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Karen Wilcox

Professor and Chair of Pharmacology and Toxicology and Adjunct Professor of Biomedical Engineering

Anticonvulsant Drugs, Inflammation, Epilepsy

Karen Wilcox

 

Biological Chemistry Program

Education

B.S. Allegheny College

Ph.D. University of Pennsylvania

 

Research

The Wilcox laboratory is interested in understanding basic mechanisms underlying epileptogenesis, seizure generation, and therapy-resistance to anticonvulsant drugs. To achieve these goals, we use electrophysiological, calcium imaging, pharmacological, behavioral, genetic, immunoblot, and immunohistochemical techniques in a variety of in vitro preparations and animal models of epilepsy. Our working hypothesis is that insight into disease-induced changes in neuronal and glial function will provide new avenues for therapeutic interventions in patients at risk for developing epilepsy or those patients who are refractory to current treatment options. To that end, I am the Principal Investigator of the Anticonvulsant Drug Development (ADD) Program and direct studies determining the anti-seizure potential of proprietary investigational compounds through a contract with NINDS at the National Institutes of Health.

 

wilcox interests

References (Selected Publications)

  1. Remigio GJ, Loewen JL, Heuston S, Helgeson C, White HS, Wilcox KS, West PJ. (2017) “Corneal kindled C57BL/6 mice exhibit saturated dentate gyrus long-term potentiation and associated memory deficits in the absence of overt neuron loss.” Neurobiol Dis 105:221-234.
  2. Smith MD, Woodhead JH, Handy LJ, Pruess TH, Vanegas F, Grussendorf E, Grussendorf J, White K, Bulaj KK, Krumin RK, Hunt M, Wilcox KS. (2017) “Preclinical Comparison of Mechanistically Different Antiseizure, Antinociceptive, and/or Antidepressant Drugs in a Battery of Rodent Models of Nociceptive and Neuropathic Pain.” Neurochem Res 42(7):1995-2010.
  3. Patel DC, Wallis G, Dahle EJ, McElroy PB, Thomson KE, Tesi RJ, Szymkowski DE, West PJ, Smeal RM, Patel M, Fujinami RS, White HS, Wilcox KS. (2017) “Hippocampal TNFα Signaling Contributes to Seizure Generation in an Infection-Induced Mouse Model of Limbic Epilepsy.” eNeuro 4(2). pii: ENEURO.0105-17.2017. 
  4. Klein BD, Jacobson CA, Metcalf CS, Smith MD, Wilcox KS, Hampson AJ, Kehne JH. (2017) “Evaluation of Cannabidiol in Animal Seizure Models by the Epilepsy Therapy Screening Program (ETSP).” Neurochem Res. 42(7):1939-1948.
  5. Metcalf CS, West PJ, Thomson KE, Edwards SF, Smith MD, White HS, Wilcox KS. (2017) “Development and pharmacologic characterization of the rat 6 Hz model of partial seizures.” Epilepsia 58(6):1073-1084.
  6. Barker-Haliski ML, Johnson K, Billingsley P, Huff J, Handy LJ, Khaleel R, Lu Z, Mau MJ, Pruess TH, Rueda C, Saunders G, Underwood TK, Vanegas F, Smith MD, West PJ, Wilcox KS. (2017) “Validation of a Preclinical Drug Screening Platform for Pharmacoresistant Epilepsy.” Neurochem Res 42(7):1904-1918.
  7. Umpierre, A.D., Bennett, I.V., Nebeker, L.D., Newell, T.G., Tian, B.B., Thomson, K.E., White, H.S., White, J.A., and Wilcox, K.S. (2016) “Repeated low-dose kainate administration in C57BL/6J mice produces temporal lobe epilepsy pathology but infrequent spontaneous seizures.” Exp Neurol 279:116-26. PMID: 26896834
  8. Loewen, J.L., Barker-Haliski, M.L., Dahle, E.J., White, H.S., and Wilcox, K.S. (2016) “Neuronal Injury, Gliosis, and Glial Proliferation in Two Models of Temporal Lobe Epilepsy.” J Neuropathol Exp Neurol 75:366-78. PMID: 26945036
  9. Smeal, R.M., Fujinami, R., White, H.S., and Wilcox, K.S. (2015) “Decrease in CA3 inhibitory network activity during Theiler's virus encephalitis.” Neurosci Lett 609:210-5. PMID: 26477780
  10. Bhuyan, P., Patel, D.C., Wilcox, K.S., and Patel, M. (2015) “Oxidative stress in murine Theiler's virus-induced temporal lobe epilepsy.” Exp Neurol 271:329-34. PMID: 26079647
