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Last Name
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Kent Vrana

TitleProfessor
InstitutionCollege of Medicine
DepartmentPharmacology
Address500 University Drive Hershey PA 17033
Mailbox: R130
Phone7175318285

 Overview 
 overview
Title/Institutional Role(s):

Elliot S. Vesell Professor and Chair of Pharmacology

Co-Leader, Unified Campus Research Team

Co-Director, Clinical Learning and Competencies (Problem-Based Learning, PBL)

Member, Society of Distinguished Educators



Educational Background:

B.S. (Biochemistry), University of Iowa (1978)

Ph.D. (Biochemistry), Louisiana State University Health Sciences Center (1983)

NIH Postdoctoral Fellow (Embryology and Molecular Biology), Carnegie Institution of Wahington (1986)



Narrative:

The central theme of the research in this laboratory involves the use of molecular biology and proteomics to study the nervous system. Specifically, the laboratory is actively engaged in: (a) understanding structure/ function relationships in the biogenic amine (dopamine, norepinephrine, epinephrine, and serotonin) biosynthetic enzymes (tyrosine hydroxylase and tryptophan hydroxylase); (b) using functional genomic (DNA array, RT-PCR) and proteomic (2-D PAGE, mass spectrometry) technologies to better understand genomic and epigenetic factors in substance abuse (cocaine, heroin, and alcohol) and neurodegeneration; and (c) stem cell development and characterization.



The rate-limiting enzyme in catecholamine biosynthesis is tyrosine hydroxylase (TH), while the rate-limiting enzyme in serotonin biosynthesis is tryptophan hydroxylase (TPH). In one aspect of our work, full-length cDNA clones for TH and TPH are modified by site-directed mutagenesis and the mutant proteins expressed in bacteria. The recombinant enzymes are then characterized in terms of their structure, activity and regulation. The results of these studies provide insights into how these pivotal enzymes function in health and disease (including the functional consequences of human single nucleotide polymorphisms). A central premise of our second research area is that chronic drug abuse creates an epigenetic imprint – a stable environmental alteration in the pattern of mRNA and protein expression – that contributes to such clinical observations as physical dependence, psychological addiction, withdrawal, and relapse liability. While this laboratory has characterized environmental effects on gene expression for many years, we have more recently adopted high throughput methods (multiplex DNA microarrays and mass spectrometry) to identify those mRNAs and proteins that are engaged in the polygenic problem of substance abuse. In a third, more recent aspect of our work, new efforts within the laboratory have focused on the study of human embryonic and adult stem cells, as well as induced pluripotent stem cells. We were part of the research team that demonstrated the ability to generate pluripotent embryonic stem cells via parthenogenetic activation of oocytes in non-human primates. This ability to create ES cells from non-fertilized, self-limiting, and non-viable embryos may provide ethical alternatives to the use of fertilized embryos in therapeutic cloning applications. Proteomic and functional genomic tools are being used to profile those genes and gene products that contribute to “stemness”, as well as stem cell differentiation.




 Bibliographic 
 selected publications
Publications listed below are automatically derived from MEDLINE/PubMed and other sources, which might result in incorrect or missing publications. Faculty can login to make corrections and additions.
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  1. Vrana KE. "Making it real" time. Biotechniques. 2013 Jun; 54(6):312-3.
    View in: PubMed
  2. Karpa KD, Vrana KE. Creating a virtual pharmacology curriculum in a problem-based learning environment: one medical school's experience. Acad Med. 2013 Feb; 88(2):198-205.
    View in: PubMed
  3. Dowhower Karpa K, Paul IM, Leckie JA, Shung S, Carkaci-Salli N, Vrana KE, Mauger D, Fausnight T, Poger J. A retrospective chart review to identify perinatal factors associated with food allergies. Nutr J. 2012; 11:87.
    View in: PubMed
  4. Torrente MP, Freeman WM, Vrana KE. Protein biomarkers of alcohol abuse. Expert Rev Proteomics. 2012 Aug; 9(4):425-36.
    View in: PubMed
  5. Huber-Keener KJ, Liu X, Wang Z, Wang Y, Freeman W, Wu S, Planas-Silva MD, Ren X, Cheng Y, Zhang Y, Vrana K, Liu CG, Yang JM, Wu R. Differential gene expression in tamoxifen-resistant breast cancer cells revealed by a new analytical model of RNA-Seq data. PLoS One. 2012; 7(7):e41333.
    View in: PubMed
  6. Carkaci-Salli N, Battula S, Wang X, Connor JR, Vrana KE. Gender-specific regulation of tyrosine hydroxylase in thymocyte differentiation antigen-1 knockout mice. J Neurosci Res. 2012 Aug; 90(8):1583-8.
