Colorado PROFILES, The Colorado Clinical and Translational Sciences Institute (CCTSI)
Keywords
Last Name
Institution

Contact Us
If you have any questions or feedback please contact us.

Xiaoqiao Xie

TitleAsst Professor-Research
InstitutionUniversity of Colorado Denver - Anschutz Medical Campus
DepartmentSOM-SRG
Email

    Collapse Biography 
    Collapse education and training
    University of North Carolina at Chapel Hill, Chapel Hill, NCPost-doctoral08/2016Pharmacology and Glia Biology
    University of California, Riverside, Riverside, CAPh. D.08/2011Neuroscience and astrocyte physiology
    University of Science and Technology of China, Hefei, Anhui, ChinaM. S.07/2005Biophysics and Neuroscience
    University of Science and Technology of China, Hefei, Anhui, ChinaB. S.07/2002Biophysics
    Collapse awards and honors
    2011University Teaching Certificate, University of California, Riverside
    2014Excellence in Mentoring Undergraduates, University of North Carolina at Chapel Hill
    2016Training award, Federation of American Societies for Experimental Biology/Maximizing Access to Research Careers
    2023Young Investigator Award, The Society for Basic Urologic Research (SBUR)
    2023Early-career Faculty Research Development Award, Ludeman Center for Women's Health Research
    2024Faculty Professionalism Award, Department of surgery, School of Medicine, CU-AMC

    Collapse Overview 
    Collapse overview
    As a glia biologist, I am interested in the neuromodulatory role of peripheral glial fibrillary acidic protein-expressing (GFAP+) glia in micturition and their therapeutic potential in benign bladder disorder. The Xie lab works in close collaboration with other research labs in the Basic and Translational Urology Research Program in the Division of Urology, Department of Surgery.

    Research project 1. The analgesic role of sensory satellite glial cells in bladder overactivity and chronic pelvic pain
    Patients with urological chronic pelvic pain syndrome (UCPPS) experience chronic pelvic pain (CPP) and lower urinary tract symptoms (LUTS). The UCPPS symptoms are closely associated with nociceptive sensitization in the nervous system, which underlies visceral allodynia and hyperalgesia. Previous studies suggested that afferent hypersensitivity in bladder-projecting sensory neurons plays an important role in the generation and the maintenance of UCPPS symptoms, especially bladder pain and urinary frequency. We have identified that satellite glial activation in lumbosacral sensory ganglia alleviates inflammatory pain in mice. In addition, terminal Schwann cell signaling also contribute to nerve injury-induced neuropathic pain. These data suggested the strong therapeutic potential of peripheral GFAP+ glial signaling in acute control of afferent excitability.
    Our fundings suggest that Gq-GPCR activation in peripheral GFAP+ glia might be a promising and highly innovative approach to alleviate the symptoms of bladder overactivity and pain. The current work focuses on 1) developing experimental approaches for targeted activation of Gq-GPCR signaling pathways in sensory SGCs; 2) assessing the changes in lumbosacral bladder afferent sensitivity following glial Gq-GPCR activation; and 3) evaluating the glial activation-induced changes in LUTS and visceral hypersensitivity in vivo and in mouse models of UCPPS. Gq-coupled Designer Receptors Exclusively Activated by Designer Drugs (Gq-DREADD) is used to selectively activate Gq-GPCR signaling cascades in lumbosacral sensory SGCs via targeted adeno-associated virus (AAV) delivery. Afferent sensitivity and bladder functions are evaluated in vivo by well-established and clinically relevant visceral nociceptive assays and urodynamic assays. This project aims to characterize the role of SGC Gq-GPCR signaling in regulating visceral nociception in vivo as well as test its therapeutic potential to reverse pain and voiding dysfunction in UCPPS patients.
    Relevant publications:
    Xie AX, Pan XQ, Meacham RB, Malykhina AP. (2018) The Expression of Transcription Factors MeCP2 and CREB Is Modulated in Inflammatory Pelvic Pain. Front Syst Neurosci. 2019 Jan 11;12:69. doi: 10.3389/fnsys.2018.00069. eCollection 2018.
    Xie AX*, Madayag A, Minton SK, McCarthy KD, Malykhina AP. (2020) Sensory satellite glial Gq-GPCR activation alleviates inflammatory pain via peripheral adenosine 1 receptor activation. *Corresponding author. Sci Rep. 2020 Aug 25;10(1):14181. doi: 10.1038/s41598-020-71073-z.
    Xie AX†*, Taves S†, McCarthy KD. (2021) Nuclear factor Kappa B-COX2 pathway activation in non-myelinating Schwann cells is necessary for the maintenance of neuropathic pain in mice. *Corresponding author. Front. Cell. Neurosci. 14 January 2022 doi: 10.3389/fncel.2021.782275
    Xie AX, Iguchi N, Clarkson TC, Malykhina AP. (2022) Pharmacogenetic inhibition of sensory afferent excitability alleviates bladder VEGF signaling-induced visceral hypersensitivity in an animal model of UCPPS. PLOS ONE, in press.
    Xie AX†, Iguchi N†, Malykhina AP*. Long-term follow-up of TREK-1 KO mice reveals the development of bladder hypertrophy and impaired bladder smooth muscle contractility with age. in Review
    Yesupatham SK, Malykhina AP, Xie AX*. Transcriptome Analysis in Lumbosacral Dorsal Root Ganglia Suggests Sex-specific Mechanisms Underlying Visceral Hypersensitivity. In Review

