Mechanisms underlying cell death in the central nervous system: the interplay between excitotoxicity and inflammation with a particular focus on astrocyte/neuron interactions. Molecules of interest include inducible forms of nitric oxide (NO) synthase and cyclooxygenase (COX), L-12/15 lipoxygenase (12/15 LO) and IL-1ß. The role of astrocyte system xc- (cystine/glutamate transporter) to injury and protection is also being explored. Both in vitro and in vivo models of injury are employed taking a "molecules to mouse" and "mouse to molecules" approach.
Research in Dr. Sandra Hewett's lab focuses on elucidating the molecular and biochemical mechanisms by which post-ischemic inflammation contributes to the progression of acute neuronal injury with a focus on astrocyte-neuron interactions. Studies have determined that the brain damage associated with acute injury ―most commonly caused by cerebral ischemia, head trauma or seizure ― is mediated by over-stimulation of excitatory amino acid (EAA) receptors as well as inflammatory factors. While inflammatory cells from the periphery contribute to neuronal damage there is evidence that inflammatory genes expressed in parenchymal cells of the CNS also play a deleterious role. Molecules of interest in her lab include inducible forms of nitric oxide (NO) synthase and cyclooxygenase (COX), L-12/15 lipoxygenase (12/15 LO) and IL-1ß. The role of astrocyte system xc- (cystine/glutamate transporter) in injury and protection is also being explored. Both in vitro and in vivo models of injury are employed taking a “molecules to mouse” and “mouse to molecules” approach to the essential questions posed.
The Interdisciplinary Neuroscience Group at SU enhances the breadth and depth of training of multiple scientific disciplines. Our training faculty's research expertise is broad, incorporating molecular, cellular, developmental, systems, behavioral, and cognitive neuroscientific approaches to investigate basic, pre-clinical, translational, and clinical questions to unravel the relationship between brain and behavior. Interdisciplinary neuroscience research faculties reside in departments in The College of Arts and Science, The School of Education, The David B. Falk College of Sports and Human Dynamics, and The L.C. Smith College of Engineering and Computer Science.
- Ph.D., Michigan State University
- B.S., Providence College
Also see complete PubMed listings.
- Ann Massie, Severine Boillee, Sandra Hewett, Lori Knackstedt and Jan Lewerenz. Main path and byways: non-vesicular glutamate release by system xc- as an important modifier of glutamatergic neurotransmission. Journal of Neurochemistry 2015 Accepted Article DOI: 10.1111/jnc.13348
- Evonuk KS, Baker BJ, Doyle RE, Moseley CE, Sestero CM, Johnston BP, De Sarno P, Tang A, Gembitsky I, Hewett SJ, Weaver CT, Raman C, DeSilva TM.
Inhibition of System Xc- Transporter Attenuates Autoimmune Inflammatory Demyelination. J Immunol. 2015 Jul 15;195(2):450-63. doi: 10.4049/jimmunol.1401108. Epub 2015 Jun 12.
- He Y, Jackman NA, Thorn TL, Vought VE, Hewett SJ. (2015) Interleukin-1β protects astrocytes against oxidant-induced injury via an NF-κB-Dependent upregulation of glutathione synthesis. Glia. 2015 Apr 16. doi: 10.1002/glia.22828. [Epub ahead of print]
- Lewerenz, J., Hewett, S.J., Huang, Y., Lambros, M., Gout, P.W., Kalivas, P., Massie, A., Smolders, I., Methner, A., Pergande, M., Smith, S.B., Ganapathy, V., and Maher, P. (2013) The cystine/glutamate antiporter system xc- in health and disease: from molecular mechanisms to novel therapeutic opportunities. Antioxidants and Redox Signaling 18: 522-555.
- Hewett, S.J., Jackman, N.A., Claycomb, R.J. (2012) Interleukin-1β in Central Nervous System Injury and Repair European Journal of Neurodegenerative Diseases 1 (2): 195-211. 10.1089/ars.2011.4391.
