David B. Morton, Ph.D., B.A.

  • Professor of Integrative Biosciences, School of Dentistry
  • Cell and Developmental Biology Graduate Program, School of Medicine
  • Neuroscience Graduate Program, School of Medicine
  • Program in Molecular and Cellular Biosciences, School of Medicine

Biography

Research Interests

The majority of the research projects in my laboratory focus on understanding molecular and cellular signaling pathways in the nervous system using the fruit fly Drosophila melanogaster as a model system. The unparalleled array of genetic tools that are available in Drosophila make it an invaluable system for unraveling the molecular and cellular basis of normal functioning of the human brain and the underlying mechanisms of disease. Three primary projects are currently ongoing in the lab:

Cyclic GMP signaling and neuronal hypoxia sensing

All animals require oxygen to survive and it is critical for an organism to be able to respond rapidly and appropriately to hypoxic conditions. My lab has been studying the function and regulation of the intracellular messenger, cyclic GMP (cGMP) for over 30yrs and we identified a novel class of guanylyl cyclases, the enzymes that synthesize cGMP, which are regulated by changes in oxygen levels. In Drosophila these enzymes are located throughout the nervous system, and in particular in sensory neurons, where they function as neuronal hypoxia detectors. When these neurons are activated in hypoxic conditions they signal to the CNS to initiate behavioral escape responses.

Molecular and cellular basis for Lou Gehrig's disease

Amyotrophic lateral sclerosis (ALS) or Lou Gehrig's disease is a relentlessly progressive neurodegenerative disease that in most cases leads to death 3-5 years after diagnosis. ALS is caused by the selective degeneration of motor neurons, which in ALS patients contain cytoplasmic protein aggregates containing an RNA-binding protein named TDP-43. We are utilizing the genetic tool kit available in Drosophila to understand the molecular and cellular outcomes of TDP-43 dysfunction that lead to neurodegeneration.

Methamphetamine action on the nervous systemMethamphetamine use is one of the top drug problems in America and is a significant contributor to crime in the United States. We have recently started to use Drosophila to help identify new targets that modulate the action of methamphetamine in the nervous system. We have now shown that the small GTPase, Rab10 modulates the effects of methamphetamine in flies. Future experiments will focus on determining which neurons require Rab10 expression and the function of Rab10 in methamphetamine action.

Education and training

  • Degrees

    • B.A., 1980, The University of Cambridge
    • Ph.D., 1983, The University of Cambridge

Areas of interest

  • Neuroscience
  • Drosophila neurobiology
  • Neurodegeneration
  • Genetics
  • Signal transduction

Honors and awards

  • Fulbright-Hayes Travel Grant
  • 1991 - 1993 Alfred P. Sloan Research Fellowship
  • 1991 NINDS First Award
  • 2000 Dean’s Research Award, School of Dentistry, OHSU
  • 2002, 2007 Finalist, OHSU Faculty Senate Awards in Research
  • 2008 Outstanding Researcher in Biological Science – Sigma Xi, Columbia-Willamette chapter
  • 2012 Finalist, OHSU Faculty Senate Awards in Collaboration
  • 2013 Finalist, OHSU Faculty Senate Awards in Research
  • 2014 Elected honorary member; Omicron Kappa Upsilon Delta

