Department of Pharmacology & Toxicology

H. Steve White

Professor of Pharmacology and Toxicology

H. Steve WhiteTitle: Professor of Pharmacology and Toxicology
Email address: swhite@hsc.utah.edu

Education and Training:

  • B.S. 1977, Idaho State University
  • M.S. 1979, Idaho State University
  • Ph.D. 1984, University of Utah

Research Interests:

Dr. White is the principal investigator and scientific director of the NIH-sponsored Anticonvulsant Drug Development Program that was established in 1975 to identify novel anticonvulsant drugs using established animal seizure and epilepsy models. Over the years, the efforts of this program have contributed to the successful development of nine new antiepileptic drugs for the treatment of refractory partial epilepsy. Dr. White’s research is focused on understanding the factors which contribute to the initiation, propagation, and amelioration of seizure activity. Dr. White’s laboratory utilizes a variety of in vivo and in vitro model systems to identify and characterize the anticonvulsant profile and potential mechanism of action of established and new antiepileptic drugs. In addition, ongoing investigations in Dr. White’s laboratory are focused on understanding the pathophysiology and genetics of sound-induced seizures in the audiogenic seizure-susceptible Frings mouse and the influence of genetics on seizure-susceptibility and antiepileptic drug pharmacology. In addition to their efforts at identifying new therapies for the symptomatic treatment of partial epilepsy, Dr. White’s laboratory is conducting research that may aid in the identification of disease modifying therapies that halt, slow, or prevent the development of epilepsy in susceptible individuals. Dr. White also participates in a recently funded Drugs of Abuse Program Project Grant as director of a project aimed at identifying the mechanisms that contribute to the proconvulsant properties of methamphetamine and cocaine.

Students working in Dr. White’s laboratory have multiple opportunities to contribute to a broad-based research program aimed at gaining a further understanding of the factors that contribute to the expression and prevention of seizure activity. The results obtained from these investigations are likely to lead to the design and development of more efficacious and less toxic therapies for the prevention and treatment of epilepsy.

Selected Publications:

