Vanderbilt University School of Medicine

McLaughlin, BethAnn , Ph.D.
Assistant Professor of Neurology
Assistant Professor of Pharmacology

Lab Url: http://www.mc.vanderbilt.edu/root/vumc.php?site=mclaughlinlab

Phone Number: (615) 936-3847

Email Address:bethann.mclaughlin@vanderbilt.edu

McLaughlin, BethAnn's picture

Office Address   Mailing Address

8110 MRB III

8110 MRB III 465 21st Avenue South 37232-8548


Research Keywords
apoptosis, pharmacology, molecular medicine, stroke, neurodegeneration, neuroprotection, heat shock proteins, kinase, neuroscience, parkinson's disease, transcription, preconditioning, oxidative stress, reactive oxygen species, ion homeostasis,Apoptosis,Biochemistry,Cardiac function,Heart,Ion transport,Kinase,Mass spectroscopy,Membrane,Molecular medicine,Neuroscience,Pharmacology,Phosphorylation,Proteomics,Transcription,Virus

Research Description
My laboratory is interested in studying cell signaling pathways related to neurodegeneration and protection. We have two major research programs ongoing in the lab. The first is the study of how a short, sublethal ischemic event in the brain can lead to subsequent neuronal resistance to a severe stroke, a phenomenon commonly referred to as ischemic preconditioning. In order to investigate the cellular and molecular events that contribute to this process, we have developed several in vivo and in vitro systems in which cortical neuronal cells can be rendered less sensitive to excitotoxic cell death following a nontoxic exposure to mild chemical ischemia or hypoxia. We are using a variety of biochemical, molecular and proteomic approaches to both enhance our understanding of signaling pathways that we have already determined to be critical for the expression of preconditioning as well as to identify new protein targets which may contribute to this phenomenon. Our findings suggest that intervention against neurological events which result in subtoxic activation of traditional cell death pathways may actually increase vulnerability to subsequent stressors.
Other ongoing lab projects include understanding how classical biochemical changes in ion homeostasis (specifically zinc, calcium and potassium homeostasis) induce the molecular pathways associated with apoptotic cell death. In this work we established a novel link between ROS and zinc induced activation of MAPKs and opening of potassium channels that are associated with apoptotic cell death.
The goal of my research program is to understand the endogenous pathways associated with neurodegeneration and protection to develop novel therapeutics for stroke, cerebral palsy and other degenerative conditions. In addition, these studies investigate signaling pathways which provide protective mechanisms against other forms of cell death.

Publications
Alcendor, DJ, Block, FE, Cliffel, DE, Daniels, JS, Ellacott, KL, Goodwin, CR, Hofmeister, LH, Li, D, Markov, DA, May, JC, McCawley, LJ, McLaughlin, B, McLean, JA, Niswender, KD, Pensabene, V, Seale, KT, Sherrod, SD, Sung, HJ, Tabb, DL, Webb, DJ, Wikswo, JP. Neurovascular unit on a chip: implications for translational applications. Stem Cell Res Ther, 4 Suppl 1, S18, 2013.

Gorrindo, P, Lane, CJ, Lee, EB, McLaughlin, B, Levitt, P. Enrichment of elevated plasma F2t-isoprostane levels in individuals with autism who are stratified by presence of gastrointestinal dysfunction. PLoS One, 8(7), e68444, 2013.

Grelli, KN, Palubinsky, AM, Kale, AC, Lizama-Manibusan, BN, Stankowski, JN, Milne, GL, Singer, R, McLaughlin, B. Alteration of Isocitrate Dehydrogenase Following Acute Ischemic Injury as a Means to Improve Cellular Energetic Status in Neuroadaptation. CNS Neurol Disord Drug Targets, , , 2013.

Ice, RJ, McLaughlin, SL, Livengood, RH, Culp, MV, Eddy, ER, Ivanov, AV, Pugacheva, EN. NEDD9 depletion destabilizes Aurora A kinase and heightens the efficacy of Aurora A inhibitors: implications for treatment of metastatic solid tumors. Cancer Res, 73(10), 3168-80, 2013.

Lizama-Manibusan, B, McLaughlin, B. Redox modification of proteins as essential mediators of CNS autophagy and mitophagy. FEBS Lett, 587(15), 2291-8, 2013.