Publications

Selected publications

  • Morton, D.B. (2004).  Atypical soluble guanylyl cyclases in Drosophila can function as molecular oxygen sensors. J. Biol. Chem. 279:50651-50653. PMID: 15485853
  • Morton, D.B. and Vermehren, A. (2007). Soluble Guanylyl Cyclases in Invertebrates: targets for NO and O2. In Advances in Experimental Biology on Nitric Oxide pp 65-82, Eds. B.A. Trimmer and B. Tota, Elsevier Press. PMID: 19122779, PMCID: PMC2613308
  • Morton, D.B., Stewart, J.A., Langlais, K.K., Clemens-Grisham, R. and Vermehren, A. (2008). Synaptic transmission in neurons that express the Drosophila atypical soluble guanylyl cyclases, Gyc-89Da and Gyc-89Db, is necessary for the successful completion of larval and adult ecdysis. J. exp. Biol. 211, 1645-1656. PMID: 18456892, PMCID: PMC2424211
  • Zimmer, M., Gray, J.M., Pokala, N., Chang, A.J., Karow, D.S., Marletta, M.A., Hudson, M.L., Morton, D.B., Chronis, N. and Bargmann, C.I. (2009). Neurons detect increases and decreases in oxygen levels using distinct guanylate cyclases. Neuron 61, 865-879. PMID: 19323996, PMCID: PMC2760494
  • Morton, D. B., Clemens-Grisham, R., Hazelett, D.J. and Vermehren-Schmaedick, A. (2010). Infertility and male mating behavior deficits associated with Pde1c in Drosophila melanogaster. Genetics 186: 159–165. PMID: 20551439, PMCID: PMC2940284
  • Vermehren-Schmaedick, A. Ainsley, J.A., Johnson, W.A., Davies, S-A. and Morton, D.B. (2010). Behavioral responses to hypoxia in Drosophila larvae are mediated by atypical soluble guanylyl cyclases. Genetics 186: 183–196. PMID: 20592263 PMCID: PMC2940286
  • Hazelett, D.J., Chang, J-C., Lakeland, D.L. and Morton, D.B. (2012). Comparison of parallel hi-throughput RNA-sequencing between knockout of TDP-43 and its overexpression reveals primarily non-reciprocal and non-overlapping gene expression changes in the central nervous system of Drosophila. G3:Genes, Genomes, Genetics 2, 789-802. PMID: 22870402, PMCID: PMC3385985.
  • Brown, K.M., Day, J.P., Huston, E., Zimmermann, B., Hampel, K., Christian, F., Romano, D., Terhzaz, S., Lee, L.C.Y., Willis, M.J., Morton, D.B., Beavo, J.A., Shimizu-Albergine, M., Davies, S.A., Kolch, W., Houslay, M.D. and Baillie, G.S. (2013). Phosphodiesterase-8A binds to and regulates Raf-1 kinase. Proc. Natl. Acad. Sci. 110, E1533-42. PMID: 23509299; PMCID: PMC3631629.
  • Vanderwerf, S.M., Buck, D.C., Wilmarth, P.A., David, L.L., Sears, L.M., Morton, D.B. and Neve, K.A. (2015). Role for Rab10 in methamphetamine-induced behavior. PloS One 10(8): e0136167. doi:10.1371. PMID: 26291453; PMCID: PMC4546301.

Publications

  • The ZO-1 protein Polychaetoid as an upstream regulator of the Hippo pathway in Drosophila

    PLoS genetics
    1. Qingliang Sang
    2. Gang Wang
    3. David B. Morton
    4. Hui Wu
    5. Baotong Xie
  • Deletion of a specific exon in the voltage-gated calcium channel gene cacophony disrupts locomotion in Drosophila larvae

    Journal of Experimental Biology
    1. Kayly M. Lembke
    2. Alexander D. Law
    3. Jasmine Ahrar
    4. David B. Morton
  • Opposing transcriptional and post-transcriptional roles for Scalloped in binary Hippo-dependent neural fate decisions

    Developmental Biology
    1. Baotong Xie
    2. David B. Morton
    3. Tiffany A. Cook
  • Drosophila lines with mutant and wild type human TDP-43 replacing the endogenous gene reveals phosphorylation and ubiquitination in mutant lines in the absence of viability or lifespan defects

    PloS one
    1. Jer Cherng Chang
    2. D. B. Morton
  • Exploring the interaction of drosophila TDP-43 and the type ii voltage-gated calcium channel, cacophony, in regulating motor function and behavior

    Journal of Experimental Neuroscience
    1. Kayly M. Lembke
    2. David B. Morton
  • Restoration of motor defects caused by loss of drosophila TDP-43 by expression of the voltage-gated calcium channel, cacophony, in central neurons

    Journal of Neuroscience
    1. Kayly M. Lembke
    2. Charles Scudder
    3. David B. Morton
  • Multifaceted biological insights from a draft genome sequence of the tobacco hornworm moth, Manduca sexta

