Joao Braz, PhD

Title(s)ASSOC RES-FY, Anatomy
SchoolSchool of Medicine
Address1550 Fourth St, #345
San Francisco CA 94158
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    Collapse Biography 
    Collapse Education and Training
    University of Paris VI, Paris, FrancePhD01/2000Molecular and cellular biology (Pain)
    University of Paris VI, Paris, FranceMasters1996Molecular and cellular biology

    Collapse Overview 
    Collapse Overview
    My research focuses on the transmission and control of "pain " messages. I have been studying the neuronal circuits that underlie the production of pain, combining several approaches that range from cellular and molecular biology to virology, pharmacology and behavior. In order to dissect the nociceptive circuitry, I developed a novel genetic approach (ZW transgenic mouse) that uses transneuronal transport of the anterograde tracer, wheat germ agglutinin (WGA) to study the central circuits that arise from primary afferent pain fibers and how they are modified after tissue or nerve injury. The key feature of the transgene that I have engineered is that the expression of the tracer can be controlled both spatially and temporally. Paralleling these studies, I also developed a new viral approach to study the inputs of anatomically distinct spinal cord nociceptive projection neurons. This approach involves the targeting of the expression of a virally-driven Cre recombinase to projection neurons so as to control the neuronal populations in which the replication of a Cre-dependent viral vector (pseudorabies) is subsequently triggered. In my effort to study the circuits engaged by DRG neurons, I've also participated in the generation of reporter mice (knock-ins, BAC transgenics, CRISPR) that allow a clearer picture of the distribution of subsets of primary afferent nociceptors and nociceptive projection neurons. I’ve also used transplantation of inhibitory precursor cells into the spinal cord to treat various models of chronic pain and chronic itch. I showed that these cells differentiate into GABAergic interneurons and integrate remarkably well into local spinal cord circuitry. I have also shown also that these cells are able to completely reverse the mechanical hypersensitivity that is produced by a peripheral nerve injury and significantly reduce spontaneous scratching and the severity of skin lesions in a model of chronic itch.
    In collaboration with a graduate student in the lab, we molecularly profiled spinal cord projection neurons in order to better understand how different modalities of pain and itch are transmitted to the brain.
    More recently, I started characterizing the distribution and expression of so-called "dark genes" (genes that are understudied in the "pain" field) in the DRG and spinal cord in order to identify novel targets for pain and itch. Among those genes, we are particularly interested in investigating the contribution of several ion channels in pain processing, namely Cacna2d1, 2d2, 2d3 and 2d4; Tmc3, 4, 5 and 7 as well as Qrfpr. For this, we characterize the behavioral consequences of knocking down the expression of each of these ion channels. I am also contributing to a project that focuses on developing new and promising pharmocological compounds for pain relief. This is a vast collaboration with both UCSF and non-UCSF laboratories that is funded by the Department of Defense. This project will provide several new drugs that inhibit known "pain receptors" and exhibit higher analgesic efficacy and lower side effects profiles than what is currently available. My role is to supervise the "in vivo" team that characterizes the analgesic properties of the compounds in rodents, in the setting of both acute and chronic pain. Among those targets, we are particularly interested in the alpha-2A adrenergic receptor, for which we have developed and characterized a novel agonist that exhibits strong analgesic anti-allodynic effects but is devoid of the sedative effects that characterize many of the alpha 2A drugs. Other targets that are under investigating include the receptors for sigma 2, cannabinoid 1, prostaglandin 1 and 4, serotonin transporter and mu opioid receptors. I have generated conditional knock-out mice for all these genes so that we can selectively knock down their expression in the DRG and spinal cord.

    Collapse Research 
    Collapse Research Activities and Funding
    Spinal Cord Transplants of GABAergic Precursor Cells to Treat Chronic Pain
    NIH R01NS078326Sep 28, 2012 - Jun 30, 2017
    Role: Principal Investigator

    Collapse Bibliographic 
    Collapse Publications
    Publications listed below are automatically derived from MEDLINE/PubMed and other sources, which might result in incorrect or missing publications. Researchers can login to make corrections and additions, or contact us for help. to make corrections and additions.
