Dona M. Chikaraishi | Scholars@Duke

Dona M. Chikaraishi
Professor Emeritus of Neurobiology

Dr. Chikaraishi's laboratory studies the role of catecholamine neurotransmitters (dopamine, norepinephrine and epinephrine) during development. Catecholamine-deficient mice die at mid-gestation (E12.5), long before catecholamine neurons participate in neurotransmission, suggesting that catecholamines serve an unappreciated role in fetal survival.

Using physiological and pharmacological approaches, the laboratory has shown that catecholamines, particularly norepinephrine, maintain cardiovascular function in the fetus by regulating heart rate and contractility. This requirement is critical during hypoxia, which occurs throughout gestation due to spontaneous uterine contractions. Experimentally induced hypoxia preferentially kills catecholamine-deficient fetuses compared to wild type or heterozygous siblings in a time and dose-dependent manner. In vivo and in culture, hypoxia slows fetal heart rate and this bradycardia is exacerbated by blocking b1 adrenergic receptors. In isolated cultured hearts, where endogenous norepinephrine is absent, hypoxia also slows heart rate and this bradycardia can be reversed by activating b adrenergic receptors. It is likely that fetal survival is due to the cardiovascular requirement for b adrenergic activation because lethality of catecholamine-deficient animals is completely reversed by b adrenergic agonists administered via the pregnant dam.

The working hypothesis is that hypoxia reduces heart rate but also induces systemic norepinephrine release, which increases cardiac output via b adrenergic receptor activation. Restoration of cardiovascular function by norepinephrine allows the fetus to survive transient bouts of hypoxia in utero. Hence, catecholamines serve an acute and essential role in the fetus to maintain cardiovascular function. The critical catecholamine, norepinephrine, may act through a novel fetal b receptor to support survival.

Current Appointments & Affiliations

Professor Emeritus of Neurobiology, Neurobiology, Basic Science Departments 2015
Associate Dean for Biomedical Grad Educ and Leadership, School of Medicine, Duke University 2008
Faculty Network Member of the Duke Institute for Brain Sciences, Duke Institute for Brain Sciences, University Institutes and Centers 2008