  • Bialer, M. and White, H.S. Key factors in the discovery and development of new antiepileptic drugs. Nat. Rev. Drug Discov. 9(1):68-82, 2010.
  • Robertson CR, Scholl EA, Pruess TH, Green BR, White HS, Bulaj G. Engineering galanin analogues that discriminate between GalR1 and GalR2 receptor subtypes and exhibit anticonvulsant activity following systemic delivery. J Med Chem, 53(4), 1871-5., 2010.
  • Libbey JE, Kirkman NJ, Wilcox KS, White HS, Fujinami RS. Role for complement in the development of seizures following acute viral infection. J Virol. Jul; 84 (13): 6452-60, Apr 2010.
  • Green BR, White KL, McDougle DR, Zhang L, Klein B, Scholl EA, Pruess TH, White HS, Bulaj G. Introduction of lipidization-cationization motifs affords systemically bioavailable neuropeptide Y and neurotensin analogs with anticonvulsant activities. J Pept Sci, 16(9), 486-95, 2010.
  • Bialer M, Johannessen SI, Levy RH, Perucca E, Tomson T, White HS. (2010). Progress report on new antiepileptic drugs: a summary of the Tenth Eilat Conference (EILAT X). Epilepsy Res, 92(2-3), 89-124.
  • Stewart KA, Wilcox KS, Fujinami RS, White HS. Development of postinfection epilepsy after Theiler's virus infection of C57BL/6 mice. J Neuropathol Exp Neurol, 69(12), 1210-9, 2010.
  • Rowley NM, White HS. Comparative anticonvulsant efficacy in the corneal kindled mouse model of partial epilepsy: Correlation with other seizure and epilepsy models. Epilepsy Res, 92(2-3), 163-9, 2010.
  • Rowley NM, Smith M, Lamb JG, Schousboe A., White Steve H. Hippocampal betaine/GABA transporter mRNA expression is not regulated by inflammation or dehydration post-status eplieticus. Journal of Neurochemistry. 2011 [Epub. Ahead of print].
  • Green BR, Smith M, White KL, White HS, Bulaj G. Analgesic Neuropeptide W Suppresses Seizures in the Brain Revealed by Rationale Repositioning and Peptide Engineering. ACS Chem. Neurosci.:, 2 (1), pp 51-56. DOI:10.1021/cn1000974, 2011.
  • Libbey JE, Kennett NJ, Wilcox KS, White HS, Fujinami RS. Once initiated, viral encephalitis-induced seizures are consistent no matter the treatment or lack of interleukin-6. J Neurovirol. (Epub ahead of print), 2011.
  • Brodie MJ, Covanis A, Gil-Nagel A, Lerche H, Perucca E, Sills GJ, White HS. (2011). Antiepileptic drug therapy: Does mechanism of action matter? Epilepsy Behav, 21(4), 331-41.
  • Libbey JE, Kennett NJ, Wilcox KS, White HS, Fujinami RS. Lack of Correlation of Central Nervous System Inflammation and Neuropathology with the Development of Seizures following Acute Virus Infection. J Virol, 85(16), 8149-57, 2011.
  • Libbey JE, Kennett NJ, Wilcox KS, White HS Fujinami RS. Interleukin-6, produced by resident cells of the central nervous system and infiltrating cells, contributes to the development of seizures following viral infection. J Virol, 85(14), 6913-22, 2011.
  • Madsen KK, Ebert B, Clausen RP, Krogsgaard-Larsen P, Schousboe A, White HS. Selective GABA transporter inhibitors tiagabine and EF1502 exhibit mechanistic differences in their ability to modulate the ataxia and anticonvulsant action of the extrasynaptic GABAA receptor agonist gaboxadol. J Pharmacol Exp Ther, 338(1), 214-9, 2011.
  • Simeone TA, Wilcox KS, White HS. cAMP-Dependent protein kinase A activity modulates topiramate potentiation of GABA(A) receptors. Epilepsy Res. (Epub ahead of print), 2011.
  • Lehre AC, Rowley NM, Zhou Y, Holmseth S, Guo C, Holen T, Hua R, Laake P, Olofsson AM, Poblete-Naredo I, Rusakov DA, Madsen KK, Clausen RP, Schousboe A, White HS, Danbolt NC. Deletion of the betaine-GABA transporter (BGT1; slc6a12) gene does not affect seizure thresholds of adult mice. Epilepsy Res, 95(1-2), 70-81, 2011.
  • Schousboe A, Madsen KK, White HS. GABA transport inhibitors and seizure protection: the past and future. Future Med Chem. 2011 Feb;3(2):183-7. Review. PubMed PMID: 21428813.
  • Robertson CR, Flynn SP, White HS, Bulaj G. Anticonvulsant neuropeptides as drug leads for neurological diseases. Nat Prod Rep. 2011 Apr;28(4):741-62. Epub 2011 Feb 21. Review. PubMed PMID: 21340067.
  • Simeone TA, Wilcox KS, White HS Topiramate modulation of _(1)- and _(3)-homomeric GABA(A) receptors. Pharmacol Res. 2011 Jul;64(1):44-52. Epub 2011 Mar 21. PubMed PMID: 21421049.