    View in: PubMed
  7. Kester M, Vrana K, Karpa K. Integrated Pharmacology, Second Edition; Elsevier-Saunders, Philadelphia. 2012; 243 pp.
  8. Torrente MP, Gelenberg AJ, Vrana KE. Boosting serotonin in the brain: is it time to revamp the treatment of depression? J Psychopharmacol. 2012 May; 26(5):629-35.
    View in: PubMed
  9. Helms CM, Messaoudi I, Jeng S, Freeman WM, Vrana KE, Grant KA. A longitudinal analysis of circulating stress-related proteins and chronic ethanol self-administration in cynomolgus macaques. Alcohol Clin Exp Res. 2012 Jun; 36(6):995-1003.
    View in: PubMed
  10. Freeman WM, Vanguilder HD, Guidone E, Krystal JH, Grant KA, Vrana KE. Plasma proteomic alterations in non-human primates and humans after chronic alcohol self-administration. Int J Neuropsychopharmacol. 2011 Aug; 14(7):899-911.
    View in: PubMed
  11. Carkaci-Salli N, Salli U, Kuntz-Melcavage KL, Pennock MM, Ozgen H, Tekin I, Freeman WM, Vrana KE. TPH2 in the ventral tegmental area of the male rat brain. Brain Res Bull. 2011 Apr 5; 84(6):376-80.
    View in: PubMed
  12. Plazas-Mayorca MD, Vrana KE. Proteomic investigation of epigenetics in neuropsychiatric disorders: a missing link between genetics and behavior? J Proteome Res. 2011 Jan 7; 10(1):58-65.
    View in: PubMed
  13. Umstead TM, Lu CJ, Freeman WM, Myers JL, Clark JB, Thomas NJ, Chinchilli VM, Vrana KE, Undar A, Phelps DS. Dual-platform proteomics study of plasma biomarkers in pediatric patients undergoing cardiopulmonary bypass. Pediatr Res. 2010 Jun; 67(6):641-9.
    View in: PubMed
  14. Freeman WM, Vrana KE. Future prospects for biomarkers of alcohol consumption and alcohol-induced disorders. Alcohol Clin Exp Res. 2010 Jun; 34(6):946-54.
    View in: PubMed
  15. Mathew R, Jia W, Sharma A, Zhao Y, Clarke LE, Cheng X, Wang H, Salli U, Vrana KE, Robertson GP, Zhu J, Wang S. Robust activation of the human but not mouse telomerase gene during the induction of pluripotency. FASEB J. 2010 Aug; 24(8):2702-15.
    View in: PubMed
  16. Freeman WM, Salzberg AC, Gonzales SW, Grant KA, Vrana KE. Classification of alcohol abuse by plasma protein biomarkers. Biol Psychiatry. 2010 Aug 1; 68(3):219-22.
    View in: PubMed
  17. Freeman WM, Lull ME, Patel KM, Brucklacher RM, Morgan D, Roberts DC, Vrana KE. Gene expression changes in the medial prefrontal cortex and nucleus accumbens following abstinence from cocaine self-administration. BMC Neurosci. 2010; 11:29.
    View in: PubMed
  18. Gohlke JM, Freeman WM, Vrana KE. Neurotoxicology, Tilson H and Harry, J (eds.). Bioinformatic and Computational Approaches for Analysis of Genomics Data in Neurotoxicology Research. 2010; 29-49.
  19. Mailman RB, Vrana KE. Burger’s Medicinal Chemistry, Drug Discovery and Development, Abraham DJ and Rotella DP (eds.). Chemical Perspective on Neurotransmission and Drug Discovery. 2010.
  20. Achur RN, Freeman WM, Vrana KE. Circulating cytokines as biomarkers of alcohol abuse and alcoholism. J Neuroimmune Pharmacol. 2010 Mar; 5(1):83-91.
    View in: PubMed
  21. Lull ME, Freeman WM, VanGuilder HD, Vrana KE. The use of neuroproteomics in drug abuse research. Drug Alcohol Depend. 2010 Feb 1; 107(1):11-22.
    View in: PubMed
  22. Undar A, Pauliks L, Clark JB, Zahn J, Rosenberg G, Kunselman AR, Sun Q, Pekkan K, Saliba K, Carney E, Thomas N, Freeman W, Vrana K, El-Banayosy A, Ural SH, Wilson R, Umstead TM, Floros J, Phelps DS, Weiss W, Snyder A, Yang S, Kimatian S, Cyran SE, Chinchilli VM, Guan Y, Rider A, Haines N, Rogerson A, Alkan-Bozkaya T, Akcevin A, Sun K, Wang S, Cun L, Myers JL. Penn State Hershey--center for pediatric cardiovascular research. Artif Organs. 2009 Nov; 33(11):883-7.
    View in: PubMed
  23. Lei F, Haque R, Weiler L, Vrana KE, Song J. T lineage differentiation from induced pluripotent stem cells. Cell Immunol. 2009; 260(1):1-5.
