Alison Xie, PhD
Assistant Research Professor, Surgery-Urology

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Graduate Schools :
  • PhD, University of California, Riverside (2011)
  • MS, University of Science and Technology of China (2005)
Undergraduate School:
  • BS, University of Science and Technology of China (2002)
Languages: English, Mandarin
Department: Surgery-Urology

Professional Titles

  • Assistant Professor

Recognition & Awards

  • Training award, the Federation of American Societies for Experimental Biology/Maximizing Access to Research Careers Program (2016)
  • Excellence in Mentoring Undergraduates, University of North Carolina at Chapel Hill (2014)
  • University Teaching Certificate, University of California, Riverside (2011)

Research Interests

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. 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. 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 findings 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. 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.

Publications

  • 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. PubMed PMID: 35077502
  • 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
  • Xie AX†*, Taves S†, McCarthy KD. 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., 14 January 2022, https://doi.org/10.3389/fncel.2021.782275.
  • Iguchi N, Carrasco A Jr, Xie AX, Pineda RH, Malykhina AP, Wilcox DT. Functional constipation induces bladder overactivity associated with upregulations of Htr2 and Trpv2 pathways. Sci Rep. 2021 Jan 13;11(1):1149. PubMed PMID: 33441874
  • 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 Aug 25;10(1):14181. PubMed PMID: 32843670
  • 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. PubMed PMID: 30687029
  • Xie AX*, Lee JJ, McCarthy KD. Ganglionic GFAP+ glial Gq-GPCR signaling enhances heart functions in vivo. JCI Insight. 2017 Jan 26;2(2):e90565. PubMed PMID: 28138563
  • Xie AX*, Chaia A, McCarthy KD. Targeting sympathetic glia for treating cardiovascular diseases. Receptors &Clinical Investigation 2017; 4: e1572. doi: 10.14800/rci.1572;
  • Annis RP, Swahari V, Nakamura A, Xie AX, Hammond SM, Deshmukh M. Mature neurons dynamically restrict apoptosis via redundant premitochondrial brakes. FEBS J. 2016 Dec;283(24):4569-4582. PubMed PMID: 27797453
  • Xie AX, Petravicz J, McCarthy KD. Molecular approaches for manipulating astrocytic signaling in vivo. Front Cell Neurosci. 2015;9:144. PubMed PMID: 25941472
  • 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. PubMed PMID: 24262208
  • 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). PubMed PMID: 24686723
  • 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. PubMed PMID: 24042499
  • 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. PubMed PMID: 23166735
  • 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. PubMed PMID: 19444332
  • 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. PubMed PMID: 17010946
  • 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 1;398(1-2):73-7. PubMed PMID: 16406670
  • 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. PubMed PMID: 14988046
  • Sensory Glia Gq-GPCR Activation In Vivo Modulates Micturition Functions in an Animal Model of Chronic Pelvic Pain
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Professional Memberships

  • South-Central Section of the American Urological Association, Faculty member
  • Society for Basic Urologic Research, Faculty member
  • American Society of Neurochemistry, Faculty member
  • Colorado Clinical Translational Science Institute, Faculty member
  • Center for NeuroScience, CU-AMC, Faculty member
  • Neuroscience Graduate Program, CU-AMC, Faculty member
Volunteer Activities
Scientific reviewer for the Colorado Clinical and Translational Sciences Institute (CCTSI) Judge for the Denver Metro Regional Science and Engineering Fair

Public Speaking
Yes
Neural control of cardiovascular function and bladder functions; cell-cell interactions in the nervous system; glial function and neuromodulation; GPCR signaling in glial cells.

General Information

Graduate Schools:
  • PhD, University of California, Riverside (2011)
  • MS, University of Science and Technology of China (2005)
Undergraduate Schools:
  • BS, University of Science and Technology of China (2002)
Languages: English, Mandarin
Department: Surgery-Urology
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CU Resources
Contact Us
CU Anschutz
Fitzsimons Building
13001 East 17th Place
Campus Box C290
Aurora, CO 80045

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