Photo of David B. Morton, BA, Ph.D.

David B. Morton BA, Ph.D.

  • Portland Campus

    • Professor of Integrative Biosciences School of Dentistry
    • Associate Dean for Research Dean's Office 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

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.

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Areas of interest

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

Education

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

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

  • "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 July 2012
  • "Octopamine release from an identified neurone in the locust" Journal of Experimental Biology  1984
  • "Soluble guanylyl cyclases in Caenorhabditis elegans" Current Biology August 12 1999
  • "Infertility and male mating behavior deficits associated with Pde1c in Drosophila melanogaster" Genetics September 2010
  • "Norepinephrine increases cyclic GMP levels in cerebellar cells from neuronal nitric oxide synthase knockout mice" Journal of Neurochemistry July 1998
  • "Eclosion hormone-stimulated cGMP levels in the central nervous system of Manduca sexta" Journal of Comparative Physiology B: Biochemical, Systemic, and Environmental Physiology December 1995
  • "Expression of a developmentally regulated gene, Mng10, in identified neurosecretory cells in the CNS of Manduca sexta" Developmental Neurobiology July 1996
  • "Comparison of the properties of the five soluble guanylyl cyclase subunits in Drosophila melanogaster" Journal of Insect Science April 19 2005
  • "The novel guanylyl cyclase MsGC-I is strongly expressed in higher-order neuropils in the brain of Manduca sexta" Journal of Experimental Biology  2001
  • "Insect physiology" Current Biology  1996
  • "Behavioral responses to hypoxia and hyperoxia in Drosophila larvae molecular and neuronal sensors" Fly April 2011
  • "Isolation and partial characterization of a gene from trachea of Manduca sexta that requires and is negatively regulated by ecdysteroids" Developmental Biology  1994
  • "Up- and downregulation of esr20, an ecdysteroid-regulated gene expressed in the tracheae of Manduca sexta" Archives of Insect Biochemistry and Physiology  1997
  • "Cellular signaling in eclosion hormone action" Journal of Insect Physiology  2002
  • "MsGC-II, a receptor guanylyl cyclase isolated from the CNS of Manduca sexta that is inhibited by calcium" Journal of Neurochemistry January 2003
  • "Soluble guanylyl cyclases in invertebrates" Advances in Experimental Biology  2007
  • "Nicotinic-acetylcholine receptors are functionally coupled to the nitric oxide/cGMP-pathway in insect neurons" Journal of Neurochemistry October 2002
  • "Cyclic GMP regulation and function in insects" Advances in Insect Physiology  2002
  • "Substrate phosphoprotein availability regulates eclosion hormone sensitivity in an insect CNS" Nature  1986
  • "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 October 10 2014
  • "The action of formamidines on octopamine receptors in the locust" Pesticide Biochemistry and Physiology  1985
  • "Invertebrates yield a plethora of atypical guanylyl cyclases" Molecular Neurobiology April 2004
  • "Eclosion hormone stimulates cyclic GMP levels in Manduca sexta nervous tissue via arachidonic acid metabolism with little or no contribution from the production of nitric oxide" Journal of Neurochemistry October 1992
  • "Phosphodiesterase-8A binds to and regulates Raf-1 kinase" Proceedings of the National Academy of Sciences of the United States of America April 16 2013
  • "Eclosion hormone action on the nervous system. Intracellular messengers and sites of action" Annals of the New York Academy of Sciences  1997
  • "Drosophila gustatory preference behaviors require the atypical soluble guanylyl cyclases" Journal of Comparative Physiology A: Neuroethology, Sensory, Neural, and Behavioral Physiology July 2011
  • "Comparison of the expression patterns of five developmentally regulated genes in Manduca sexta and their regulation by 20-hydroxyecdysone in vitro" Journal of Experimental Biology July 1996
  • "The eclosion hormone system" Progress in Clinical and Biological Research  1990
  • "Response properties of visual neurons in the turtle nucleus isthmi" Journal of Comparative Physiology A: Neuroethology, Sensory, Neural, and Behavioral Physiology  2011
  • "The EGPs" Journal of Neuroscience  1988

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