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    1. Large library docking for cannabinoid-1 receptor agonists with reduced side effects. bioRxiv. 2024 Feb 28. Tummino TA, Iliopoulos-Tsoutsouvas C, Braz JM, O'Brien ES, Stein RM, Craik V, Tran NK, Ganapathy S, Liu F, Shiimura Y, Tong F, Ho TC, Radchenko DS, Moroz YS, Rosado SR, Bhardwaj K, Benitez J, Liu Y, Kandasamy H, Normand C, Semache M, Sabbagh L, Glenn I, Irwin JJ, Kumar KK, Makriyannis A, Basbaum AI, Shoichet BK. PMID: 38328157; PMCID: PMC10849508.
      View in: PubMed   Mentions:
    2. Docking for EP4R antagonists active against inflammatory pain. Nat Commun. 2023 Dec 06; 14(1):8067. Gahbauer S, DeLeon C, Braz JM, Craik V, Kang HJ, Wan X, Huang XP, Billesbølle CB, Liu Y, Che T, Deshpande I, Jewell M, Fink EA, Kondratov IS, Moroz YS, Irwin JJ, Basbaum AI, Roth BL, Shoichet BK. PMID: 38057319; PMCID: PMC10700596.
      View in: PubMed   Mentions:    Fields:    Translation:HumansAnimals
    3. IL-31-dependent neurogenic inflammation restrains cutaneous type 2 immune response in allergic dermatitis. Sci Immunol. 2023 10 20; 8(88):eabi6887. Fassett MS, Braz JM, Castellanos CA, Salvatierra JJ, Sadeghi M, Yu X, Schroeder AW, Caston J, Munoz-Sandoval P, Roy S, Lazarevsky S, Mar DJ, Zhou CJ, Shin JS, Basbaum AI, Ansel KM. PMID: 37831760; PMCID: PMC10890830.
      View in: PubMed   Mentions:    Fields:    Translation:Animals
    4. Pain and Itch Processing in Aged Mice. J Pain. 2024 Jan; 25(1):53-63. Braz JM, Hamel K, Craik V, Rodriguez-Rosado S, Bhardwaj K, Jewell M, Bieri G, Villeda SA, Basbaum AI. PMID: 37482234.
      View in: PubMed   Mentions:    Fields:    Translation:Animals
    5. Structure-based discovery of conformationally selective inhibitors of the serotonin transporter. Cell. 2023 05 11; 186(10):2160-2175.e17. Singh I, Seth A, Billesbølle CB, Braz J, Rodriguiz RM, Roy K, Bekele B, Craik V, Huang XP, Boytsov D, Pogorelov VM, Lak P, O'Donnell H, Sandtner W, Irwin JJ, Roth BL, Basbaum AI, Wetsel WC, Manglik A, Shoichet BK, Rudnick G. PMID: 37137306; PMCID: PMC10306110.
      View in: PubMed   Mentions: 8     Fields:    Translation:AnimalsCells
    6. Paradoxical increases in anterior cingulate cortex activity during nitrous oxide-induced analgesia reveal a signature of pain affect. bioRxiv. 2023 Apr 03. Weinrich JA, Liu CD, Jewell ME, Andolina CR, Bernstein MX, Benitez J, Rodriguez-Rosado S, Braz JM, Maze M, Nemenov MI, Basbaum AI. PMID: 37066151; PMCID: PMC10104003.
      View in: PubMed   Mentions:
    7. Structure-based discovery of nonopioid analgesics acting through the α2A-adrenergic receptor. Science. 2022 09 30; 377(6614):eabn7065. Fink EA, Xu J, Hübner H, Braz JM, Seemann P, Avet C, Craik V, Weikert D, Schmidt MF, Webb CM, Tolmachova NA, Moroz YS, Huang XP, Kalyanaraman C, Gahbauer S, Chen G, Liu Z, Jacobson MP, Irwin JJ, Bouvier M, Du Y, Shoichet BK, Basbaum AI, Gmeiner P. PMID: 36173843; PMCID: PMC10360211.
      View in: PubMed   Mentions: 23     Fields:    Translation:HumansAnimals
    8. TRPV1 drugs alter core body temperature via central projections of primary afferent sensory neurons. Elife. 2022 08 15; 11. Yue WWS, Yuan L, Braz JM, Basbaum AI, Julius D. PMID: 35968676; PMCID: PMC9377796.