  • Libbey JE, Kennett NJ, Wilcox KS, White HS, Fujinami RS. Once initiated, viral encephalitis-induced seizures are consistent no matter the treatment or lack of interleukin-6. J Neurovirol. 2011 Aug 11. [Epub ahead of print] PubMed PMID: 21833798.
  • Sander JWAS, White HS. Disease modification in epilepsy. A Progress in Neurology and Psychiatry Supplement supported by an educational grant from Janssen-Cilag Ltd.
  • White HS, Alex AB, Pollock A, Hen N, Shekh-Ahmad, Wilcox KS, MdDonough JH, Stables JP, Kaufmann D, Yagen B, Bialer M. A new derivative of valproic acid amide possesses a broad-spectrum antiseizure profile and unique activity against status epilepticus and organophospate neuronal damage. Epilepsia. 2012 Jan; 53 (1): 134-46. [PubMed-in process]
  • Large CH, Sokal DM, Nehlig A, Gunthorpe MJ, Sankar R, Crean CS, Vanlandingham KE, White HS. The spectrium of anticonvulsant efficacy of retigabine (exogabine) in animals models: Implications for clinical use. Epilepsia 2012 Jan 5. [Epub ahead of print]
  • Galanopoulou AS, Buckmaster PS, Staley KJ, Moshé SL, Perucca E, Engel J Jr, Löscher W, Noebels JL, Pitkänen A, Stables J, White HS, O'Brien TJ, Simonato M. The American Epilepsy Society Basic Science Committee and the International League Against Epilepsy Working Group on Recommendations for Preclinical Epilepsy Drug Discovery. Identification of new epilepsy treatments: Issues in preclinical methodology. Epilepsia. 2012 Jan 31. [Epub ahead of print]
  • Smeal RM, Stewart KA, Iacob E, Fujinami RS, White HS, Wilcox KS. The activity within the CA3 excitatory network during Theiler's virus encephalitis is distinct from that observed during chronic epilepsy. J Neurovirol. 2012 Feb 11. [Epub ahead of print]
  • Robertson CR, Pruess TH, Grussendorf E, White HS, Bulaj G. Generating orally active galanin analogues with analgesic activities. Chem Med Chem. 2012 May.
  • Platt RJ, Han TS, Green BR, Smith MD, Skalicky J, Gruszczynski P, White HS, Olivera B, Bulaj G, Gajewiak J. Stapling Mimics Noncovalent Interactions of y-Carboxyglutamates in Conantokins, Peptidic Antagonists of N-Methyl-D-Asparatic Acid Receptors. 2012 June 8. J Biol Chem.
  • Gowd KH, Han TS, Twede V, Gajewiak J, Smith MD, Watkins M, Platt RJ, Toledo G, White HS, Olivera BM, Bulaj G. Conantokins Derived from the Asprella Clade Impart conRI-B, an N-Methyl d-Aspartate Receptor Antagonist with a Unique Selectivity Profile for NR2B Subunits. 2012 May 30. Biochemistry.
  • White, H.S. , Franklin, M.R., Kupferberg, H.J., Schmutz, M., Stables, J.P. and Wolf, H.H. The anticonvulsant profile of rufinamide (CG) 33101) in rodent seizure models. Epilepsia, 49(7):1212-1220, 2008.
  • Bulaj, G., Green, B.R., Lee, H.K., Robertson, C.R., White , K., Zjang, L., Sochanska, M., Flynn, S.P., Scholl, E.A., Pruess, T.H., Smith, M.D. and White H.S. Design, synthesis, and characterization of high-affinity, systemically-active galanin analogues with potent anticonvulsant activities. J Med Chem., 51(24):8038-47, 2008.
  • Statler, K.D., Swank, S., Abildskov, T., Bigler, E.D. and White H.S. Traumatic brain injury during development reduces minimal clonic seizure threshold at maturity. Epilepsy Res., 80(2-3):163-70, 2008.
  • 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. Mouse models of human KDNQ2 and KCNQ3 mutations for benign familial neonatal convulsions show seizures and neuronal plasticity without synaptic reorganization. J Physiol., 586(14):3405-23, 2008.
  • Libbey, J.E., Kirkman, N.J., Smith, M.C., Tanaka, T., Wilcox, K.S., White, H.S. and Fujinami, R.S. Seizures following picornavirus infection. Epilepsia, 49(6):1066-74, 2008.
  • Smith, M.D., Saunders, G.W., Clausen, R.P, Frolund, B., Krogsgaard-Larsen, P., Larsson, O.M., Schousboe, A., Wilcox, K.S. and White, H.S. Inhibition of the betaine-GABA transporter (mGAT2/BGT-1) modulates spontaneous electrographic bursting in the medial entorhinal cortex (mEC). Epilepsy Res., 79(1):6-13, 2008.
  • Bulaj, G, Green, BR, Lee, HK, Robertson, CR, White , K, Zhang, L, Sochanska, M, Flynn, SP, Scholl, EA, Pruess, TH, Smith, MD, White, HS. Design, synthesis, and characterization of high-affinity, systemically-active galanin analogues with potent anticonvulsant activities. J Med Chem., 51 (24): 8038-8047, 2008.