    View in: PubMed
  24. Kuntz-Melcavage KL, Brucklacher RM, Grigson PS, Freeman WM, Vrana KE. Gene expression changes following extinction testing in a heroin behavioral incubation model. BMC Neurosci. 2009; 10:95.
    View in: PubMed
  25. Desai D, Salli U, Vrana KE, Amin S. SelSA, selenium analogs of SAHA as potent histone deacetylase inhibitors. Bioorg Med Chem Lett. 2010 Mar 15; 20(6):2044-7.
    View in: PubMed
  26. Jaishankar A, Barthelery M, Freeman WM, Salli U, Ritty TM, Vrana KE. Human embryonic and mesenchymal stem cells express different nuclear proteomes. Stem Cells Dev. 2009 Jun; 18(5):793-802.
    View in: PubMed
  27. Jaishankar A, Vrana K. Emerging molecular approaches in stem cell biology. Biotechniques. 2009 Apr; 46(5):367-71.
    View in: PubMed
  28. Barthéléry M, Jaishankar A, Salli U, Freeman WM, Vrana KE. 2-D DIGE identification of differentially expressed heterogeneous nuclear ribonucleoproteins and transcription factors during neural differentiation of human embryonic stem cells. Proteomics Clin Appl. 2009 Apr; 3(4):505-14.
    View in: PubMed
  29. Lull ME, Erwin MS, Morgan D, Roberts DC, Vrana KE, Freeman WM. Persistent proteomic alterations in the medial prefrontal cortex with abstinence from cocaine self-administration. Proteomics Clin Appl. 2009 Mar 17; 3(4):462-472.
    View in: PubMed
  30. Barthéléry M, Jaishankar A, Salli U, Vrana KE. Reptin52 expression during in vitro neural differentiation of human embryonic stem cells. Neurosci Lett. 2009 Mar 6; 452(1):47-51.
    View in: PubMed
  31. Miller A, Lu CK, Wang S, Umstead TM, Freeman WM, Vrana K, Yang S, Myers JL, Phelps DS, Zahn JD, Undar A. Pediatric cardiopulmonary bypass circuits: a review of studies conducted at the Penn State Pediatric Cardiac Research Laboratories. J Extra Corpor Technol. 2009 Mar; 41(1):P50-8.
    View in: PubMed
  32. Salli U, Fox TE, Carkaci-Salli N, Sharma A, Robertson GP, Kester M, Vrana KE. Propagation of undifferentiated human embryonic stem cells with nano-liposomal ceramide. Stem Cells Dev. 2009 Jan-Feb; 18(1):55-65.
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  33. Lull ME, Freeman WM, Vrana KE, Mash DC. Correlating human and animal studies of cocaine abuse and gene expression. Ann N Y Acad Sci. 2008 Oct; 1141:58-75.
    View in: PubMed
  34. Lull ME, Carkaci-Salli N, Freeman WM, Myers JL, Midgley FM, Thomas NJ, Kimatian SJ, Vrana KE, Undar A. Plasma biomarkers in pediatric patients undergoing cardiopulmonary bypass. Pediatr Res. 2008 Jun; 63(6):638-44.
    View in: PubMed
  35. Barthéléry M, Salli U, Vrana KE. Enhanced nuclear proteomics. Proteomics. 2008 May; 8(9):1832-8.
    View in: PubMed
  36. Kuntz KL, Twining RC, Baldwin AE, Vrana KE, Grigson PS. Heroin self-administration: I. Incubation of goal-directed behavior in rats. Pharmacol Biochem Behav. 2008 Sep; 90(3):344-8.
    View in: PubMed
  37. Kuntz KL, Patel KM, Grigson PS, Freeman WM, Vrana KE. Heroin self-administration: II. CNS gene expression following withdrawal and cue-induced drug-seeking behavior. Pharmacol Biochem Behav. 2008 Sep; 90(3):349-56.
    View in: PubMed
  38. VanGuilder HD, Vrana KE, Freeman WM. Twenty-five years of quantitative PCR for gene expression analysis. Biotechniques. 2008 Apr; 44(5):619-26.
    View in: PubMed
  39. Barthelery M, Salli U, Vrana KE. Nuclear proteomics and directed differentiation of embryonic stem cells. Stem Cells Dev. 2007 Dec; 16(6):905-19.
    View in: PubMed
  40. Freeman WM, Patel KM, Brucklacher RM, Lull ME, Erwin M, Morgan D, Roberts DC, Vrana KE. Persistent alterations in mesolimbic gene expression with abstinence from cocaine self-administration. Neuropsychopharmacology. 2008 Jul; 33(8):1807-17.
    View in: PubMed
  41. Ward GR, Franklin SO, Gerald TM, Dempsey KT, Clodfelter DE, Krissinger DJ, Patel KM, Vrana KE, Howlett AC. Glucocorticoids plus opioids up-regulate genes that influence neuronal function. Cell Mol Neurobiol. 2007 Aug; 27(5):651-60.