Contact Information

2034 GSRB 1, 905 Lasalle, Durham, NC 27710
Box 103855 Med Ctr, Durham, NC 27710
donam@neuro.duke.edu (919) 681-4269

Background
Education, Training, & Certifications
- Ph.D., University of California - San Diego 1973
Duke Appointment History
- Professor of Neurobiology, Neurobiology, Basic Science Departments 1996 - 2015
- Instructor, Temporary of Neurobiology, Neurobiology, Basic Science Departments 1995 - 1996
Research
Selected Grants
- Molecular Basis Of Tyrosine Hydroxylase Regulation awarded by National Institutes of Health 1999 - 2005
- Effect of catecholamines on embryonic development awarded by National Institutes of Health 2001 - 2002
- Catecholamines effect on embryonic development awarded by National Institutes of Health 2000 - 2001
- Effect of Catecholamines on Embryonic Cardiovascular Function awarded by National Institutes of Health 1999 - 2001
Publications & Artistic Works
Selected Publications
- Academic Articles
  - Ream, Margie A., Rashmi Chandra, Mary Peavey, Alisa M. Ray, Suzanne Roffler-Tarlov, Hyung-Gun Kim, William C. Wetsel, Howard A. Rockman, and Dona M. Chikaraishi. “High oxygen prevents fetal lethality due to lack of catecholamines.” Am J Physiol Regul Integr Comp Physiol 295, no. 3 (September 2008): R942–53. https://doi.org/10.1152/ajpregu.00860.2007.
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  - Ream, Margie, Alisa M. Ray, Rashmi Chandra, and Dona M. Chikaraishi. “Early fetal hypoxia leads to growth restriction and myocardial thinning.” Am J Physiol Regul Integr Comp Physiol 295, no. 2 (August 2008): R583–95. https://doi.org/10.1152/ajpregu.00771.2007.
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  - Kelly, B. B., E. Hedlund, C. Kim, H. Ishiguro, O. Isacson, D. M. Chikaraishi, K. -. S. Kim, and G. Feng. “A tyrosine hydroxylase-yellow fluorescent protein knock-in reporter system labeling dopaminergic neurons reveals potential regulatory role for the first intron of the rodent tyrosine hydroxylase gene.” Neuroscience 142, no. 2 (October 13, 2006): 343–54. https://doi.org/10.1016/j.neuroscience.2006.06.032.
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  - Chandra, Rashmi, Andrea L. Portbury, Alisa Ray, Margie Ream, Marybeth Groelle, and Dona M. Chikaraishi. “Beta1-adrenergic receptors maintain fetal heart rate and survival.” Biol Neonate 89, no. 3 (2006): 147–58. https://doi.org/10.1159/000088842.
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  - Osterhout, Cheryl A., Carol R. Sterling, Dona M. Chikaraishi, and A William Tank. “Induction of tyrosine hydroxylase in the locus coeruleus of transgenic mice in response to stress or nicotine treatment: lack of activation of tyrosine hydroxylase promoter activity.” J Neurochem 94, no. 3 (August 2005): 731–41. https://doi.org/10.1111/j.1471-4159.2005.03222.x.
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  - Marchand, James E., Xinhai Yang, Dona Chikaraishi, Jurgen Krieger, Heinz Breer, and John S. Kauer. “Olfactory receptor gene expression in tiger salamander olfactory epithelium.” J Comp Neurol 474, no. 3 (June 28, 2004): 453–67. https://doi.org/10.1002/cne.20161.
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  - Lewis-Tuffin, Laura J., Patrick G. Quinn, and Dona M. Chikaraishi. “Tyrosine hydroxylase transcription depends primarily on cAMP response element activity, regardless of the type of inducing stimulus.” Mol Cell Neurosci 25, no. 3 (March 2004): 536–47. https://doi.org/10.1016/j.mcn.2003.10.010.
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  - Portbury, Andrea L., Rashmi Chandra, Marybeth Groelle, Michael K. McMillian, Alana Elias, James R. Herlong, Maribel Rios, Suzanne Roffler-Tarlov, and Dona M. Chikaraishi. “Catecholamines act via a beta-adrenergic receptor to maintain fetal heart rate and survival.” Am J Physiol Heart Circ Physiol 284, no. 6 (June 2003): H2069–77. https://doi.org/10.1152/ajpheart.00588.2002.
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  - Horton, C. D., Y. Qi, D. Chikaraishi, and J. K. Wang. “Neurotrophin-3 mediates the autocrine survival of the catecholaminergic CAD CNS neuronal cell line.” J Neurochem 76, no. 1 (January 2001): 201–9. https://doi.org/10.1046/j.1471-4159.2001.00017.x.