- Hewett JA, Hewett SJ. (2012) Induction of nitric oxide synthase-2 expression and measurement of nitric oxide production in enriched primary cortical astrocyte cultures. Methods Mol Biol. 814:251-63.
- Uliasz TF, Hamby ME, Jackman NA, Hewett JA, Hewett SJ. (2012) Generation of primary astrocyte cultures devoid of contaminating microglia. Methods Mol Biol. 814:61-79.
- Jackman, N.A., Melchior, SE, Hewett, J.A, Hewett, S.J. (2012) Non-cell autonomous influence of astrocyte system xc- on hypoglycemic neuronal cell death ASN Neuro 4 (1):art:e00074.doi:10.1042/AN20110030 PMC 3275339.
- Claycomb RJ, Hewett SJ, Hewett JA. (2012) Neuromodulatory role of endogenous interleukin-1β in acute seizures: possible contribution of cyclooxygenase-2. Neurobiol Dis. 45(1):234-42.
- Sen E, Basu A, Willing LB, Uliasz TF, Myrkalo JL, Vannucci SJ, Hewett SJ, Levison SW. (2011) Pre-conditioning induces the precocious differentiation of neonatal astrocytes to enhance their neuroprotective properties. ASN Neuro. 2011 Jul 26;3(3):e00062. doi: 10.1042/AN20100029.
- Claycomb RJ, Hewett SJ, Hewett JA. (2011) Prophylactic, prandial rofecoxib treatment lacks efficacy against acute PTZ-induced seizure generation and kindling acquisition. Epilepsia. 52(2):273-83.
- Jackman NA, Uliasz TF, Hewett JA, Hewett SJ (2010) Regulation of System xc- Activity and Expression in Astrocytes by Interleukin-1b: Implications for Hypoxic Neuronal Injury. Glia. 2010 Jul 19. PMID: 20645408 [PubMed-as supplied by publisher]
- Hamby ME, Hewett JA, Hewett SJ. (2010) Smad3-dependent signaling underlies the TGF-β1-mediated enhancement in astrocytic iNOS expression. Glia. 2010 Aug 15;58(11):1282-91. PMID: 20607716 [PubMed - in process]
- Chi-un C, Lewerenz J, Fischer, G., Uliasz, T.F. Espey, M.G., Hummel, F. C, King, B., Schwedhelm, E., Böger, R.H., Gerloff, R. Hewett, S.J., Magnus, T., Donzelli, S. (2009) HNO exacerbates ischemic cerebral injury and oxidative neurotoxicity. Journal of Neurochemistry 110: 1766-1773.
- Hamby, M.E., Hewett, J.A. and Hewett, S. J. (2008) TGF-β1 reduces the heterogeneity of astrocytic cyclooxygenase-2 and nitric oxide synthase-2 gene expression in a stimulus-independent manner. Prostaglandins and other lipid mediators 85:115-124.
- Hamby, M.E., Gragnolati, A.R., Hewett, S.J. and Hewett, J.A. (2008) TGF-β1 and TNFα potentiate astrocytic nitric oxide production by recruiting distinct sub-populations of astrocytes to express NOS-2. Neurochem. Int. 52: 962-971.
- Taylor. A.L.,Bonventre, J.V., Hewett, J.A., Hewett, S.J. (2008) Cytosolic phospholipase A2α inhibition prevents neuronal NMDA receptor-stimulated arachidonic acid mobilization and prostaglandin production but not subsequent cell death Journal of Neurochemistry 106: 1828-1840.
- Fogal, B. Li, J., Lobner, D., McCullough, L.D. and Hewett, S.J. (2007) System xc- activity and astrocytes are necessary for IL-1?-mediated hypoxic neuronal injury. Journal of Neuroscience 27: 10094-10105.
(June 11, 2018)
Sandra and James Hewett will explore physiological mechanisms governing excitatory, inhibitory balance in brain
(March 21, 2017)
Registration and Abstract Submission Deadline Is March 24
(Sept. 6, 2016)
Director of Interdisciplinary Neuroscience Studies mentors scientists from undergrad to professional