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  42. Jones JD, Carney ST, Vrana KE, Norford DC, Howlett AC. Cannabinoid receptor-mediated translocation of NO-sensitive guanylyl cyclase and production of cyclic GMP in neuronal cells. Neuropharmacology. 2008 Jan; 54(1):23-30.
    View in: PubMed
  43. Fitzpatrick LR, Hertzog KL, Quatse AL, Koltun WA, Small JS, Vrana K. Effects of the probiotic formulation VSL#3 on colitis in weanling rats. J Pediatr Gastroenterol Nutr. 2007 May; 44(5):561-70.
    View in: PubMed
  44. Salli U, Long SW, Carlsen WS, Vrana KE. Stem cell biology should be taught in high schools. CBE Life Sci Educ. 2007; 6(4):283-4.
    View in: PubMed
  45. Kester M, Vrana K, Quraishi S, Karpa K. Integrated Pharmacology. 2007; 235 pp..
  46. Bowyer JF, Pogge AR, Delongchamp RR, O'Callaghan JP, Patel KM, Vrana KE, Freeman WM. A threshold neurotoxic amphetamine exposure inhibits parietal cortex expression of synaptic plasticity-related genes. Neuroscience. 2007 Jan 5; 144(1):66-76.
    View in: PubMed
  47. Lull ME, Freeman WM, Myers JL, Midgley F, Kimatian SJ, Undar A, Vrana KE. Plasma proteomics: a noninvasive window on pathology and pediatric cardiac surgery. ASAIO J. 2006 Sep-Oct; 52(5):562-6.
    View in: PubMed
  48. Carkaci-Salli N, Flanagan JM, Martz MK, Salli U, Walther DJ, Bader M, Vrana KE. Functional domains of human tryptophan hydroxylase 2 (hTPH2). J Biol Chem. 2006 Sep 22; 281(38):28105-12.
    View in: PubMed
  49. Freeman WM, Lull ME, Guilford MT, Vrana KE. Depletion of abundant proteins from non-human primate serum for biomarker studies. Proteomics. 2006 May; 6(10):3109-13.
    View in: PubMed
  50. Freeman WM, Gooch RS, Lull ME, Worst TJ, Walker SJ, Xu AS, Green H, Pierre PJ, Grant KA, Vrana KE. Apo-AII is an elevated biomarker of chronic non-human primate ethanol self-administration. Alcohol Alcohol. 2006 May-Jun; 41(3):300-5.
    View in: PubMed
  51. Cibelli JB, Cunniff K, Vrana KE. Embryonic stem cells from parthenotes. Methods Enzymol. 2006; 418:117-35.
    View in: PubMed
  52. McCracken CB, Hamby SM, Patel KM, Morgan D, Vrana KE, Roberts DC. Extended cocaine self-administration and deprivation produces region-specific and time-dependent changes in connexin36 expression in rat brain. Synapse. 2005 Dec 1; 58(3):141-50.
    View in: PubMed
  53. Worst TJ, Tan JC, Robertson DJ, Freeman WM, Hyytia P, Kiianmaa K, Vrana KE. Transcriptome analysis of frontal cortex in alcohol-preferring and nonpreferring rats. J Neurosci Res. 2005 May 15; 80(4):529-38.
    View in: PubMed
  54. McCracken CB, Patel KM, Vrana KE, Paul DL, Roberts DC. Amphetamine withdrawal produces region-specific and time-dependent changes in connexin36 expression in rat brain. Synapse. 2005 Apr; 56(1):39-44.
    View in: PubMed
  55. Freeman WM, Vrana KE. Cell Biology of Addiction. Quantitative Functional Genomics and Proteomics of Drug Abuse. 2005; 433-56.
  56. Hipp JD, Mychaleckyj JC, Cibelli JB, Wininger JD, Grant KA, Vrana KE. Encyclopedia of Molecular Cell Biology and Molecular Medicine. Parthenogenic Stem Cells. 2005; 10:71-85.
  57. Worst TJ, Vrana KE. Alcohol and gene expression in the central nervous system. Alcohol Alcohol. 2005 Jan-Feb; 40(1):63-75.
    View in: PubMed
  58. Stredrick DL, Stokes AH, Worst TJ, Freeman WM, Johnson EA, Lash LH, Aschner M, Vrana KE. Manganese-induced cytotoxicity in dopamine-producing cells. Neurotoxicology. 2004 Jun; 25(4):543-53.
    View in: PubMed
  59. Kasinathan C, Vrana K, Beretta L, Thomas P, Gooch R, Worst T, Walker S, Xu A, Pierre P, Green H, Grant K, Manowitz P. The future of proteomics in the study of alcoholism. Alcohol Clin Exp Res. 2004 Feb; 28(2):228-32.
    View in: PubMed
  60. Gooch RS, Worst TJ, Freeman WM, Vrana KE. Comprehensive Handbook of Alcohol Related Pathology. cDNA arrays in alcohol-related pathology: Methods and Approaches. 2004; 3:1597-1611.