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  - Schimmel, J. J., L. Crews, S. Roffler-Tarlov, and D. M. Chikaraishi. “4.5 kb of the rat tyrosine hydroxylase 5' flanking sequence directs tissue specific expression during development and contains consensus sites for multiple transcription factors.” Brain Res Mol Brain Res 74, no. 1–2 (December 10, 1999): 1–14. https://doi.org/10.1016/s0169-328x(99)00234-x.
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  - Rios, M., B. Habecker, T. Sasaoka, G. Eisenhofer, H. Tian, S. Landis, D. Chikaraishi, and S. Roffler-Tarlov. “Catecholamine synthesis is mediated by tyrosinase in the absence of tyrosine hydroxylase.” J Neurosci 19, no. 9 (May 1, 1999): 3519–26.
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  - Lazaroff, M., Y. Qi, and D. M. Chikaraishi. “Differentiation of a catecholaminergic CNS cell line modifies tyrosine hydroxylase transcriptional regulation.” J Neurochem 71, no. 1 (July 1998): 51–59. https://doi.org/10.1046/j.1471-4159.1998.71010051.x.
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  - Sun, D., D. M. Chikaraishi, and R. K. H. Liem. “Expression of intermediate filament proteins and specific induction of alpha-internexin in a CNS cell line, CAD, upon differentiation.” Molecular Biology of the Cell 8 (November 1, 1997): 1612–1612.
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  - Thukral, V., D. Chikaraishi, D. D. Hunter, and J. K. Wang. “Expression of non-N-methyl-D-aspartate glutamate receptor subunits in the olfactory epithelium.” Neuroscience 79, no. 2 (July 1997): 411–24. https://doi.org/10.1016/s0306-4522(96)00699-9.
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  - Patankar, S., M. Lazaroff, S. O. Yoon, and D. M. Chikaraishi. “A novel basal promoter element is required for expression of the rat tyrosine hydroxylase gene.” J Neurosci 17, no. 11 (June 1, 1997): 4076–86.
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  - Osterhout, C. A., D. M. Chikaraishi, and A. W. Tank. “Induction of tyrosine hydroxylase protein and a transgene containing tyrosine hydroxylase 5' flanking sequences by stress in mouse adrenal gland.” J Neurochem 68, no. 3 (March 1997): 1071–77. https://doi.org/10.1046/j.1471-4159.1997.68031071.x.
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  - Qi, Y., J. K. Wang, M. McMillian, and D. M. Chikaraishi. “Characterization of a CNS cell line, CAD, in which morphological differentiation is initiated by serum deprivation.” J Neurosci 17, no. 4 (February 15, 1997): 1217–25.
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  - Lazaroff, M., K. Dunlap, and D. M. Chikaraishi. “A CNS catecholaminergic cell line expresses voltage-gated currents.” J Membr Biol 151, no. 3 (June 1996): 279–91. https://doi.org/10.1007/s002329900078.
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  - Lazaroff, M., S. Patankar, S. O. Yoon, and D. M. Chikaraishi. “The cyclic AMP response element directs tyrosine hydroxylase expression in catecholaminergic central and peripheral nervous system cell lines from transgenic mice.” J Biol Chem 270, no. 37 (September 15, 1995): 21579–89. https://doi.org/10.1074/jbc.270.37.21579.
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  - Szabo, M., M. R. Butz, S. A. Banerjee, D. M. Chikaraishi, and L. A. Frohman. “Autofeedback suppression of growth hormone (GH) secretion in transgenic mice expressing a human GH reporter targeted by tyrosine hydroxylase 5'-flanking sequences to the hypothalamus.” Endocrinology 136, no. 9 (September 1995): 4044–48. https://doi.org/10.1210/endo.136.9.7649113.
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  - Wensley, C. H., D. M. Stone, H. Baker, J. S. Kauer, F. L. Margolis, and D. M. Chikaraishi. “Olfactory marker protein mRNA is found in axons of olfactory receptor neurons.” J Neurosci 15, no. 7 Pt 1 (July 1995): 4827–37.
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  - Yoon, S. O., and D. M. Chikaraishi. “Isolation of two E-box binding factors that interact with the rat tyrosine hydroxylase enhancer.” J Biol Chem 269, no. 28 (July 15, 1994): 18453–62.
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  - Banerjee, S. A., S. Roffler-Tarlov, M. Szabo, L. Frohman, and D. M. Chikaraishi. “DNA regulatory sequences of the rat tyrosine hydroxylase gene direct correct catecholaminergic cell-type specificity of a human growth hormone reporter in the CNS of transgenic mice causing a dwarf phenotype.” Brain Res Mol Brain Res 24, no. 1–4 (July 1994): 89–106. https://doi.org/10.1016/0169-328x(94)90121-x.