  • Bialer, M., Johannessen, S.I., Levy, R.H., Perucca, E., Tomson, T. and White, H.S. Progress report on new antiepileptic drugs: A summary of the Ninth Eilat Conference (EILAT IX). Epilepsy Res., 83(1):1-43, 2009.
  • White, H.S. , Scholl, E.A., Klein, B.D., Flynn, S.P., Pruess, T.H., Green, B.R., Zhang, L., Bulaj, G.. Developing Novel Antiepileptic Drugs: Characterization of NAX 5055, a Systemically-Active Galanin Analog, in Epilepsy Models. The American Society for Experimental NeuroTherapeutics, 2009.
  • Zhang L., Robertson C.R., Green B.R., Pruess T.H., White H.S., Bulaj G. Structural Requirements for a Lipoamino Acid in Modulating the Anticonvulsant Activities of Systemically Active Galanin Analogues. J Med Chem., 2009.
  • Zhang L., Lee H.K., Pruess T.H., White H.S. , Bulaj G. Synthesis and applications of polyamine amino acid residues: improving the bioactivity of an analgesic neuropeptide, neurotensin. J Med Chem., 52 (6): 1514-1517, 2009.
  • Madsen, K.K., Clausen, R.P., Larsson, O.M., Krogsgaard-Larsen, P., Schousboe, A., White, H.S. Synaptic and extrasynaptic GABA transporters as targets for anti-epileptic drugs. J Neurochem., 109:139-144, 2009.
  • Otto JF, Singh NA, Dahle EJ, Leppert MF, Pappas CM, Pruess TH, Wilcox KS, White HS. Electroconvulsive seizure thresholds and kindling acquisition rates are altered in mouse models of human Kcnq2 and Kcnq3 mutations for benign familial neonatal convulsions. Epilepsia. 2009 Apr 27. [Epub ahead of print] PubMed PMID: 19453707.
  • Statler KD, Scheerlinck P, Pouliot W, Hamilton M, , White HS , Dudek FE. A potential model of pediatric posttraumatic epilepsy. Epilepsy Res. 2009 Jun 9. [Epub ahead of print] PubMed PMID: 19520549.
  • Henshall DC, Dürmüller N, White HS , Williams R, Moser P, Dunleavy M, Silverstone PH. Electroencephalographic and behavioral convulsant effects of hydrobromide and hydrochloride salts of bupropion in conscious rodents. Neuropsychiatr Dis Treat. 2009;5:189-206. Epub 2009 Apr 8. PubMed PMID:19557114; PubMed Central PMCID: PMC2695230.
  • Lee HK, Smith MD, Smith BJ, Grussendorf J, Xu L, Gillies RJ, White HS , Bulaj G. Anticonvulsant Met-Enkephalin Analogues Containing Backbone Spacers Reveal Alternative Non-Opioid Signaling in the Brain. ACS Chem Biol. 2009 Jul 27. [Epub ahead of print] PubMed PMID: 19634861.
  • Kirkman Nikki J., Libbey Jane E., Wilcox Karen S., White Steve H., Fujinami Robert S. Innate but Not Adaptive Immune Responses Contribute to Behavioral Seizures Following Viral Infection. Epilepsia, 2009 Oct 20. [Epub ahead of print] 2009.
  • Frankel, W.N., Taylor, L., Beyer, B., Tempel, B.L., and White, H.S. Electroconvulsive thresholds of inbred mouse strains. Genomics, 74(3):306-312, 2001.
  • Skradski, S.L., Clark, A.M., Jiang, H., White, H.S., Fu, Y-H., and Ptacek, L.J. A novel gene causing a Mendelian audiogenic mouse epilepsy. Neuron, 31:537-544, 2001.
  • Isoherranen, N., Woodhead, J.H., White, H.S. and Bialer, M. Anticonvulsant profile of valrocemide (TV1901): A new antiepileptic drug. Epilepsia, 42(7):831-836, 2001.
  • Barton, M.E., Klein, B.D., Wolf, H.H., and White, H.S. Pharmacological characterization of the 6 Hz psychomotor seizure model of partial epilepsy. Epilepsy Res., 47:217-227, 2001.
  • Isoherranen, N., White, H.S., Finnell, R.H., Yagen, B., Woodhead, J.H., Bennett, G.D., Wilcox, K.S., Barton, M.E. and Bialer, M. Anticonvulsant profile and teratogenicity of N-methyl-tetramethylcyclopropyl carboxamide: A new antiepileptic drug. Epilepsia, 43(2):115-126, 2002.
  • Rho, J.M., Anderson, G.D., Donevan, S.D. and White, H.S. Acetoacetate, acetone, and dibenzylamine (a contaminant in 1-(+)-beta-hydroxybutyrate) exhibit direct anticonvulsant actions in vivo. Epilepsia, 43(4):358-361, 2002.
  • Walker, M.C., White, H.S. and Saner, J.W.A.S. Disease modification in partial epilepsy. Brain 2002 (Sept) 129:1937-1950.
  • White, H.S., Sarup A., Bolvig, T., Kristensen, A.S., Petersen, G., Nelson, N., Pickering, D.S., Larsson, O.M., Frolund, B., Krogsgaard-Larsen, P. and Schousboe, A. Corrrelation between Anticonvulsant Activity and Inhibitory Action on Glial gamma-Aminobutyric Acid Uptake of the Highly Selective Mouse gamma-Aminobutyric Acid Transporter 1 Inhibitor 3-Hydroxy-4-amino-4,5,6,7-tetrahydro-1,2-benzisoxazole and Its N-Alkylated Analogs. J Pharmacol Exp Ther. 2002 Aug.;302(2):646-644.