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Senior Investigator

Susan Wray, Ph.D.

Cellular and Developmental Neurobiology Section

Porter Neuroscience Research Center
Building 35 Room 3A-1012
35 Convent Drive MSC 3703
Bethesda MD 20892-3703
Office: (301) 496-6646
Lab: (301) 496-8129
Fax: (301) 496-8578

Dr. Wray received her B.A. degree from Middlebury College and her M.S, and Ph.D. degrees from University of Rochester School of Medicine & Dentistry where she worked on development of neuroendocrine systems associated with puberty. She continued her work on neuroendocrine systems as a postdoctoral fellow with Harold Gainer in NICHD. In 1992 she became a faculty member of NINDS as a Unit Chief in the Laboratory of Neurochemistry and in 1999 became Chief of the newly created Cellular and Developmental Neurobiology Section. She is a council member of the International Society of Neuroendocrinology and a founding member of the American Neuroendocrine Society. Dr. Wray's laboratory is studying developmental cues underlying neuronal migration, and neurogenesis and regulation of neuroendocrine cells essential for reproduction.

Research focus of Cellular and Developmental Neurobiology Section: CDNS conducts fundamental research on neurogenesis of placodally derived neurons and the system dynamics of these cells which allow them to exhibit synchronized behavior. Our focus is on development and regulation of GnRH neurons, cells essential for reproduction. GnRH neurons originate in the nasal placode and during prenatal development migrate into the brain. Once within the brain, GnRH neurons become integral components of the hypothalamic-pituitary-gonadal axis and exhibit pulses of GnRH secretion in reproductively mature animals. Alterations in normal development or regulation of the GnRH system results in reproductive dysfunctions, as is seen in patients with Kallman Syndrome.

Our research addresses critical neurobiological issues such as phenotypic commitment and mechanisms involved in neuronal migration. Projects focus on craniofacial development, differentiation and migration of GnRH cells, and olfactory axon outgrowth. This system is a model for neurons exhibiting axophilic migration. Research includes: 1) signals for proper craniofacial development, 2) guidance factors that modulate neuronal migration and 3) intracellular signaling controlling cell movement and corresponding changes in cytoskeletal elements. In addition, the mechanisms regulating GnRH neuronal activity, including peptide secretion are being examined to decipher the cellular characteristics underlying neuroendocrine function and pulsatile secretion. We take advantage of the physiology of the GnRH system by examining the molecular and cellular properties of GnRH neuronal activity at different developmental, metabolic and/or reproductive states.

Research models include nasal explants, slice cultures, immortalized GnRH cell lines, and normal, cre/lox and transgenic mice. Approaches include videomicroscopy, calcium imaging, electrophysiology, immunocytochemistry, in situ histochemistry, single-cell PCR, and subtractive cDNA screening. Together, these models and approaches are used to manipulate the GnRH system.

Spontaneous Calcium Transients in a Migrating GnRH Neuron

Spontaneous calcium transients in a migrating GnRH neuron. This example of endogenous calcium spiking is from a GnRH neuron migrating away from the midline cartilage in a nasal explant. Warmer colors indicate higher concentrations of calcium. Elapsed time, 26 minutes. This cell is from Figure 1 in Hutchins B.I., Klenke, U. and Wray S. (2013). Calcium release-dependent actin flow in the leading process mediates axophilic migration. Journal of Neuroscience.