McLaughlin, B, Gidday, JM. Poised for success: implementation of sound conditioning strategies to promote endogenous protective responses to stroke in patients. Transl Stroke Res, 4(1), 104-13, 2013.

Albers, E, Donahue, BS, Milne, G, Saville, BR, Wang, W, Bichell, D, McLaughlin, B. Perioperative plasma F(2)-isoprostane levels correlate with markers of impaired ventilation in infants with single-ventricle physiology undergoing stage 2 surgical palliation on the cardiopulmonary bypass. Pediatr Cardiol, 33(4), 562-8, 2012.

Kerr, E, Holohan, C, McLaughlin, KM, Majkut, J, Dolan, S, Redmond, K, Riley, J, McLaughlin, K, Stasik, I, Crudden, M, Van Schaeybroeck, S, Fenning, C, O''Connor, R, Kiely, P, Sgobba, M, Haigh, D, Johnston, PG, Longley, DB. Identification of an acetylation-dependant Ku70/FLIP complex that regulates FLIP expression and HDAC inhibitor-induced apoptosis. Cell Death Differ, 19(8), 1317-27, 2012.

McKenzie, JR, Palubinsky, AM, Brown, JE, McLaughlin, B, Cliffel, DE. Metabolic Multianalyte Microphysiometry Reveals Extracellular Acidosis is an Essential Mediator of Neuronal Preconditioning. ACS Chem Neurosci, 3(7), 510-8, 2012.

McLaughlin, B, Buendia, MA, Saborido, TP, Palubinsky, AM, Stankowski, JN, Stanwood, GD. Haploinsufficiency of the E3 ubiquitin ligase C-terminus of heat shock cognate 70 interacting protein (CHIP) produces specific behavioral impairments. PLoS One, 7(5), e36340, 2012. PMCID:3350526

Palubinsky, AM, Martin, JA, McLaughlin, B. The role of central nervous system development in late-onset neurodegenerative disorders. Dev Neurosci, 34(2-3), 129-39, 2012. PMCID:3350526

Brooks, JD, Musiek, ES, Koestner, TR, Stankowski, JN, Howard, JR, Brunoldi, EM, Porta, A, Zanoni, G, Vidari, G, Morrow, JD, Milne, GL, McLaughlin, B. The Fatty Acid Oxidation Product 15-A(3t) -Isoprostane is a Potent Inhibitor Of NFI?B Transcription and Macrophage Transformation. J Neurochem, , , 2011.

Redgrove, KA, Anderson, AL, Dun, MD, McLaughlin, EA, O''Bryan, MK, Aitken, RJ, Nixon, B. Involvement of multimeric protein complexes in mediating the capacitation-dependent binding of human spermatozoa to homologous zonae pellucidae. Dev Biol, 356(2), 460-74, 2011.

Zeiger, SL, Stankowski, JN, McLaughlin, B. Assessing neuronal bioenergetic status. Methods Mol Biol, 758, 215-35, 2011.

Albers, EL, Bichell, DP, McLaughlin, B. New Approaches To Neuroprotection In Infant Heart Surgery. Pediatr Res, (68), , 2010.

Brown, JE, Zeiger, SL, Hettinger, JC, Brooks, JD, Holt, B, Morrow, JD, Musiek, ES, Milne, G, McLaughlin, B. Essential role of the redox-sensitive kinase p66shc in determining energetic and oxidative status and cell fate in neuronal preconditioning. J Neurosci, 30(15), 5242-52, 2010.

Karim, SA, Barrie, JA, McCulloch, MC, Montague, P, Edgar, JM, Iden, DL, Anderson, TJ, Nave, KA, Griffiths, IR, McLaughlin, M. PLP/DM20 expression and turnover in a transgenic mouse model of Pelizaeus-Merzbacher disease. Glia, 58(14), 1727-38, 2010.

Kleman, AM, Brown, JE, Zeiger, SL, Hettinger, JC, Brooks, JD, Holt, B, Morrow, JD, Musiek, ES, Milne, GL, McLaughlin, B. p66(shc)''s role as an essential mitophaghic molecule in controlling neuronal redox and energetic tone. Autophagy, 6(7), 948-9, 2010.

Stankowski, JN, Zeiger, SL, Cohen, EL, Defranco, DB, Cai, J, McLaughlin, BM. C-Terminus of HSC70 Interacting Protein Increases Following Stroke and Impairs Survival Against Acute Oxidative Stress. Antioxid Redox Signal, , , 2010.

