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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

    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.

    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
    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, Clarkson TC, Malykhina AP. Pharmacogenetic inhibition of sensory afferent excitability alleviates bladder VEGF signaling-induced visceral hypersensitivity in an animal model of UCPPS. PLOS ONE, In press. 2022.
    2. 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.
    3. 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
    4. Xie AX, Madayag A, Minton SK, McCarthy KD, Malykhina AP. Sensory satellite glial Gq-GPCR activation alleviates inflammatory pain via peripheral adenosine 1 receptor activation. Sci Rep. 2020 08 25; 10(1):14181. PMID: 32843670.
      View in: PubMed
    5. 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
    6. Xie AX, Chaia AI, McCarthy KD. Receptors & Clinical Investigation. Targeting sympathetic glia for treating cardiovascular diseases. 2017; (4):e1572.
    7. 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
    8. 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
    9. 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
    10. 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
    11. 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
    12. 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
    13. 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
    14. 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
    15. 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
    16. 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
    17. 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
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