    Insect Biochemistry and Molecular Biology
    1. Michael R. Kanost
    2. Estela L. Arrese
    3. Xiaolong Cao
    4. Yun Ru Chen
    5. Sanjay Chellapilla
    6. Marian R. Goldsmith
    7. Ewald Grosse-Wilde
    8. David G. Heckel
    9. Nicolae Herndon
    10. Haobo Jiang
    11. Alexie Papanicolaou
    12. Jiaxin Qu
    13. Jose L. Soulages
    14. Heiko Vogel
    15. James Walters
    16. Robert M. Waterhouse
    17. Seung Joon Ahn
    18. Francisca C. Almeida
    19. Chunju An
    20. Peshtewani Aqrawi
    21. Anne Bretschneider
    22. William B. Bryant
    23. Sascha Bucks
    24. Hsu Chao
    25. Germain Chevignon
    26. Jayne M. Christen
    27. David F. Clarke
    28. Neal T. Dittmer
    29. Laura C.F. Ferguson
    30. Spyridoula Garavelou
    31. Karl H.J. Gordon
    32. Ramesh T. Gunaratna
    33. Yi Han
    34. Frank Hauser
    35. Yan He
    36. Hanna Heidel-Fischer
    37. Ariana Hirsh
    38. Yingxia Hu
    39. Hongbo Jiang
    40. Divya Kalra
    41. Christian Klinner
    42. Christopher König
    43. Christie Kovar
    44. Ashley R. Kroll
    45. Suyog S. Kuwar
    46. Sandy L. Lee
    47. Rüdiger Lehman
    48. Kai Li
    49. Zhaofei Li
    50. Hanquan Liang
    51. Shanna Lovelace
    52. Zhiqiang Lu
    53. Jennifer H. Mansfield
    54. Kyle J. McCulloch
    55. Tittu Mathew
    56. Brian Morton
    57. Donna M. Muzny
    58. David Neunemann
    59. Fiona Ongeri
    60. Yannick Pauchet
    61. Ling Ling Pu
    62. Ioannis Pyrousis
    63. Xiang Jun Rao
    64. Amanda Redding
    65. Charles Roesel
    66. Alejandro Sanchez-Gracia
    67. Sarah Schaack
    68. Aditi Shukla
    69. Guillaume Tetreau
    70. Yang Wang
    71. Guang Hua Xiong
    72. Walther Traut
    73. Tom K. Walsh
    74. Kim C. Worley
    75. Di Wu
    76. Wenbi Wu
    77. Yuan Qing Wu
    78. Xiufeng Zhang
    79. Zhen Zou
    80. Hannah Zucker
    81. Adriana D. Briscoe
    82. Thorsten Burmester
    83. Rollie J. Clem
    84. René Feyereisen
    85. Cornelis J.P. Grimmelikhuijzen
    86. Stavros J. Hamodrakas
    87. Bill S. Hansson
    88. Elisabeth Huguet
    89. Lars S. Jermiin
    90. Que Lan
    91. Herman K. Lehman
    92. Marce Lorenzen
    93. Hans Merzendorfer
    94. Ioannis Michalopoulos
    95. David B. Morton
    96. Subbaratnam Muthukrishnan
    97. John G. Oakeshott
    98. Will Palmer
    99. Yoonseong Park
    100. A. Lorena Passarelli
    101. Julio Rozas
    102. Lawrence M. Schwartz
    103. Wendy Smith
    104. Agnes Southgate
    105. Andreas Vilcinskas
    106. Richard Vogt
    107. Ping Wang
    108. John Werren
    109. Xiao Qiang Yu
    110. Jing Jiang Zhou
    111. Susan J. Brown
    112. Steven E. Scherer
    113. Stephen Richards
    114. Gary W. Blissard
  • Role for Rab10 in methamphetamine-induced behavior

    PloS one
    1. Scott M. Vanderwerf
    2. David C. Buck
    3. Phillip A. Wilmarth
    4. Leila M. Sears
    5. Larry L. David
    6. David B. Morton
    7. Kim A. Neve
  • Motor neuron expression of the voltage-gated calcium channel cacophony restores locomotion defects in a Drosophila, TDP-43 loss of function model of ALS

    Brain research
    1. Jer Cherng Chang
    2. Dennis J. Hazelett
    3. Judith A. Stewart
    4. David B. Morton
  • Phosphodiesterase-8A binds to and regulates Raf-1 kinase