Yang, F, Cheng, Y, An, JY, Kwon, YT, Eckardt, S, Leu, NA, McLaughlin, KJ, Wang, PJ. The ubiquitin ligase Ubr2, a recognition E3 component of the N-end rule pathway, stabilizes Tex19.1 during spermatogenesis. PLoS One, 5(11), e14017, 2010.

Zeiger, SL, McKenzie, JR, Stankowski, JN, Martin, JA, Cliffel, DE, McLaughlin, B. Neuron specific metabolic adaptations following multi-day exposures to oxygen glucose deprivation. Biochim Biophys Acta, 1802(11), 1095-104, 2010.

Kawanami, D, Mahabeleshwar, GH, Lin, Z, Atkins, GB, Hamik, A, Haldar, SM, Maemura, K, Lamanna, JC, Jain, MK. Kruppel-like factor 2 inhibits hypoxia-inducible factor 1alpha expression and function in the endothelium. J Biol Chem, 284(31), 20522-30, 2009.

Kazi, A, Lawrence, H, Guida, WC, McLaughlin, ML, Springett, GM, Berndt, N, Yip, RM, Sebti, SM. Discovery of a novel proteasome inhibitor selective for cancer cells over non-transformed cells. Cell Cycle, 8(12), 1940-51, 2009.

Stanwood, GD, Leitch, DB, Savchenko, V, Wu, J, Fitsanakis, VA, Anderson, DJ, Stankowski, JN, Aschner, M, McLaughlin, B. Manganese exposure is cytotoxic and alters dopaminergic and GABAergic neurons within the basal ganglia. J Neurochem, 110(1), 378-89, 2009. PMCID:2737271

Zeiger, SL, Musiek, ES, Zanoni, G, Vidari, G, Morrow, JD, Milne, GJ, McLaughlin, B. Neurotoxic lipid peroxidation species formed by ischemic stroke increase injury. Free Radic Biol Med, 47(10), 1422-1431, 2009.

Cohen, SJ, Engstrom, PF, Lewis, NL, Langer, CJ, McLaughlin, S, Beard, M, Weiner, LM, Meropol, NJ. Phase I study of capecitabine and oxaliplatin in combination with the proteasome inhibitor bortezomib in patients with advanced solid tumors. Am J Clin Oncol, 31(1), 1-5, 2008.

McLaughlin, B.A. and Kirschner, H.. Wagging the dog-moving closer to features defined by basic scientists, the protection of prodromal transient ischaemic attacks reveals itself (p 755-756). European Journal of Neurology, 8(15), 755-756, 2008.

Musiek, ES, Brooks, JD, Joo, M, Brunoldi, E, Porta, A, Zanoni, G, Vidari, G, Blackwell, TS, Montine, TJ, Milne, GL, McLaughlin, B, Morrow, JD. Electrophilic Cyclopentenone Neuroprostanes Are Anti-inflammatory Mediators Formed from the Peroxidation of the {omega}-3 Polyunsaturated Fatty Acid Docosahexaenoic Acid. J Biol Chem, 283(29), 19927-35, 2008. PMCID:2459280

Altay, T, McLaughlin, B, Wu, JY, Park, TS, Gidday, JM. Slit modulates cerebrovascular inflammation and mediates neuroprotection against global cerebral ischemia. Exp Neurol, 207(2), 186-94, 2007. PMCID:2227314

Jiang, GC, Tidwell, K, McLaughlin, BA, Cai, J, Gupta, RC, Milatovic, D, Nass, R, Aschner, M. Neurotoxic potential of depleted uranium effects in primary cortical neuron cultures and in Caenorhabditis elegans. Toxicol Sci, 99(2), 553-65, 2007.

McLaughlin, M, Karim, SA, Montague, P, Barrie, JA, Kirkham, D, Griffiths, IR, Edgar, JM. Genetic background influences UPR but not PLP processing in the rumpshaker model of PMD/SPG2. Neurochem Res, 32(2), 167-76, 2007.

Musiek, ES, McLaughlin, B, Morrow, JD. Electrophilic cyclopentenone isoprostanes in neurodegeneration. J Mol Neurosci, 33(1), 80-6, 2007.