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  - Dawson, S. J., S. O. Yoon, D. M. Chikaraishi, K. A. Lillycrop, and D. S. Latchman. “The Oct-2 transcription factor represses tyrosine hydroxylase expression via a heptamer TAATGARAT-like motif in the gene promoter.” Nucleic Acids Res 22, no. 6 (March 25, 1994): 1023–28. https://doi.org/10.1093/nar/22.6.1023.
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  - CHIKARAISHI, D. M., S. O. YOON, C. SURI, S. BANERJEE, and M. LAZAROFF. “TYROSINE-HYDROXYLASE REGULATION IN CULTURED-CELLS AND IN MICE.” Journal of Neurochemistry 62 (January 1, 1994): S62–S62.
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  - Fung, K. M., D. M. Chikaraishi, C. Suri, F. Theuring, A. Messing, D. M. Albert, V. M. Lee, and J. Q. Trojanowski. “Molecular phenotype of simian virus 40 large T antigen-induced primitive neuroectodermal tumors in four different lines of transgenic mice.” Lab Invest 70, no. 1 (January 1994): 114–24.
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  - Suri, C., B. P. Fung, A. S. Tischler, and D. M. Chikaraishi. “Catecholaminergic cell lines from the brain and adrenal glands of tyrosine hydroxylase-SV40 T antigen transgenic mice.” J Neurosci 13, no. 3 (March 1993): 1280–91.
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  - Banerjee, S. A., P. Hoppe, M. Brilliant, and D. M. Chikaraishi. “5' flanking sequences of the rat tyrosine hydroxylase gene target accurate tissue-specific, developmental, and transsynaptic expression in transgenic mice.” J Neurosci 12, no. 11 (November 1992): 4460–67.
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  - Yoon, S. O., and D. M. Chikaraishi. “Tissue-specific transcription of the rat tyrosine hydroxylase gene requires synergy between an AP-1 motif and an overlapping E box-containing dyad.” Neuron 9, no. 1 (July 1992): 55–67. https://doi.org/10.1016/0896-6273(92)90220-8.
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  - Fung, B. P., S. O. Yoon, and D. M. Chikaraishi. “Sequences that direct rat tyrosine hydroxylase gene expression.” J Neurochem 58, no. 6 (June 1992): 2044–52. https://doi.org/10.1111/j.1471-4159.1992.tb10945.x.
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  - Schwartz Levey, M., D. M. Chikaraishi, and J. S. Kauer. “Characterization of potential precursor populations in the mouse olfactory epithelium using immunocytochemistry and autoradiography.” J Neurosci 11, no. 11 (November 1991): 3556–64.
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  - Fung, B. P., M. H. Brilliant, and D. M. Chikaraishi. “Brain-specific polyA- transcripts are detected in polyA+ RNA: do complex polyA- brain RNAs really exist?” J Neurosci 11, no. 3 (March 1991): 701–8.
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  - Calof, A. L., A. D. Lander, and D. M. Chikaraishi. “Regulation of neurogenesis and neuronal differentiation in primary and immortalized cells from mouse olfactory epithelium.” Ciba Found Symp 160 (1991): 249–65. https://doi.org/10.1002/9780470514122.ch13.
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  - Wu, J. K., and D. M. Chikaraishi. “Differential expression of ros oncogene in primary human astrocytomas and astrocytoma cell lines.” Cancer Res 50, no. 10 (May 15, 1990): 3032–35.
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  - Jones, K. J., C. A. Harrington, D. M. Chikaraishi, and D. W. Pfaff. “Steroid hormone regulation of ribosomal RNA in rat hypothalamus: early detection using in situ hybridization and precursor-product ribosomal DNA probes.” J Neurosci 10, no. 5 (May 1990): 1513–21.
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  - Cambi, F., B. Fung, and D. Chikaraishi. “5' flanking DNA sequences direct cell-specific expression of rat tyrosine hydroxylase.” J Neurochem 53, no. 5 (November 1989): 1656–59. https://doi.org/10.1111/j.1471-4159.1989.tb08567.x.
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  - Morrell, J. I., M. F. Rosenthal, J. T. McCabe, C. A. Harrington, D. M. Chikaraishi, and D. W. Pfaff. “Tyrosine hydroxylase mRNA in the neurons of the tuberoinfundibular region and zona incerta examined after gonadal steroid hormone treatment.” Mol Endocrinol 3, no. 9 (September 1989): 1426–33. https://doi.org/10.1210/mend-3-9-1426.