    Research project 2. The neuroactive role of autonomic satellite glial cells in modulating bladder physiology
    The long-term goal of conducting glia research is to target glial signaling for disease treatments. But first, we need to understand the role of glia in vivo and in intact neural circuits. We have shown that pharmacogenetic activation of Gq-GPCR signaling in sympathetic SGCs in superior cervical ganglia significantly increases heart rate, cardio output, and blood pressure. Moreover, persist activation of sympathetic SGCs results in hypotension in sex-dependent manner. Our finding was the first report on the role of SGCs in autonomic ganglia. Current research in the Xie lab aims to reveal the molecular mechanisms underlying the neuroactive effect of satellite glia-neuron interactions in the sympathetic ganglia. In addition, we are actively testing the hypothesis that Gq-GPCR activation in SGCs in the major pelvic ganglia, the autonomic ganglia innervating the urinary bladder will potentiate autonomic-driven bladder contractions and changes in micturition.
    Relevant publications:
    Agulhon C, Boyt KM, Xie AX, Friocourt F, Roth BL, McCarthy KD. (2013) Modulation of the autonomic nervous system and behaviour by acute glial cell Gq protein-coupled receptor activation in vivo. J Physiol. 2013 Nov 15;591(22):5599-609. doi: 10.1113/jphysiol.2013.261289.
    Xie AX, Petravicz, J, McCarthy KD. (2015) Molecular approaches for manipulating astrocytic signaling in vivo. Front Cell Neurosci. 2015 Apr 21;9:144. doi: 10.3389/fncel.2015.00144
    Xie AX*, Lee JJ, McCarthy KD. (2016) Ganglionic GFAP+ Glial Gq-GPCR Signaling Enhances Heart Functions in vivo. *Corresponding author. JCI Insight. 2017;2(2):e90565. doi:10.1172/jci.insight.90565.
    Xie AX*, Chaia A, McCarthy KD. (2017) Targeting sympathetic glia for treating cardiovascular diseases. *Corresponding author. Receptors and Clinical Investigation. 2017;4:e1572. doi: 10.14800/rci.1572.

    Collapse Research 
    Collapse research activities and funding
    Translational Methods (TM) Pilot Award     (Alison Xiaoqiao Xie and Sarah Calve)Aug 1, 2024 - Jul 31, 2025
    Colorado Clinical and Translational Sciences Institute
    Development of a murine pelvic ganglia-bladder preparation for the study of glial control of micturition
    Role: Co-PI

    Early-career Faculty Research Development Award     (Alison Xiaoqiao Xie)Sep 1, 2023 - Aug 31, 2024
    Ludeman Center for Women's Health Research
    Sex differences in sympathetic glial regulation of blood pressure
    Role: PI

    R01 DK129260-01     (Alison Xiaoqiao Xie)Aug 5, 2021 - Aug 4, 2026
    NIH/NIDDK
    Activating Peripheral Glia to Relieve Visceral Pain in Animal Models of Urological Chronic Pelvic Pain Syndrome (UCPPS)
    Role: PI

    Surgery-AEF-Xie     (Alison Xiaoqiao Xie)Sep 1, 2020 - Aug 31, 2021
    Department of Surgery, Academic Enrichment Funds
    The role of mechanosensitive TREK-1 channels in detrusor overactivity and voiding dysfunction in patients with overactive bladder (OAB)
    Role: PI

    CO-M-19-7     (Alison Xiaoqiao Xie)Mar 1, 2019 - Feb 29, 2020
    Colorado Clinical and Translational Sciences Institute (CCTSI), CO-Pilot Grant
    Beyond the neurons: the role of peripheral glia in neurogenic bladder dysfunction
    Role: PI