O''Duffy, AE, Bordelon, YM, McLaughlin, B. Killer proteases and little strokes--how the things that do not kill you make you stronger. J Cereb Blood Flow Metab, 27(4), 655-68, 2007.

Hoopfer, ED, McLaughlin, T, Watts, RJ, Schuldiner, O, O''Leary, DD, Luo, L. Wlds protection distinguishes axon degeneration following injury from naturally occurring developmental pruning. Neuron, 50(6), 883-95, 2006.

McLaughlin, M, Barrie, JA, Karim, S, Montague, P, Edgar, JM, Kirkham, D, Thomson, CE, Griffiths, IR. Processing of PLP in a model of Pelizaeus-Merzbacher disease/SPG2 due to the rumpshaker mutation. Glia, 53(7), 715-22, 2006.

Milne, G. L., Musiek, E. S., Zanoni, G., Vidari, G., McLaughlin, B., Morrow, J. D. Development of a novel liquid chromatography-mass spectrometric assay to measure formation of highly reactive cyclopentenone isoprostanes in vivo . Clinical Pharmacology & Therapeutics, 79, 36, 2006.

Musiek, ES, Breeding, RS, Milne, GL, Zanoni, G, Morrow, JD, McLaughlin, B. Cyclopentenone isoprostanes are novel bioactive products of lipid oxidation which enhance neurodegeneration. J Neurochem, 97(5), 1301-13, 2006.

Di Napoli, M, McLaughlin, B. The ubiquitin-proteasome system as a drug target in cerebrovascular disease: therapeutic potential of proteasome inhibitors. Curr Opin Investig Drugs, 6(7), 686-99, 2005.

Goy, A, Younes, A, McLaughlin, P, Pro, B, Romaguera, JE, Hagemeister, F, Fayad, L, Dang, NH, Samaniego, F, Wang, M, Broglio, K, Samuels, B, Gilles, F, Sarris, AH, Hart, S, Trehu, E, Schenkein, D, Cabanillas, F, Rodriguez, AM. Phase II study of proteasome inhibitor bortezomib in relapsed or refractory B-cell non-Hodgkin''s lymphoma. J Clin Oncol, 23(4), 667-75, 2005.

Musiek, ES, Milne, GL, McLaughlin, B, Morrow, JD. Cyclopentenone eicosanoids as mediators of neurodegeneration: a pathogenic mechanism of oxidative stress-mediated and cyclooxygenase-mediated neurotoxicity. Brain Pathol, 15(2), 149-58, 2005.

McLaughlin, B. The kinder side of killer proteases: caspase activation contributes to neuroprotection and CNS remodeling. Apoptosis, 9(2), 111-21, 2004.

McLaughlin, B, Hartnett, KA, Erhardt, JA, Legos, JJ, White, RF, Barone, FC, Aizenman, E. Caspase 3 activation is essential for neuroprotection in preconditioning. Proc Natl Acad Sci U S A, 100(2), 715-20, 2003. PMCID:141062

Tonomura, N, McLaughlin, K, Grimm, L, Goldsby, RA, Osborne, BA. Glucocorticoid-induced apoptosis of thymocytes: requirement of proteasome-dependent mitochondrial activity. J Immunol, 170(5), 2469-78, 2003.

Du, S, McLaughlin, B, Pal, S, Aizenman, E. In vitro neurotoxicity of methylisothiazolinone, a commonly used industrial and household biocide, proceeds via a zinc and extracellular signal-regulated kinase mitogen-activated protein kinase-dependent pathway. J Neurosci, 22(17), 7408-16, 2002.

Legos, JJ, McLaughlin, B, Skaper, SD, Strijbos, PJ, Parsons, AA, Aizenman, E, Herin, GA, Barone, FC, Erhardt, JA. The selective p38 inhibitor SB-239063 protects primary neurons from mild to moderate excitotoxic injury. Eur J Pharmacol, 447(1), 37-42, 2002.

Leszkiewicz, DN, McLaughlin, BA, Aizenman, E. Protein kinases and light: unlikely partners in a receptor localization puzzle. Physiol Behav, 77(4-5), 533-6, 2002.

McLaughlin B.A . Dopamine neurotoxicity and neurodegeneration. In Molecular Mechanisms of Cell Death. Chesselet M.F. ed Humana Press. Totowa, N.J. p. 195-231. Molecular Mechanisms of Cell Death. Chesselet M.F, , 195-231, 2001.