  61. Walker SJ, Worst TJ, Freeman WM, Vrana KE. Functional genomic analysis in pain research using hybridization arrays. Methods Mol Med. 2004; 99:239-53.
    View in: PubMed
  62. Yohrling GJ, Jiang GC, DeJohn MM, Miller DW, Young AB, Vrana KE, Cha JH. Analysis of cellular, transgenic and human models of Huntington's disease reveals tyrosine hydroxylase alterations and substantia nigra neuropathology. Brain Res Mol Brain Res. 2003 Nov 6; 119(1):28-36.
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  63. Vrana KE, Hipp JD, Goss AM, McCool BA, Riddle DR, Walker SJ, Wettstein PJ, Studer LP, Tabar V, Cunniff K, Chapman K, Vilner L, West MD, Grant KA, Cibelli JB. Nonhuman primate parthenogenetic stem cells. Proc Natl Acad Sci U S A. 2003 Sep 30; 100 Suppl 1:11911-6.
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  64. Vrana KE, Freeman WM, Aschner M. Use of microarray technologies in toxicology research. Neurotoxicology. 2003 Jun; 24(3):321-32.
    View in: PubMed
  65. Patel VB, Chaurand P, Caprioli RM, Austen BM, Frears ER, Manca F, Davies H, Vrana KE, Wheeler M, Preedy VR. Emerging techniques in biomedical research and their application to alcohol toxicity. Alcohol Clin Exp Res. 2003 Feb; 27(2):348-53.
    View in: PubMed
  66. Worst TJ, Freeman WM, Walker SJ, Vrana KE. Systematic screening of gene expression using a cDNA macroarray. Methods Mol Med. 2003; 79:243-59.
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  67. Walker SJ, Worst TJ, Vrana KE. Semiquantitative real-time PCR for analysis of mRNA levels. Methods Mol Med. 2003; 79:211-27.
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  68. Stokes AH, Freeman WM, Mitchell SG, Burnette TA, Hellmann GM, Vrana KE. Induction of GADD45 and GADD153 in neuroblastoma cells by dopamine-induced toxicity. Neurotoxicology. 2002 Dec; 23(6):675-84.
    View in: PubMed
  69. Freeman WM, Brebner K, Patel KM, Lynch WJ, Roberts DC, Vrana KE. Repeated cocaine self-administration causes multiple changes in rat frontal cortex gene expression. Neurochem Res. 2002 Oct; 27(10):1181-92.
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  70. Yohrling IV GJ, Jiang GC, DeJohn MM, Robertson DJ, Vrana KE, Cha JH. Inhibition of tryptophan hydroxylase activity and decreased 5-HT1A receptor binding in a mouse model of Huntington's disease. J Neurochem. 2002 Sep; 82(6):1416-23.
    View in: PubMed
  71. Freeman WM, Brebner K, Lynch WJ, Patel KM, Robertson DJ, Roberts DC, Vrana KE. Changes in rat frontal cortex gene expression following chronic cocaine. Brain Res Mol Brain Res. 2002 Jul 15; 104(1):11-20.
    View in: PubMed
  72. Weber S, Dorman DC, Lash LH, Erikson K, Vrana KE, Aschner M. Effects of manganese (Mn) on the developing rat brain: oxidative-stress related endpoints. Neurotoxicology. 2002 Jul; 23(2):169-75.
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  73. Haycock JW, Kumer SC, Lewis DA, Vrana KE, Stockmeier CA. A monoclonal antibody to tryptophan hydroxylase: applications and identification of the epitope. J Neurosci Methods. 2002 Mar 15; 114(2):205-12.
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  74. Freeman WM, Dougherty KE, Vacca SE, Vrana KE. An interactive database of cocaine-responsive gene expression. ScientificWorldJournal. 2002 Mar 12; 2:701-6.
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  75. Cibelli JB, Grant KA, Chapman KB, Cunniff K, Worst T, Green HL, Walker SJ, Gutin PH, Vilner L, Tabar V, Dominko T, Kane J, Wettstein PJ, Lanza RP, Studer L, Vrana KE, West MD. Parthenogenetic stem cells in nonhuman primates. Science. 2002 Feb 1; 295(5556):819.
    View in: PubMed
  76. Beckstead MJ, Lopreato GF, Vrana KE, Mihic SJ. Methods in Alcohol-Related Neuroscience Research (Y Liu and DM Lovinger, eds.). Molecular Studies by Chimeragenesis and Mutagenesis. 2002; 63-81.
  77. Freeman WM, Vrana KE. DNA Hybridization Arrays (EV Grigorenko, ed.). Experimental Design for Hybridization Array Analysis of Gene Expression. 2002; 11-24.