      View in: PubMed   Mentions: 6     Fields:    Translation:HumansAnimalsCells
    9. Intraspinal Transplantation of Precursors of Cortical GABAergic Interneurons to Treat Neuropathic Pain. . 2022 May 27; 178:159-170. Braz BJ, Basbaum BA. .
      View in: Publisher Site   Mentions:
    10. ACVR1-activating mutation causes neuropathic pain and sensory neuron hyperexcitability in humans. Pain. 2023 01 01; 164(1):43-58. Yu X, Ton AN, Niu Z, Morales BM, Chen J, Braz J, Lai MH, Barruet E, Liu H, Cheung K, Ali S, Chan T, Bigay K, Ho J, Nikolli I, Hansberry S, Wentworth K, Kriegstein A, Basbaum A, Hsiao EC. PMID: 35442931; PMCID: PMC9582048.
      View in: PubMed   Mentions: 3     Fields:    Translation:HumansCells
    11. Structure-Based Design of a Chemical Probe Set for the 5-HT5A Serotonin Receptor. J Med Chem. 2022 03 10; 65(5):4201-4217. Levit Kaplan A, Strachan RT, Braz JM, Craik V, Slocum S, Mangano T, Amabo V, O'Donnell H, Lak P, Basbaum AI, Roth BL, Shoichet BK. PMID: 35195401; PMCID: PMC9116900.
      View in: PubMed   Mentions: 7     Fields:    Translation:Humans
    12. Structures of the σ2 receptor enable docking for bioactive ligand discovery. Nature. 2021 Dec; 600(7890):759-764. Alon A, Lyu J, Braz JM, Tummino TA, Craik V, O'Meara MJ, Webb CM, Radchenko DS, Moroz YS, Huang XP, Liu Y, Roth BL, Irwin JJ, Basbaum AI, Shoichet BK, Kruse AC. PMID: 34880501; PMCID: PMC8867396.
      View in: PubMed   Mentions: 49     Fields:    Translation:Animals
    13. Regulatory T-cells inhibit microglia-induced pain hypersensitivity in female mice. Elife. 2021 10 15; 10. Kuhn JA, Vainchtein ID, Braz J, Hamel K, Bernstein M, Craik V, Dahlgren MW, Ortiz-Carpena J, Molofsky AB, Molofsky AV, Basbaum AI. PMID: 34652270; PMCID: PMC8639143.
      View in: PubMed   Mentions: 27     Fields:    Translation:AnimalsCells
    14. LB722 IL-31/IL31RA negatively regulate IL-4 production and cutaneous M2-like macrophage accumulation. Journal of Investigative Dermatology. 2021 Sep 1; 141(9):b5. Fassett FM, Braz BJ, Castellanos CC, Schroeder SA, Sadeghi SM, Mar MD, Zhou ZC, Shin SJ, Basbaum BA, Ansel AK. .
      View in: Publisher Site   Mentions:
    15. Pain and itch processing by subpopulations of molecularly diverse spinal and trigeminal projection neurons. Proc Natl Acad Sci U S A. 2021 07 13; 118(28). Wercberger R, Braz JM, Weinrich JA, Basbaum AI. PMID: 34234018; PMCID: PMC8285968.
      View in: PubMed   Mentions: 16     Fields:    Translation:AnimalsCells
    16. Contribution of dorsal horn CGRP-expressing interneurons to mechanical sensitivity. Elife. 2021 06 01; 10. Löken LS, Braz JM, Etlin A, Sadeghi M, Bernstein M, Jewell M, Steyert M, Kuhn J, Hamel K, Llewellyn-Smith IJ, Basbaum A. PMID: 34061020; PMCID: PMC8245130.
      View in: PubMed   Mentions: 12     Fields:    Translation:AnimalsCells
    17. Genetic priming of sensory neurons in mice that overexpress PAR2 enhances allergen responsiveness. Proc Natl Acad Sci U S A. 2021 02 23; 118(8). Braz JM, Dembo T, Charruyer A, Ghadially R, Fassett MS, Basbaum AI. PMID: 33602818; PMCID: PMC7923356.
