of the central nervous system. Pharmacol. Ther. 112:335-357, 2006. (REVIEW)
• Silakova, J.M., Hewett, J.A., and Hewett, S.J. Naproxen reduces excitotoxic neurodegeneration in vivo with an extended therapeutic window. J. Pharmacol. Exp. Ther. 309:1060-1066, 2004.
• Hewett, S.J., Uliasz, T.F., Vidwans, A.S., and Hewett, J.A. Cyclooxygenase-2 contributes to N-methyl-D-aspartate-mediated neuronal cell death in primary cortical cell culture. J. Pharmacol. Exp. Ther. 293:417-425, 2000.
• Hewett, J.A., Hewett, S.J., Winkler, S., and Pfeiffer, S.E. Inducible nitric oxide synthase expression in cultures enriched for mature oligodendrocytes is due to microglia. J. Neurosci. Res. 56:189-198, 1999.
• Hewett, J.A. and Roth, R.A. The coagulation system, but not circulating fibrinogen, contributes to liver injury in rats exposed to lipopolysaccharide from gram-negative bacteria. J. Pharmacol. Exp. Ther. 272:53-62, 1995.
• Hewett, J.A., Jean, P.A., Kunkel, S.L., and Roth, R.A. Relationship between tumor necrosis factor-alpha and neutrophils in endotoxin-induced liver injury. Am. J. Physiol. 265:G1011-1015, 1993.
• Hewett, J.A. and Roth, R.A. Hepatic and extrahepatic pathobiology of bacterial lipopolysaccharides. Pharmacol. Rev. 45:382-411, 1993. (REVIEW)
• Hewett, J.A., Schultze, A.E., VanCise, S.(*), and Roth, R.A. Neutrophil depletion protects against liver injury from bacterial endotoxin. Lab. Invest. 66:347-361, 1992.

(*) mentored student

• Warnecke, A. (*), Schuch, K. (*), Gladstone-Helak, M., Hassett, J., Hewett, J.A. Maternal exposure to a DDT-like environmental contaminant during gestation predisposes adult offspring to seizures. American Society for Neuroscience, #PTW01-07, 2016.
• Groden, P.J.(*), Gong, Y.(*), Wang, W.(*), Gladstone, M.B., and Hewett, J.A. Transgenic approaches to induce overexpression of cyclooxygenase-2 in discrete neuronal subpopulations of the brain. Am Soc Neurochem, #PS09, 2014.
• Gong, Y.(*), Wang, W.(*), and Hewett, J.A. Developmental and NMDA receptor-dependent mechanisms contribute to changes in expression of prostaglandin E synthase isozymes in cultures of cortical neurons. Soc Neurosci, #231.17, 2013.
• Hewett, J.A., Katrin Andreasson, and Hewett, S.J. Transgenic over-expression of cyclooxygenase-2 (COX-2) in neurons suppresses pentylenetetrazole (PTZ)-induced acute seizure activity and kindling acquisition. Am Epilepsy Soc, #1.015, 2010.

(*) mentored student