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  - Calof, A. L., and D. M. Chikaraishi. “Analysis of neurogenesis in a mammalian neuroepithelium: proliferation and differentiation of an olfactory neuron precursor in vitro.” Neuron 3, no. 1 (July 1989): 115–27. https://doi.org/10.1016/0896-6273(89)90120-7.
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  - Kawata, M., J. T. McCabe, C. Harrington, D. Chikaraishi, and D. W. Pfaff. “In situ hybridization analysis of osmotic stimulus-induced changes in ribosomal RNA in rat supraoptic nucleus.” J Comp Neurol 270, no. 4 (April 22, 1988): 528–36. https://doi.org/10.1002/cne.902700406.
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  - Lewis, E. J., and D. M. Chikaraishi. “Regulated expression of the tyrosine hydroxylase gene by epidermal growth factor.” Mol Cell Biol 7, no. 9 (September 1987): 3332–36. https://doi.org/10.1128/mcb.7.9.3332-3336.1987.
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  - Phillips, L. L., S. J. Nostrandt, D. M. Chikaraishi, and O. Steward. “Increases in ribosomal RNA within the denervated neuropil of the dentate gyrus during reinnervation: evaluation by in situ hybridization using DNA probes complementary to ribosomal RNA.” Brain Res 388, no. 3 (September 1987): 251–61. https://doi.org/10.1016/0169-328x(87)90032-5.
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  - Lewis, E. J., C. A. Harrington, and D. M. Chikaraishi. “Transcriptional regulation of the tyrosine hydroxylase gene by glucocorticoid and cyclic AMP.” Proc Natl Acad Sci U S A 84, no. 11 (June 1987): 3550–54. https://doi.org/10.1073/pnas.84.11.3550.
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  - Harrington, C. A., E. J. Lewis, D. Krzemien, and D. M. Chikaraishi. “Identification and cell type specificity of the tyrosine hydroxylase gene promoter.” Nucleic Acids Res 15, no. 5 (March 11, 1987): 2363–84. https://doi.org/10.1093/nar/15.5.2363.
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  - HARRINGTON, C. A., and D. M. CHIKARAISHI. “GROWTH-REGULATION OF THE TRANSCRIPTION OF RIBOSOMAL-RNA PRECURSOR AND UPSTREAM SPACER SEQUENCES IN RAT RDNA.” Journal of Cellular Biochemistry, January 1, 1987, 78–78.
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  - Harrington, C. A., and D. M. Chikaraishi. “Transcription of spacer sequences flanking the rat 45S ribosomal DNA gene.” Mol Cell Biol 7, no. 1 (January 1987): 314–25. https://doi.org/10.1128/mcb.7.1.314-325.1987.
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  - Jones, K. J., D. M. Chikaraishi, C. A. Harrington, B. S. McEwen, and D. W. Pfaff. “In situ hybridization detection of estradiol-induced changes in ribosomal RNA levels in rat brain.” Brain Res 387, no. 2 (November 1986): 145–52. https://doi.org/10.1016/0169-328x(86)90006-9.
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  - MORRELL, J. I., J. T. MCCABE, C. HARRINGTON, D. M. CHIKARAISHI, and D. W. PFAFF. “NEURONAL AND CHROMAFFIN CELL LOCALIZATION OF TYROSINE HYDROXYLASE-LIKE MESSENGER-RNA USING INSITU HYBRIDIZATION.” Journal of Histochemistry & Cytochemistry 34, no. 10 (October 1, 1986): 1365–1365.
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  - BRILLIANT, M. H., C. A. HARRINGTON, and D. M. CHIKARAISHI. “RARE NONPOLYADENYLATED TRANSCRIPTS UNIQUE TO RAT-BRAIN.” Journal of Cellular Biochemistry, January 1, 1986, 166–166.
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  - Chikaraishi, D. M. “The ID, brain identifier, model of neuronal gene expression: a re-evaluation.” Trends in Neurosciences 9, no. C (January 1, 1986): 543–46. https://doi.org/10.1016/0166-2236(86)90172-4.
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  - MORRELL, J. I., J. T. MCCABE, C. HARRINGTON, D. M. CHIKARAISHI, and D. W. PFAFF. “NEURONAL AND CHROMAFFIN CELL LOCALIZATION OF TYROSINE HYDROXYLASE-LIKE MESSENGER-RNA USING INSITU HYBRIDIZATION.” Acta Histochemica Et Cytochemica 19, no. 3 (January 1, 1986): 395–395.
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  - Tank, A. W., E. J. Lewis, D. M. Chikaraishi, and N. Weiner. “Elevation of RNA coding for tyrosine hydroxylase in rat adrenal gland by reserpine treatment and exposure to cold.” J Neurochem 45, no. 4 (October 1985): 1030–33. https://doi.org/10.1111/j.1471-4159.1985.tb05519.x.