      View in: PubMed   Mentions: 9     Fields:    Translation:AnimalsCells
    18. Dorsal root ganglion macrophages contribute to both the initiation and persistence of neuropathic pain. Nat Commun. 2020 01 14; 11(1):264. Yu X, Liu H, Hamel KA, Morvan MG, Yu S, Leff J, Guan Z, Braz JM, Basbaum AI. PMID: 31937758; PMCID: PMC6959328.
      View in: PubMed   Mentions: 162     Fields:    Translation:AnimalsCells
    19. Ablation of spinal cord estrogen receptor α-expressing interneurons reduces chemically induced modalities of pain and itch. J Comp Neurol. 2020 07; 528(10):1629-1643. Tran M, Braz JM, Hamel K, Kuhn J, Todd AJ, Basbaum AI. PMID: 31872868; PMCID: PMC7317200.
      View in: PubMed   Mentions: 4     Fields:    Translation:AnimalsCells
    20. GABAergic cell transplants in the anterior cingulate cortex reduce neuropathic pain aversiveness. Brain. 2019 09 01; 142(9):2655-2669. Juarez-Salinas DL, Braz JM, Etlin A, Gee S, Sohal V, Basbaum AI. PMID: 31321411; PMCID: PMC6752168.
      View in: PubMed   Mentions: 24     Fields:    Translation:AnimalsCells
    21. Microcircuit Mechanisms through which Mediodorsal Thalamic Input to Anterior Cingulate Cortex Exacerbates Pain-Related Aversion. Neuron. 2019 06 05; 102(5):944-959.e3. Meda KS, Patel T, Braz JM, Malik R, Turner ML, Seifikar H, Basbaum AI, Sohal VS. PMID: 31030955; PMCID: PMC6554049.
      View in: PubMed   Mentions: 56     Fields:    Translation:Animals
    22. Morphological and functional properties distinguish the substance P and gastrin-releasing peptide subsets of excitatory interneuron in the spinal cord dorsal horn. Pain. 2019 Feb; 160(2):442-462. Dickie AC, Bell AM, Iwagaki N, Polgár E, Gutierrez-Mecinas M, Kelly R, Lyon H, Turnbull K, West SJ, Etlin A, Braz J, Watanabe M, Bennett DLH, Basbaum AI, Riddell JS, Todd AJ. PMID: 30247267; PMCID: PMC6330098.
      View in: PubMed   Mentions: 37     Fields:    Translation:AnimalsCells
    23. Pain relief by supraspinal gabapentin requires descending noradrenergic inhibitory controls. Pain Rep. 2018 Jul-Aug; 3(4):e659. Juarez-Salinas DL, Braz JM, Hamel KA, Basbaum AI. PMID: 30123855; PMCID: PMC6085145.
      View in: PubMed   Mentions: 6  
    24. NaV1.1 inhibition can reduce visceral hypersensitivity. JCI Insight. 2018 06 07; 3(11). Salvatierra J, Castro J, Erickson A, Li Q, Braz J, Gilchrist J, Grundy L, Rychkov GY, Deiteren A, Rais R, King GF, Slusher BS, Basbaum A, Pasricha PJ, Brierley SM, Bosmans F. PMID: 29875317; PMCID: PMC6124407.
      View in: PubMed   Mentions: 19     Fields:    Translation:HumansAnimalsCells
    25. Synergistic antipruritic effects of gamma aminobutyric acid A and B agonists in a mouse model of atopic dermatitis. J Allergy Clin Immunol. 2017 Aug; 140(2):454-464.e2. Cevikbas F, Braz JM, Wang X, Solorzano C, Sulk M, Buhl T, Steinhoff M, Basbaum AI. PMID: 28232084; PMCID: PMC5546982.
      View in: PubMed   Mentions: 15     Fields:    Translation:AnimalsCells
    26. Rebuilding CNS inhibitory circuits to control chronic neuropathic pain and itch. Prog Brain Res. 2017; 231:87-105. Braz JM, Etlin A, Juarez-Salinas D, Llewellyn-Smith IJ, Basbaum AI. PMID: 28554402.