  11. Wilcox, K.S., Gee, J.M., Gibbons, M.B., Tvrdik, P., and White, J.A. (2015) “Altered structure and function of astrocytes following status epilepticus.” Epilepsy Behav 49:17-9. PMID: 26219575
  12. Barker-Haliski, M.L., Dahle, E.J., Heck, T.D., Pruess, T.H., Vanegas, F., Wilcox, K.S., and White, H.S. (2015) “Evaluating an etiologically relevant platform for therapy development for temporal lobe epilepsy: effects of carbamazepine and valproic acid on acute seizures and chronic behavioral comorbidities in the Theiler's murine encephalomyelitis virus mouse model.” J Pharmacol Exp Ther 353:318-29. PMID: 25755209
  13. Gee, J.M., Gibbons, M.B., Taheri, M., Palumbos, S., Morris, S.C., Smeal, R.M., Flynn,  K.F., Economo, M., N., Cizek, C.G., Capecchi, M.R., Tvrdik, P., Wilcox, K.S., and White, J.A. (2015). "Imaging activity in astrocytes and neurons with genetically encoded calcium indicators following in utero electroporation." Front Mol Neurosci 8:10. PMID: 25926768
  14. Umpierre, A.D., Remigio, G.J., Dahle, E.J., Bradford, K., Alex, A.B., Smith, M.D., West, P.J., White, H.S., Wilcox, K.S. (2014) "Impaired cognitive ability and anxiety-like behavior following acute seizures in the Theiler's virus model of temporal lobe epilepsy." Neurobiol Dis 64:98-106.  PMID: 24412221
  15. West, P.J., Saunders, G.W., Remigio, G.J., Wilcox. K.S., White, H.S. (2014) "Antiseizure drugs differentially modulate θ-burst induced long-term potentiation in C57BL/6 mice." Epilepsia 55:214-223. PMID: 24447124
  16. Gee, J.M., Smith, N.A., Fernandez, F.R., Economo, M.N., Brunert, D. Rothermel, M., Morris, S.C., Talbot, A., Palumbos, S., Ichida, J., Shepherd, J.D., West, P.J., Wachowiak, D.M., Capecchi, M.R., Wilcox, K.S., White, J.A., and Tvrdik, P. (2014) "Imaging Activity in Neurons and Glia with a Polr2a-Based and Cre-Dependent GCaMP5G-IRES-tdTomato Reporter Mouse." Neuron 83(5):1058-72. PMID: 25155958
  17. Simonato, M., Brooks-Kayal, A.R., Engel, J. Jr, Galanopoulou, A.S., Jensen, F.E., Moshé, S.L., O'Brien T.J., Pitkanen, A., Wilcox, K.S., French, J.A. (2014) "The challenge and promise of anti-epileptic therapy development in animal models." Lancet Neurol 13(9):949-60.  PMID: 25127174
  18. Gibbons, M.B., Smeal, R.M., Takahashi, D.K., Vargas, J.R., and Wilcox, K.S. (2013) "Contributions of Astrocytes to Epileptogenesis Following Status Epilepticus: Opportunities for Preventive Therapy?" Neurochem International 63(7):660-9. PMID: 23266599
  19. Vargas, J.R., Takahashi, D.K., Thomson, K.E., and Wilcox, K.S. (2013) "The expression of kainate receptor subunits in hippocampal astrocytes following experimentally induced status epilepticus." J Neuropathol Exp Neurol 72(10):919-32.
  20. Wilcox, K.S., Dixon-Salazar, T., Ben-Menachem, E., Porter, R.J., Dichter, M.A.,White, H.S., Noebels, J.L., Privitera, M., and Rogawski, M.A. (2013) "Development of New Anti-Seizure Treatments." Epilepsia 54(Suppl. 4):24–34.
  21. Srivastava, A.K., Alex, A.B., Wilcox, K.S., and White H.S. (2013) "Rapid loss of efficacy to the antiseizure drugs lamotrigine and carbamazepine: A novel experimental model of pharmacoresistant epilepsy." Epilepsia 54(7):1186-94.
  22. Gibbons, M.B., Smeal, R.M., Takahashi, D.K., Vargas, J.R., and Wilcox, K.S. (2013) "Contributions of Astrocytes to Epileptogenesis Following Status Epilepticus: Opportunities for Preventive Therapy?" Neurochem International 63(7):660-9.
  23. Smeal, R. M., Stewart, K. A., Iacob, E., Fujinami, R. S., White, H. S., Wilcox, K. S. (2012) "The activity within the CA3 excitatory network during Theiler's virus encephalitis is distinct from that observed during chronic epilepsy." J Neurovir 18(1):30-44.