    Proceedings of the National Academy of Sciences of the United States of America
    1. Kim M. Brown
    2. Jon P. Day
    3. Elaine Huston
    4. Bastian Zimmermann
    5. Kornelia Hampel
    6. Frank Christian
    7. David Romano
    8. Selim Terhzaz
    9. Louisa C.Y. Lee
    10. Miranda J. Willis
    11. David B. Morton
    12. Joseph A. Beavo
    13. Masami Shimizu-Albergine
    14. Shireen A. Davies
    15. Walter Kolch
    16. Miles D. Houslay
    17. George S. Baillie
  • Comparison of parallel high-throughput RNA sequencing between knockout of TDP-43 and its overexpression reveals primarily nonreciprocal and nonoverlapping gene expression changes in the central nervous system of drosophila

    G3: Genes, Genomes, Genetics
    1. Dennis J. Hazelett
    2. Jer Cherng Chang
    3. Daniel L. Lakeland
    4. David B. Morton
  • Behavioral responses to hypoxia and hyperoxia in Drosophila larvae molecular and neuronal sensors

    Fly
    1. David B. Morton
  • Drosophila gustatory preference behaviors require the atypical soluble guanylyl cyclases

    Journal of Comparative Physiology A: Neuroethology, Sensory, Neural, and Behavioral Physiology
    1. Anke Vermehren-Schmaedick
    2. Charles Scudder
    3. Wendy Timmermans
    4. David B. Morton
  • Response properties of visual neurons in the turtle nucleus isthmi

    Journal of Comparative Physiology A: Neuroethology, Sensory, Neural, and Behavioral Physiology
    1. Debajit Saha
    2. David Morton
    3. Michael Ariel
    4. Ralf Wessel
  • Behavioral responses to hypoxia in drosophila larvae are mediated by atypical soluble guanylyl cyclases

    Genetics
    1. Anke Vermehren-Schmaedick
    2. Joshua A. Ainsley
    3. Wayne A. Johnson
    4. Shireen A. Davies
    5. David B. Morton
  • Infertility and male mating behavior deficits associated with Pde1c in Drosophila melanogaster

    Genetics
    1. David B. Morton
    2. Rachel Clemens-Grisham
    3. Dennis J. Hazelett
    4. Anke Vermehren-Schmaedick
  • Neurons Detect Increases and Decreases in Oxygen Levels Using Distinct Guanylate Cyclases

    Neuron
    1. Manuel Zimmer
    2. Jesse M. Gray
    3. Navin Pokala
    4. Andy J. Chang
    5. David S. Karow
    6. Michael A. Marletta
    7. Martin L. Hudson
    8. David B. Morton
    9. Nikos Chronis
    10. Cornelia I. Bargmann
  • Synaptic transmission in neurons that express the Drosophila atypical soluble guanylyl cyclases, Gyc-89Da and Gyc-89Db, is necessary for the successful completion of larval and adult ecdysis

    Journal of Experimental Biology
    1. David B. Morton
    2. Judith A. Stewart
    3. Kristofor K. Langlais
    4. Rachel A. Clemens-Grisham
    5. Anke Vermehren
  • Comparison of the properties of the five soluble guanylyl cyclase subunits in Drosophila melanogaster

    Journal of Insect Science
    1. David B. Morton
    2. Kristofor K. Langlais
    3. Judith A. Stewart
    4. Anke Vermehren
  • Atypical soluble guanylyl cyclases in Drosophila can function as molecular oxygen sensors

    Journal of Biological Chemistry
    1. David B. Morton
  • Preliminary characterization of two atypical soluble guanylyl cyclases in the central and peripheral nervous system of Drosophila melanogaster

    Journal of Experimental Biology
    1. Kristofor K. Langlais
    2. Judith A. Stewart
    3. David B. Morton
  • MsGC-II, a receptor guanylyl cyclase isolated from the CNS of Manduca sexta that is inhibited by calcium

    Journal of neurochemistry
    1. David B. Morton
    2. Alan Nighorn
  • MsGC-β3 forms active homodimers and inactive heterodimers with NO-sensitive soluble guanylyl cyclase subunits

    Journal of Experimental Biology
    1. David B. Morton
    2. Esther J. Anderson
  • Nicotinic-acetylcholine receptors are functionally coupled to the nitric oxide/cGMP-pathway in insect neurons

    Journal of neurochemistry
    1. Ricardo M. Zayas
    2. Sanjive Qazi
    3. David B. Morton
    4. Barry A. Trimmer