  78. Blanchard-Fillion B, Souza JM, Friel T, Jiang GC, Vrana K, Sharov V, Barrón L, Schöneich C, Quijano C, Alvarez B, Radi R, Przedborski S, Fernando GS, Horwitz J, Ischiropoulos H. Nitration and inactivation of tyrosine hydroxylase by peroxynitrite. J Biol Chem. 2001 Dec 7; 276(49):46017-23.
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  79. Walker SJ, Grant KA, Vrana KE. Examination of a CYP2E1 repeat polymorphism in a monkey model of alcohol abuse. Alcohol Clin Exp Res. 2001 Aug; 25(8):1114-8.
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  80. Freeman WM, Nader MA, Nader SH, Robertson DJ, Gioia L, Mitchell SM, Daunais JB, Porrino LJ, Friedman DP, Vrana KE. Chronic cocaine-mediated changes in non-human primate nucleus accumbens gene expression. J Neurochem. 2001 Apr; 77(2):542-9.
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  81. Freeman WM, Brebner K, Lynch WJ, Robertson DJ, Roberts DC, Vrana KE. Cocaine-responsive gene expression changes in rat hippocampus. Neuroscience. 2001; 108(3):371-80.
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  82. Walker SJ, Howard TD, Hawkins GA, Lockwood D, Branca M, Vrana KE. Cambridge Healthtech Institute’s Genomic Reports Series. High Throughput Genomics: Maximizing Efficiency and Productivity for Drug Discovery and Development. 2001; 182 pp..
  83. Vrana KE, Freeman WM, Vaccaro D, Castrodale B. Cambridge Healthtech Institute’s Genomic Pathways Reports Series. DNA Microarrays and Related Technologies: Miniaturization and Acceleration of Genomic Research. 2001; 152 pp..
  84. Freeman WM, Yohrling GJ, Daunais JB, Gioia L, Hart SL, Porrino LJ, Davies HM, Vrana KE. A cocaine analog, 2beta-propanoyl-3beta-(4-tolyl)-tropane (PTT), reduces tyrosine hydroxylase in the mesolimbic dopamine pathway. Drug Alcohol Depend. 2000 Dec 22; 61(1):15-21.
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  85. Freeman WM, Robertson DJ, Vrana KE. Fundamentals of DNA hybridization arrays for gene expression analysis. Biotechniques. 2000 Nov; 29(5):1042-6, 1048-55.
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  86. Jiang GC, Yohrling GJ, Schmitt JD, Vrana KE, Yohrling GJ, Schmitt IV. Identification of substrate orienting and phosphorylation sites within tryptophan hydroxylase using homology-based molecular modeling. J Mol Biol. 2000 Sep 29; 302(4):1005-17.
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  87. Yohrling GJ, Jiang GC, Mockus SM, Vrana KE. Intersubunit binding domains within tyrosine hydroxylase and tryptophan hydroxylase. J Neurosci Res. 2000 Aug 1; 61(3):313-20.
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  88. Stokes AH, Xu Y, Daunais JA, Tamir H, Gershon MD, Butkerait P, Kayser B, Altman J, Beck W, Vrana KE. p-ethynylphenylalanine: a potent inhibitor of tryptophan hydroxylase. J Neurochem. 2000 May; 74(5):2067-73.
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  89. Stokes AH, Lewis DY, Lash LH, Jerome WG, Grant KW, Aschner M, Vrana KE. Dopamine toxicity in neuroblastoma cells: role of glutathione depletion by L-BSO and apoptosis. Brain Res. 2000 Mar 6; 858(1):1-8.
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  90. Freeman WM, Vrana KE. Cambridge Healthtech Institute’s Genomic Pathways Reports Series. Genomic-Scale Gene Expression Analysis: Advancing from DNA to Disease. 2000; 116 pp.
  91. Letchworth SR, Sexton T, Childers SR, Vrana KE, Vaughan RA, Davies HM, Porrino LJ. Regulation of rat dopamine transporter mRNA and protein by chronic cocaine administration. J Neurochem. 1999 Nov; 73(5):1982-9.
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  92. Vrana KE. How the regulatory and catalytic domains get together. Nat Struct Biol. 1999 May; 6(5):401-2.
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  93. Aschner M, Vrana KE, Zheng W. Manganese uptake and distribution in the central nervous system (CNS). Neurotoxicology. 1999 Apr-Jun; 20(2-3):173-80.
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  94. Stokes AH, Hastings TG, Vrana KE. Cytotoxic and genotoxic potential of dopamine. J Neurosci Res. 1999 Mar 15; 55(6):659-65.
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  95. Yohrling GJ, Mockus SM, Vrana KE. Identification of amino-terminal sequences contributing to tryptophan hydroxylase tetramer formation. J Mol Neurosci. 1999 Feb; 12(1):23-34.
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  96. Freeman WM, Walker SJ, Vrana KE. Quantitative RT-PCR: pitfalls and potential. Biotechniques. 1999 Jan; 26(1):112-22, 124-5.
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  97. Vrana KE. Rypins’ Intensive Reviews: Biochemistry. 1999; 283 pp.