    Collapse Bibliographic 
    Collapse 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.
    List All   |   Timeline
    1. Xie AX, Iguchi N, Malykhina AP. Long-term follow-up of TREK-1 KO mice reveals the development of bladder hypertrophy and impaired bladder smooth muscle contractility with age. Am J Physiol Renal Physiol. 2024 Jun 01; 326(6):F957-F970. PMID: 38601986.
      View in: PubMed
    2. Clarkson TC, Iguchi N, Xie AX, Malykhina AP. Differential transcriptomic changes in the central nervous system and urinary bladders of mice infected with a coronavirus. PLoS One. 2022; 17(12):e0278918. PMID: 36490282.
      View in: PubMed
    3. Xie AX, Iguchi N, Clarkson TC, Malykhina AP. Pharmacogenetic inhibition of lumbosacral sensory neurons alleviates visceral hypersensitivity in a mouse model of chronic pelvic pain. PLoS One. 2022; 17(1):e0262769. PMID: 35077502.
      View in: PubMed
    4. Xie AX*, Taves S, McCarthy KD. *Corresponding author. Nuclear factor Kappa B-COX2 pathway activation in non-myelinating Schwann cells is necessary for the maintenance of neuropathic pain in mice. Front Cell Neurosci. 2022; (15):782275.
    5. Iguchi N, Carrasco A, Xie AX, Pineda RH, Malykhina AP, Wilcox DT. Functional constipation induces bladder overactivity associated with upregulations of Htr2 and Trpv2 pathways. Sci Rep. 2021 01 13; 11(1):1149. PMID: 33441874.
      View in: PubMed
    6. Xie AX*, Madayag A, Minton SK, McCarthy KD, Malykhina AP. *Corresponding author. Sensory satellite glial Gq-GPCR activation alleviates inflammatory pain via peripheral adenosine 1 receptor activation. Sci Rep. 2020; 1(10):14181.
    7. Xie AX, Pan XQ, Meacham RB, Malykhina AP. The Expression of Transcription Factors Mecp2 and CREB Is Modulated in Inflammatory Pelvic Pain. Front Syst Neurosci. 2018; 12:69. PMID: 30687029.
      View in: PubMed
    8. Xie AX*, Chaia AI, McCarthy KD. * Corresponding author. Receptors & Clinical Investigation. Targeting sympathetic glia for treating cardiovascular diseases. 2017; (4):e1572.
    9. Xie AX, Lee JJ, McCarthy KD. Ganglionic GFAP + glial Gq-GPCR signaling enhances heart functions in vivo. JCI Insight. 2017 01 26; 2(2):e90565. PMID: 28138563.
      View in: PubMed
    10. Annis RP, Swahari V, Nakamura A, Xie AX, Hammond SM, Deshmukh M. Mature neurons dynamically restrict apoptosis via redundant premitochondrial brakes. FEBS J. 2016 12; 283(24):4569-4582. PMID: 27797453.
      View in: PubMed
    11. Xie AX, Petravicz J, McCarthy KD. Molecular approaches for manipulating astrocytic signaling in vivo. Front Cell Neurosci. 2015; 9:144. PMID: 25941472.
      View in: PubMed
    12. Xie AX, Lauderdale K, Murphy T, Myers TL, Fiacco TA. Inducing plasticity of astrocytic receptors by manipulation of neuronal firing rates. J Vis Exp. 2014 Mar 20; (85). PMID: 24686723.
      View in: PubMed
    13. Sun MY, Devaraju P, Xie AX, Holman I, Samones E, Murphy TR, Fiacco TA. Astrocyte calcium microdomains are inhibited by bafilomycin A1 and cannot be replicated by low-level Schaffer collateral stimulation in situ. Cell Calcium. 2014 Jan; 55(1):1-16. PMID: 24262208.
      View in: PubMed
    14. Agulhon C, Boyt KM, Xie AX, Friocourt F, Roth BL, McCarthy KD. Modulation of the autonomic nervous system and behaviour by acute glial cell Gq protein-coupled receptor activation in vivo. J Physiol. 2013 Nov 15; 591(22):5599-609. PMID: 24042499.
      View in: PubMed
    15. Xie AX, Sun MY, Murphy T, Lauderdale K, Tiglao E, Fiacco TA. Bidirectional scaling of astrocytic metabotropic glutamate receptor signaling following long-term changes in neuronal firing rates. PLoS One. 2012; 7(11):e49637. PMID: 23166735.
      View in: PubMed
    16. Carson MJ, Crane J, Xie AX. Modeling CNS microglia: the quest to identify predictive models. Drug Discov Today Dis Models. 2008; 5(1):19-25. PMID: 19444332.
      View in: PubMed
    17. Wang H, Xie X, Li X, Chen B, Zhou Y. Functional degradation of visual cortical cells in aged rats. Brain Res. 2006 Nov 29; 1122(1):93-8. PMID: 17010946.
      View in: PubMed
    18. Jia F, Wei H, Li X, Xie X, Zhou Y. Short-term synaptic plasticity in the rat geniculo-cortical pathway during development in vivo. Neurosci Lett. 2006 May 01; 398(1-2):73-7. PMID: 16406670.
      View in: PubMed
    19. Xie X, Wang H, Chen B, Zhou Y,. Neural Response Characteristic of Neuron to Flashing Stimulus in Visual Cortex of Young Rats. Progress in Biochemistry and Biophysics. 2005; 11(32):1088-1092.
    20. Jia F, Xie X, Zhou Y. Short-term depression of synaptic transmission from rat lateral geniculate nucleus to primary visual cortex in vivo. Brain Res. 2004 Mar 26; 1002(1-2):158-61. PMID: 14988046.
      View in: PubMed
    Xie's Networks
    Click the "See All" links for more information and interactive visualizations!
    Concepts Expand Description
    _
    Co-Authors Expand Description
    _
    Similar People Expand Description
    _
    Same Department Expand Description

    Copyright © 2024 The Regents of the University of Colorado, a body corporate. All rights reserved. (Harvard PROFILES RNS software version: 2.11.1)