Download GnRH Calcium Video

Staff Image
  • Keenan Bartlett, B.S.
    Post baccalaureate Fellow

  • Hyunju Cho, Ph.D.
    Postdoctoral Fellow

  • Stephanie Constantin, Ph.D.
    Contract Scientist

  • Stephen Farmer, M.S.
    Post baccalaureate Fellow

  • Dakota Jacobs, M.A.
    Post baccalaureate Fellow

  • Katherine Pizano, B.A.
    Post baccalaureate Fellow

  • Daniel Reynolds, B.A.
    Pre-doctoral IRTA

  • Aybike Saglam, B.S.
    Graduate Student

  • Yufei Shan, Ph.D.
    Postdoctoral Fellow

  • Niteace Whittington, Ph.D.
    Postdoctoral Fellow

  • 1) Shan Y, Farmer SM, Wray S. (2021)
  • Drebrin regulates cytoskeleton dynamics in migrating neurons through interaction with CXCR4.
  • Proc Natl Acad Sci U S A. Jan 19;118(3):e2009493118. doi: 10.1073/pnas.2009493118.PMID: 33414275
  • 2) Constantin S, Reynolds D, Oh A, Pizano K, Wray S. (2021)
  • Nitric oxide resets kisspeptin-excited GnRH neurons via PIP2 replenishment.
  • Proc Natl Acad Sci U S A. Jan 5;118(1):e2012339118. doi: 10.1073/pnas.2012339118.PMID: 33443156
  • 3) Saglam A, Calof AL, Wray S. (2020).
  • Novel factor in olfactory ensheathing cell-astrocyte crosstalk: Anti-inflammatory protein α-crystallin B.
  • Glia. Dec 12. doi: 10.1002/glia.23946. PMID: 33314354
  • 4) Shan Y, Saadi H, Wray S. (2020)
  • Heterogeneous Origin of Gonadotropin Releasing Hormone-1 Neurons in Mouse Embryos Detected by Islet-1/2 Expression.
  • Front Cell Dev Biol. 8: 35. PMCID:PMC7002318
  • 5) Cho HJ, Shan Y, Whittington NC, Wray S. (2019)
  • Nasal Placode Development, GnRH Neuronal Migration and Kallmann Syndrome.
  • Front Cell Dev Biol. 7:121.
  • 6) Saadi H, Shan Y, Marazziti D, Wray S (2019)
  • GPR37 signaling modulates migration of olfactory ensheathing cells and gonadotropin releasing hormone cells in mice
  • Frontiers Cellular Neuroscience
  • 7) Constantin S, Wray S (2018)
  • Nociceptin/Orphanin-FQ inhibits gonadotropin releasing hormone neurons via G-protein gated inwardly rectifying potassium channels
  • eNeuro, 26, 5(6)
  • 8) Dairaghi L, Flannery E, Giacobini P, Saglam A, Saadi H, Constantin S, Casoni F, Howell BW, Wray S (2018)
  • Reelin can modulate migration of olfactory ensheathing cells and gonadotropin releasing hormone neurons via the canonical pathway
  • Frontiers in Cellular Neuroscience, 12, 228
  • 9) Turan I, Hutchins BI, Hacihamdioglu B, Kotan LD, Gurbuz F, Ulubay A, Mengen E, Yuksel B, Wray S, Topaloglu AK (2017)
  • CCDC141 Mutations in Idiopathic Hypogonadotropic Hypogonadism
  • JCEM, 102, 1816-1825
  • 10) Constantin S, Wray S (2016)
  • Galanin activates G protein gated inwardly rectifying potassium channels and suppresses kisspeptin-10 activation of GnRH neurons
  • Endocrinology, 157, 3197-212
  • 11) Hutchins BI, Kotan LD, Taylor-Burds C, Ozkan Y, Cheng PJ, Gurbuz F, Tiong JDR, Mengen E, Yuksel B, Topaloglu AK, Wray S (2016)
  • CCDC141 Mutation identified in Anosmic Hypogonadotropic Hypogonadism (Kallmann Syndrome) alters GnRH neuronal migration
  • Endocrinology, 157, 1956-66
  • 12) Klenke U, Constantin S, Wray S (2016)
  • BPA directly decreases GnRH neuronal activity via non-canonical pathway
  • Endocrinology, 157, 1980-90
  • 13) Taylor-Burds C, Cheng P, Wray S (2015)
  • Chloride accumulators NKCC1 and AE2 in mouse GnRH neurons: Implications for GABAA mediated excitation
  • Plosone, 25, 0(6): e0131076
  • 14) Hutchins BI, Wray S (2014)
  • Capture of microtubule plus-ends at the actin cortex promotes axophilic neuronal migration by enhancing microtubule tension in the leading process
  • Frontiers in Cellular Neuroscience, 8, 400
  • 15) Kotan LD*, Hutchins BI*, Ozkan Y, Demirel F, Stoner H, Cheng PJ, Esen I, Gurbuz F, Y. Bicakci K, Mengen E, Yuksel B, Wray S, Topaloglu AK (2014)
  • Mutations in FEZF1 Cause Kallmann Syndrome
  • American Journal of Human Genetics, 4;95(3), 326-31
  • 16) Klenke U, Taylor-Burds C, Wray S (2014)
  • Metabolic influences on reproduction: Adiponectin attenuates gonadotropin-releasing hormone-1 neuronal activity
  • Endocrinology, 155(5), 1851-63
  • 17) Hutchins BI, Klenke U, Wray S (2013)
  • Calcium release-dependent actin flow in the leading process mediates axophilic migration
  • J. Neuroscience, 33, 11361-71
  • 18) Forni PE, Bharti K, Flannery E, Shimogori T, Wray S (2013)
  • The indirect role of FGF8 in defining neurogenic niches of the olfactory/GnRH systems.
  • J. Neuroscience, 33, 19620-19634
  • 19) Forni, PE, Wray, S (2012)
  • Neural Crest and olfactory system: new prospective and controversies
  • Molecular Neurobiology
  • 20) Casoni F, Hutchins BI, Donohue D, Fornaro M, Condie BG, Wray S (2012)
  • SDF and GABA Interact to Regulate Axophilic Migration of GnRH-1 Neurons
  • Journal of Cell Science
  • 21) Bashour N, Wray S (2012)
  • Progesterone directly and rapidly inhibits GnRH neuronal activity via progesterone receptor membrane component 1
  • Endocrinology
  • 22) Forni P, Fornaro M, Guenette S, Wray S (2011)
  • A role for Fe65 in controlling GnRH-1 neurogenesis
  • J. Neuroscience
  • 23) Forni PE, Taylor-Burds C, Melvin S, Williams T, Wray S (2011)
  • Neural Crest and Ectodermal Cells Intermix in the Nasal Placode to give rise to GnRH-1 Neurons, Sensory Neurons and Olfactory Ensheathing Cells
  • J. Neuroscience
  • 25) Wray, S (2010)
  • Nose to Brain: Development of Gonadotrophin-Releasing Hormone -1 Neurones
  • J. Neuroendocrinology
  • 26) Klenke U, Constantin S, Wray S (2010)
  • Neuropeptide Y directly inhibits neuronal activity in a subpopulation of GnRH-1 neurons via Y1 receptors
  • Endocrinology
  • 27) Metz H, Wray S (2010)
  • Use of mutant mouse lines to Investigate origin of GnRH-1 neurons: lineage independent of the adenohypophysis
  • Endocrinology
  • 28) Constantin S, Klenke U, Wray S (2010)
  • The calcium oscillator of GnRH-1 neurons is developmentally regulated
  • Endocrinology
  • 29) Constantin S, Caraty A, Wray S, Duittoz A (2009)
  • Development of GnRH-1 secretion in mouse nasal explants
  • Endocrinology
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