  98. Xu Y, Stokes AH, Roskoski R, Vrana KE. Dopamine, in the presence of tyrosinase, covalently modifies and inactivates tyrosine hydroxylase. J Neurosci Res. 1998 Dec 1; 54(5):691-7.
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  99. Vogt BA, Vogt LJ, Vrana KE, Gioia L, Meadows RS, Challa VR, Hof PR, Van Hoesen GW. Multivariate analysis of laminar patterns of neurodegeneration in posterior cingulate cortex in Alzheimer's disease. Exp Neurol. 1998 Sep; 153(1):8-22.
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  100. Mockus SM, Vrana KE. Advances in the molecular characterization of tryptophan hydroxylase. J Mol Neurosci. 1998 Jun; 10(3):163-79.
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  101. Schwartz J, Van de Pavert S, Clarke I, Rao A, Ray D, Vrana K. Paracrine interactions within the pituitary gland. Ann N Y Acad Sci. 1998 May 15; 839:239-43.
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  102. Gioia L, Vogt LJ, Freeman WM, Flood A, Vogt BA, Vrana KE. PCR-based apolipoprotein E genotype analysis from archival fixed brain. J Neurosci Methods. 1998 Apr 30; 80(2):209-14.
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  103. Aschner M, Stark S, Vrana KE, Conklin DR. Acidosis-induced metallothionein (MT) mRNA expression in neonatal rat primary astrocyte cultures. Neurotoxicology. 1998 Apr; 19(2):227-36.
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  104. Mockus SM, Yohrling GJ, Vrana KE. Tyrosine hydroxylase and tryptophan hydroxylase do not form heterotetramers. J Mol Neurosci. 1998 Feb; 10(1):45-51.
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  105. Mockus SM, Kumer SC, Vrana KE. Carboxyl terminal deletion analysis of tryptophan hydroxylase. Biochim Biophys Acta. 1997 Oct 17; 1342(2):132-40.
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  106. Kumer SC, Mockus SM, Rucker PJ, Vrana KE. Amino-terminal analysis of tryptophan hydroxylase: protein kinase phosphorylation occurs at serine-58. J Neurochem. 1997 Oct; 69(4):1738-45.
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  107. Mockus SM, Kumer SC, Vrana KE. A chimeric tyrosine/tryptophan hydroxylase. The tyrosine hydroxylase regulatory domain serves to stabilize enzyme activity. J Mol Neurosci. 1997 Aug; 9(1):35-48.
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  108. van de Pavert SA, Clarke IJ, Rao A, Vrana KE, Schwartz J. Effects of vasopressin and elimination of corticotropin-releasing hormone-target cells on pro-opiomelanocortin mRNA levels and adrenocorticotropin secretion in ovine anterior pituitary cells. J Endocrinol. 1997 Jul; 154(1):139-47.
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  109. Xu Y, Stokes AH, Freeman WM, Kumer SC, Vogt BA, Vrana KE. Tyrosinase mRNA is expressed in human substantia nigra. Brain Res Mol Brain Res. 1997 Apr; 45(1):159-62.
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  110. Yan Z, Vrana S, Vrana K, Song W-J, Surmeier DJ. Receptor Localization: Laboratory Methods and Procedures. Ariano MA, ed.). The Application of RT-PCR Techniques to the Analysis of mRNA in Tissue and Single Cells. 1997; 160-181.
  111. Vrana SL, Vrana KE. Drug Addiction and its Treatment: Nexus of Neuroscience and Behavior. Johnson B and Roache J (eds.). Substance Abuse and Gene Expression. 1997; 317-338.
  112. Stokes AH, Brown BG, Lee CK, Doolittle DJ, Vrana KE. Tyrosinase enhances the covalent modification of DNA by dopamine. Brain Res Mol Brain Res. 1996 Nov; 42(1):167-70.
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  113. Vrana KE. Advancing technologies in gene amplification. Trends Biotechnol. 1996 Nov; 14(11):413-5.
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  114. Kumer SC, Vrana KE. Intricate regulation of tyrosine hydroxylase activity and gene expression. J Neurochem. 1996 Aug; 67(2):443-62.
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  115. Freeman WM, Vrana SL, Vrana KE. Use of elevated reverse transcription reaction temperatures in RT-PCR. Biotechniques. 1996 May; 20(5):782-3.
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  116. Stokes AH, Brown BG, Lee CK, Doolittle DJ, Vrana KE. Neurodegenerative Disease - Molecular and Cellular Mechanisms and Therapeutic Advances (Fiskum G ed.). Dopamine Covalently Modifies DNA in a Tyrosinase-Enhanced Manner. 1996; 299-304.
  117. Vrana SL, Kluttz BW, Vrana KE. Application of quantitative RT-PCR to the analysis of dopamine receptor mRNA levels in rat striatum. Brain Res Mol Brain Res. 1995 Dec 1; 34(1):127-34.