McLaughlin, B, Pal, S, Tran, MP, Parsons, AA, Barone, FC, Erhardt, JA, Aizenman, E. p38 activation is required upstream of potassium current enhancement and caspase cleavage in thiol oxidant-induced neuronal apoptosis. J Neurosci, 21(10), 3303-11, 2001.

Nuttall, ME, Lee, D, McLaughlin, B, Erhardt, JA. Selective inhibitors of apoptotic caspases: implications for novel therapeutic strategies. Drug Discov Today, 6(2), 85-91, 2001.

Aizenman E., Stout A.K., Hartnett K.A., Dineley K.E., McLaughlin B.A., Reynolds I.J. Induction of neuronal apoptosis by thiol oxidation: Putative role of intracellular zinc release. Journal of Neurochemistry., 5(75), 1878-1888, 2000.

Gardner, RC, Assinder, SJ, Christie, G, Mason, GG, Markwell, R, Wadsworth, H, McLaughlin, M, King, R, Chabot-Fletcher, MC, Breton, JJ, Allsop, D, Rivett, AJ. Characterization of peptidyl boronic acid inhibitors of mammalian 20 S and 26 S proteasomes and their inhibition of proteasomes in cultured cells. Biochem J, 346 Pt 2, 447-54, 2000.

Hoyt, KR, McLaughlin, BA, Higgins, DS, Reynolds, IJ. Inhibition of glutamate-induced mitochondrial depolarization by tamoxifen in cultured neurons. J Pharmacol Exp Ther, 293(2), 480-6, 2000. PMCID:2869204

Christie, G, Markwell, RE, Gray, CW, Smith, L, Godfrey, F, Mansfield, F, Wadsworth, H, King, R, McLaughlin, M, Cooper, DG, Ward, RV, Howlett, DR, Hartmann, T, Lichtenthaler, SF, Beyreuther, K, Underwood, J, Gribble, SK, Cappai, R, Masters, CL, Tamaoka, A, Gardner, RL, Rivett, AJ, Karran, EH, Allsop, D. Alzheimer''s disease: correlation of the suppression of beta-amyloid peptide secretion from cultured cells with inhibition of the chymotrypsin-like activity of the proteasome. J Neurochem, 73(1), 195-204, 1999.

McLaughlin B.A. and Levitt P. Molecular basis of neurological disease. Neuroscience Secrets., Hanley & Belfus, Inc., Philadelphia PA.(edited by Wong-Riley M.T.T. ), 349-356, 1999.

McLaughlin, BA, Nelson, D, Ereci??ska, M, Chesselet, MF. Toxicity of dopamine to striatal neurons in vitro and potentiation of cell death by a mitochondrial inhibitor. J Neurochem, 70(6), 2406-15, 1998.

McLaughlin, BA, Nelson, D, Silver, IA, Erecinska, M, Chesselet, MF. Methylmalonate toxicity in primary neuronal cultures. Neuroscience, 86(1), 279-90, 1998.

McLaughlin, BA, Spencer, C, Eberwine, J. CAG trinucleotide RNA repeats interact with RNA-binding proteins. Am J Hum Genet, 59(3), 561-9, 1996. PMCID:1914904

Batshaw, ML, Yudkoff, M, McLaughlin, BA, Gorry, E, Anegawa, NJ, Smith, IA, Hyman, SL, Robinson, MB. The sparse fur mouse as a model for gene therapy in ornithine carbamoyltransferase deficiency. Gene Ther, 2(10), 743-9, 1995.

Eberwine J.H. and McLaughlin B.A. . Striatal RNA-binding proteins interact with huntingtin mRNA. . Molecular and Cellular Mechanisms of Neostriatal Function. , Ariano M.A. and Surmeier D.J. eds, 143-149, 1995.

Robinson, MB, Hopkins, K, Batshaw, ML, McLaughlin, BA, Heyes, MP, Oster-Granite, ML. Evidence of excitotoxicity in the brain of the ornithine carbamoyltransferase deficient sparse fur mouse. Brain Res Dev Brain Res, 90(1-2), 35-44, 1995.


Postdoctoral Position Available
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Postdoctoral Position Details
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Updated Date
04/09/2014



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