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.
- Sears, S.M.S. and *Hewett, S.J. (2021) Influence of Glutamate and GABA Transport on Brain Excitatory/Inhibitory Balance Experimental Biology and Medicine PMID: 33554649 DOI: 10.1177/1535370221989263.
- *Hewett SJ, Prado VF, Robinson MB. (2021) The brain in flux: Genetic, physiologic, and therapeutic perspectives on transporters in the CNS Neurochem Int. 2021 Mar;144:104980. doi: 10.1016/j.neuint.2021.104980
- Sears, S. M.S, Roberts, S.H. and *Hewett, SJ. (2021) Hyperexcitability and Structural Sex Differences in Brain of Mice Lacking the Cystine/Glutamate Antiporter, System xc-. Journal of Neuroscience Research Journal of Neuroscience Research DOI: 10.1002/jnr.24971
- H.M.Sosnoski, S.M.S Sears, Y He, C Frare *S. J. Hewett (2020) Sexually dimorphic and brain region-specific transporter adaptations in system xc− null mice Neurochemistry International 121: 104888 https://doi.org/10.1016/j.neuint.2020.104888
- Sears, S.M.S, Hewett, JA and *Hewett, SJ (2019) Decreased epileptogenesis in mice lacking the System xc- transporter occurs in association with a reduction in AMPA receptor subunit GluA1 Epilepsia Open 2019;4:133–143. https://doi.org/10.1002/epi4.12307
- Chowdhury, T. Allen, M.A., Thorn, T.A., He, Y. and *Hewett, S.J.(2018) Interleukin-1β protects neurons against oxidant-induced injury via promotion of astrocyte glutathione production. Antioxidants 7(8), 100; doi:10.3390/antiox7080100.
- Kanzler, M.A., Van Dyke, A.M., He, Y., Hewett, J.A., *Hewett, S.J. (2018) Mice lacking L-12/15-lipoxygenase show increased mortality during kindling despite demonstrating resistance to epileptogenesis. Epilepsia Open 3(2):255–263. doi:10.1002/epi4.12221
- Wilson, J. H., Criss, A.H., Spangler, S., Walukevich, K, Hewett, S. (2017) Analysis of acute naproxen administration on memory in young adults: A randomized double-blind placebo–controlled study. Journal of Psychopharmacology. Oct;31(10):1374-1376. Doi/10.1177/0269881117724406
- He, Y, Akumuo, R.C., Yang,Y., Hewett, S.J. (2017) Mice deficient in L-12/15 lipoxygenase show increased vulnerability to 3-nitropropionic acid neurotoxicity. Neuroscience Letters 643, 65-69. PMCID: PMC5383203
- Hewett, SJ, Shi, J., Gong, Y., Dhandapani, K, Pilbeam, C., *Hewett, JA (2016) Spontaneous Glutamatergic Synaptic Activity Regulates Constitutive COX-2 Expression in Neurons: OPPOSING ROLES FOR THE TRANSCRIPTION FACTORS CREB (cAMP RESPONSE ELEMENT BINDING) PROTEIN AND Sp1 (STIMULATORY PROTEIN-1) Journal of Biological Chemistry 291 (53), 27279-27288. PMCID: PMC5207154
- Shi, J., He, Y., *Hewett, SJ, *Hewett, JA (2016) Interleukin 1β regulation of the system xc-substrate-specific subunit, xCT, in primary mouse astrocytes involves the RNA-binding protein HuR Journal of Biological Chemistry Neurobiology J. Biol. Chem (4), 1643-1651. PMCID: PMC4722447
- Thorn TL, He Y, Jackman NA, Lobner D, Hewett JA,* Hewett SJ. (2015) A Cytotoxic, Co-operative Interaction Between Energy Deprivation and Glutamate Release From System xc- Mediates Aglycemic Neuronal Cell Death. ASN Neuro. 2015;7(6). pii: 1759091415614301. doi: 10.1177/1759091415614301. PMC4641554
- 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
(Dec. 18, 2020)
Assistant Professor Carlos Castañeda is studying the regulation of liquid-like protein droplets in hopes of determining what causes diseases like ALS.
(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