  24. Stewart, K.A., Wilcox, K.S., Fujinami, R.S., White, H.S. (2010) "Development of postinfection epilepsy after Theiler's virus infection of C57BL/6 mice." J Neuropathol Exp Neurol 69(12):1210-9.
  25. Takahashi, D.K., Vargas, J.R., Wilcox, K.S. (2010) "Increased coupling and altered glutamate transport currents in astrocytes following kainic-acid-induced status epilepticus." Neurobiol of Dis 40(3):573-85.
  26. Alex, A.B., Saunders, G.W., Dalpe-Charron, A., Reilly, C.A. and Wilcox, K.S. (2011) "Conantokin G protects neurons from excitotoxicity through actions at multiple types of NMDA receptors." Neurotoxicol 32(4):392-9.
  27. Smeal, R. M., Stewart, K. A., Iacob, E., Fujinami, R. S., White, H. S., Wilcox, K. S. (2012) "The activity within the CA3 excitatory network during Theiler's virus encephalitis is distinct from that observed during chronic epilepsy." J Neurovir 18(1):30-44.
  28. Smeal, R.M., Economo, M.N., Lillis, K.P., Wilcox, K.S., White, J.A. (2012) "Targeted path scanning: an emerging method for recording fast changing network dynamics across large distances." J Bioeng & Biom Sci S5:002.
  29. Stewart, K.A., Wilcox, K.S., Fujinami, R.S., and White, H.S. (2010) "Theiler’s virus infection chronically alters seizure susceptibility." Epilepsia 51(8):1418-28.
  30. Otto, J.F, Singh, N.A., Leppert, M.F., Dahle, E.J., Pappas, C., Pruess, T., Wilcox, K.S., and White, H.S. (2009) "Electroconvulsive Seizure Thresholds and Kindling Acquisition Rates Are Altered in Mouse Models of Human KCNQ2 and KCNQ3 Mutations for Benign Familial Neonatal Convulsions." Epilepsia 50(7):1752-1759.
  31. Smeal, R. M., Keefe, K.A., and Wilcox, K.S. (2008) "Differences in excitatory transmission between thalamic and cortical afferents to single spiny efferent neurons of dorsal striatum." Eur J Neurosci 28(10):2041-52.
  32. Singh, N. A., Otto, J.F, Dahle, E.J., Pappas, C., Leslie, J.D., Vilaythong, A., Noebels, J.L., White, H.S.,Wilcox, K. S. , and Leppert, M. F. (2008) "Neuronal Plasticity Without Synaptic Reorganization in Kcnq2 and Kcnq3 Mouse Models of Benign Familial Neonatal Convulsions." J Physiol 586(14):3405-23.
  33. White, H.S., Smith, M.D., and Wilcox, K.S. (2007) "Mechanisms of action of antiepileptic drugs." Int Rev Neurobiol 81:85-110.
  34. West, P.J., Dalpe-Charron, A., and Wilcox, K.S. (2007) "Differential Contribution of Kainate Receptors to Excitatory Postsynaptic Currents in Superficial Layer Neurons of the Rat Medial Entorhinal Cortex." Neuroscience 146(3):1000-12.
  35. Smith, M.D., Adams, A.C., Saunders, G.W., White, H.S., and Wilcox, K.S. (2007) "Phenytoin- and Carbamazepine-Resistant Spontaneous Bursting in Rat Entorhinal Cortex Is Blocked by Retigabine In Vitro." Epilepsy Res 74 (2-3):97-106.
  36. Smith, M.D., Wilcox, K.S., and White, H.S. (2007) "Discovery of Antiepileptic Drugs." Neurotherapeutics 4(1):12-7.
  37. Smeal, R. M., Gaspar, R., Keefe, K.A., and Wilcox, K.S (2007) "A rat brain slice preparation for characterizing both thalamostriatal and corticostriatal afferents." J Neurosci Methods 159(2):224-35.
  38. Simeone, T.A., Otto, J.F., Wilcox, K.S., and White, H.S. (2006) "Felbamate is a subunit selective modulator of recombinant gamma-aminobutyric acid type A receptors expressed in Xenopus oocytes." Eur J Pharmacol 552:31-35.
  39. Alex A.B., Baucum A.J., and Wilcox, K.S. (2006) "Effect of Conantokin G on NMDA receptor-mediated spontaneous EPSCs in cultured cortical neurons." J Neurophysiol 96:1084-1092.
  40. Simeone, T.A., Wilcox, K.S., and White, H.S. (2006) "Subunit selectivity of topiramate modulation of heteromeric GABAA receptors." Neuropharmacology 50(7):845-57.
  41. Otto, J.F., Yang, Y., Frankel, W.N., White, H.S. and Wilcox, K.S. (2006) "A Spontaneous Mutation Involving Kcnq2 (Kv7.2) Reduces M Current Density and Spike Frequency Adaptation in Mouse CA1 Neurons." J Neurosci 26(7):2053-9.
Last Updated: 7/30/21