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  118. Kluttz BW, Vrana KE, Dworkin SI, Childers SR. Effects of morphine on forskolin-stimulated pro-enkephalin mRNA levels in rat striatum: a model for acute and chronic opioid actions in brain. Brain Res Mol Brain Res. 1995 Sep; 32(2):313-20.
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  119. Dopke KL, Vrana KE, Vogt LJ, Vogt BA. AF-DX 384 binding in rabbit cingulate cortex: two site kinetics and section autoradiography. J Pharmacol Exp Ther. 1995 Jul; 274(1):562-9.
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  120. Vrana KE, Walker SJ, Rucker P, Liu X. A carboxyl terminal leucine zipper is required for tyrosine hydroxylase tetramer formation. J Neurochem. 1994 Dec; 63(6):2014-20.
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  121. Walker SJ, Liu X, Roskoski R, Vrana KE. Catalytic core of rat tyrosine hydroxylase: terminal deletion analysis of bacterially expressed enzyme. Biochim Biophys Acta. 1994 May 18; 1206(1):113-9.
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  122. Vrana KE, Rucker PJ, Kumer SC. Recombinant rabbit tryptophan hydroxylase is a substrate for cAMP-dependent protein kinase. Life Sci. 1994; 55(13):1045-52.
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  123. Vrana SL, Vrana KE, Koves TR, Smith JE, Dworkin SI. Chronic cocaine administration increases CNS tyrosine hydroxylase enzyme activity and mRNA levels and tryptophan hydroxylase enzyme activity levels. J Neurochem. 1993 Dec; 61(6):2262-8.
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  124. Walker SJ, Vrana KE. Pituitary corticotroph function during the stress hyporesponsive period in neonatal rats. Neuroendocrinology. 1993 Jun; 57(6):1003-10.
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  125. Vrana SL, Dworkin SI, Vrana KE. Radioenzymatic assay for tryptophan hydroxylase: [3H]H2O release assessed by charcoal adsorption. J Neurosci Methods. 1993 Jun; 48(1-2):123-9.
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  126. Huffman L, Michalkiewicz M, Vrana KE, Hedge GA. Expression of preproNPY and precursor VIP mRNAs in rats under hypo- or hyperthyroid conditions. Mol Cell Neurosci. 1992 Oct; 3(5):418-24.
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  127. Vrana SL, Azzaro AJ, Vrana KE. Chronic selegiline administration transiently decreases tyrosine hydroxylase activity and mRNA in the rat nigrostriatal pathway. Mol Pharmacol. 1992 May; 41(5):839-44.
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  128. Lamport-Vrana SJ, Vrana KE, Fedan JS. Involvement of ecto-phosphoryl transfer in contractions of the smooth muscle of the guinea pig vas deferens to adenosine 5'-triphosphate. J Pharmacol Exp Ther. 1991 Jul 1; 258(1):339-48.
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  129. Liu X, Vrana KE. Leucine zippers and coiled-coils in the aromatic amino acid hydroxylases. Neurochem Int. 1991; 18(1):27-31.
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  130. Roskoski R, Wilgus H, Vrana KE. Inactivation of tyrosine hydroxylase by pterin substrates following phosphorylation by cyclic AMP-dependent protein kinase. Mol Pharmacol. 1990 Oct; 38(4):541-6.
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  131. Liu X, Giza CC, Vrana KE. High efficiency transient expression of eukaryotic genes: use of an HSV-1 immediate early promoter (ICP4). Biotechniques. 1990 Aug; 9(2):168-73.
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  132. Ardekani AM, Walker SJ, Donohue SJ, Stitzel RE, Connors JM, Vrana KE. Adrenocorticotropin and corticosterone levels in pre-weanling spontaneously hypertensive rats. Life Sci. 1989; 44(14):919-25.
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  133. Vrana KE, Churchill ME, Tullius TD, Brown DD. Mapping functional regions of transcription factor TFIIIA. Mol Cell Biol. 1988 Apr; 8(4):1684-96.
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  134. Kubinec J, Vrana KE, Roskoski R. Paraoxon-induced decrease in the muscarinic acetylcholine receptor content in rat heart. Eur J Pharmacol. 1987 Apr 29; 136(3):295-301.
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  135. Vrana KE, Roskoski R. Tyrosine hydroxylase inactivation following cAMP-dependent phosphorylation activation. J Neurochem. 1983 Jun; 40(6):1692-700.
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  136. Cook PF, Neville ME, Vrana KE, Hartl FT, Roskoski R. Adenosine cyclic 3',5'-monophosphate dependent protein kinase: kinetic mechanism for the bovine skeletal muscle catalytic subunit. Biochemistry. 1982 Nov 9; 21(23):5794-9.
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  137. Vrana KE, Allhiser CL, Roskoski R. Tyrosine hydroxylase activation and inactivation by protein phosphorylation conditions. J Neurochem. 1981 Jan; 36(1):92-100.
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