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  - Black, I. B., D. M. Chikaraishi, and E. J. Lewis. “Trans-synaptic increase in RNA coding for tyrosine hydroxylase in a rat sympathetic ganglion.” Brain Res 339, no. 1 (July 22, 1985): 151–53. https://doi.org/10.1016/0006-8993(85)90635-3.
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  - PHILLIPS, L. L., R. A. OGLE, D. M. CHIKARAISHI, and O. STEWARD. “RIBOSOME RE-DISTRIBUTION IN THE DENERVATED DENTATE GYRUS - EVALUATION BY INSITU HYBRIDIZATION USING CDNA PROBES FOR RIBOSOMAL-RNA.” Anatomical Record 211, no. 3 (January 1, 1985): A153–A153.
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  - Brilliant, M. H., N. Sueoka, and D. M. Chikaraishi. “Cloning of DNA corresponding to rare transcripts of rat brain: evidence of transcriptional and post-transcriptional control and of the existence of nonpolyadenylated transcripts.” Mol Cell Biol 4, no. 10 (October 1984): 2187–97. https://doi.org/10.1128/mcb.4.10.2187-2197.1984.
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  - Tomasiewicz, H. G., R. Cook-Deegan, and D. M. Chikaraishi. “Isolation of a cDNA clone complementary to sequences for a 34-kilodalton protein which is a pp60v-src substrate.” Mol Cell Biol 4, no. 9 (September 1984): 1935–38. https://doi.org/10.1128/mcb.4.9.1935-1938.1984.
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  - Lewis, E. J., A. W. Tank, N. Weiner, and D. M. Chikaraishi. “Regulation of tyrosine hydroxylase mRNA by glucocorticoid and cyclic AMP in a rat pheochromocytoma cell line. Isolation of a cDNA clone for tyrosine hydroxylase mRNA.” J Biol Chem 258, no. 23 (December 10, 1983): 14632–37.
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  - Lewis, E. J., A. W. Tank, N. Weiner, and D. M. Chikaraishi. “Regulation of tyrosine hydroxylase mRNA by glucocorticoid and cyclic AMP in a rat pheochromocytoma cell line. Isolation of a cDNA clone for tyrosine hydroxylase mRNA.” The Journal of Biological Chemistry 258, no. 23 (December 1983): 14632–37.
  - Chikaraishi, D. M., L. Buchanan, K. J. Danna, and C. A. Harrington. “Genomic organization of rat rDNA.” Nucleic Acids Res 11, no. 18 (September 24, 1983): 6437–52. https://doi.org/10.1093/nar/11.18.6437.
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  - Harrington, C. A., and D. M. Chikaraishi. “Identification and sequence of the initiation site for rat 45S ribosomal RNA synthesis.” Nucleic Acids Res 11, no. 10 (May 25, 1983): 3317–32. https://doi.org/10.1093/nar/11.10.3317.
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  - Chikaraishi, D. M., M. H. Brilliant, and E. J. Lewis. “Cloning and characterization of rat-brain-specific transcripts: rare, brain-specific transcripts and tyrosine hydroxylase.” Cold Spring Harb Symp Quant Biol 48 Pt 1 (1983): 309–18. https://doi.org/10.1101/sqb.1983.048.01.034.
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  - Beckmann, S. L., D. M. Chikaraishi, S. S. Deeb, and N. Sueoka. “Sequence complexity of nuclear and cytoplasmic ribonucleic acids from clonal neurotumor cell lines and brain sections of the rat.” Biochemistry 20, no. 9 (April 28, 1981): 2684–92. https://doi.org/10.1021/bi00512a050.
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  - Chikaraishi, D. M., and K. J. Danna. “Simian virus 40 transcriptional complexes incorporate mercurated nucleotides into RNA in vitro.” J Virol 37, no. 1 (January 1981): 511–17. https://doi.org/10.1128/JVI.37.1.511-517.1981.
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  - Chikaraishi, D. M. “Complexity of cytoplasmic polyadenylated and nonpolyadenylated rat brain ribonucleic acids.” Biochemistry 18, no. 15 (July 24, 1979): 3249–56. https://doi.org/10.1021/bi00582a009.
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  - Chikaraishi, D. M., S. S. Deeb, and N. Sueoka. “Sequence complexity of nuclear RNAs in adult rat tissues.” Cell 13, no. 1 (January 1978): 111–20. https://doi.org/10.1016/0092-8674(78)90142-3.
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- Conference Papers
  - CALOF, A. L., A. D. LANDER, and D. M. CHIKARAISHI. “REGULATION OF NEUROGENESIS AND NEURONAL DIFFERENTIATION IN PRIMARY AND IMMORTALIZED CELLS FROM MOUSE OLFACTORY EPITHELIUM.” In Regeneration of Vertebrate Sensory Receptor Cells, 160:249–76, 1991.
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Education, Training, & Certifications

Duke Appointment History

Selected Grants

Selected Publications

Academic Articles

Conference Papers