      View in: PubMed   Mentions: 7     Fields:    Translation:HumansAnimalsCells
    27. Peripheral and central neuronal ATF3 precedes CD4+ T-cell infiltration in EAE. Exp Neurol. 2016 09; 283(Pt A):224-34. Frezel N, Sohet F, Daneman R, Basbaum AI, Braz JM. PMID: 27343802; PMCID: PMC5500277.
      View in: PubMed   Mentions: 16     Fields:    Translation:AnimalsCells
    28. Injured sensory neuron-derived CSF1 induces microglial proliferation and DAP12-dependent pain. Nat Neurosci. 2016 Jan; 19(1):94-101. Guan Z, Kuhn JA, Wang X, Colquitt B, Solorzano C, Vaman S, Guan AK, Evans-Reinsch Z, Braz J, Devor M, Abboud-Werner SL, Lanier LL, Lomvardas S, Basbaum AI. PMID: 26642091; PMCID: PMC4703328.
      View in: PubMed   Mentions: 219     Fields:    Translation:AnimalsCells
    29. Dorsal Horn Parvalbumin Neurons Are Gate-Keepers of Touch-Evoked Pain after Nerve Injury. Cell Rep. 2015 Nov 10; 13(6):1246-1257. Petitjean H, Pawlowski SA, Fraine SL, Sharif B, Hamad D, Fatima T, Berg J, Brown CM, Jan LY, Ribeiro-da-Silva A, Braz JM, Basbaum AI, Sharif-Naeini R. PMID: 26527000; PMCID: PMC6038918.
      View in: PubMed   Mentions: 145     Fields:    Translation:AnimalsCells
    30. CT-guided injection of a TRPV1 agonist around dorsal root ganglia decreases pain transmission in swine. Sci Transl Med. 2015 Sep 16; 7(305):305ra145. Brown JD, Saeed M, Do L, Braz J, Basbaum AI, Iadarola MJ, Wilson DM, Dillon WP. PMID: 26378245; PMCID: PMC4854290.
      View in: PubMed   Mentions: 27     Fields:    Translation:AnimalsCells
    31. Transplant restoration of spinal cord inhibitory controls ameliorates neuropathic itch. J Clin Invest. 2014 Aug; 124(8):3612-6. Braz JM, Juarez-Salinas D, Ross SE, Basbaum AI. PMID: 25003193; PMCID: PMC4109547.
      View in: PubMed   Mentions: 23     Fields:    Translation:AnimalsCells
    32. Transmitting Pain and Itch Messages: A Contemporary View of the Spinal Cord Circuits that Generate Gate Control. Neuron. 2014 Jun 1; 82(6):1407. Braz BJ, Solorzano SC, Wang WX, Basbaum BA. .
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    33. Sciatic nerve transection triggers release and intercellular transfer of a genetically expressed macromolecular tracer in dorsal root ganglia. J Comp Neurol. 2011 Sep 01; 519(13):2648-57. Bráz JM, Ackerman L, Basbaum AI. PMID: 21484801; PMCID: PMC3864657.
      View in: PubMed   Mentions: 7     Fields:    Translation:HumansAnimalsCells
    34. Restriction of transient receptor potential vanilloid-1 to the peptidergic subset of primary afferent neurons follows its developmental downregulation in nonpeptidergic neurons. J Neurosci. 2011 Jul 13; 31(28):10119-27. Cavanaugh DJ, Chesler AT, Bráz JM, Shah NM, Julius D, Basbaum AI. PMID: 21752988; PMCID: PMC3147010.
      View in: PubMed   Mentions: 144     Fields:    Translation:AnimalsCells
    35. Differential ATF3 expression in dorsal root ganglion neurons reveals the profile of primary afferents engaged by diverse noxious chemical stimuli. Pain. 2010 Aug; 150(2):290-301. Bráz JM, Basbaum AI. PMID: 20605331; PMCID: PMC2922479.
      View in: PubMed   Mentions: 78     Fields:    Translation:AnimalsCells
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    37. Triggering genetically-expressed transneuronal tracers by peripheral axotomy reveals convergent and segregated sensory neuron-spinal cord connectivity. Neuroscience. 2009 Nov 10; 163(4):1220-32. Bráz JM, Basbaum AI. PMID: 19647044; PMCID: PMC2760676.
      View in: PubMed   Mentions: 26     Fields:    Translation:AnimalsCells
    38. Inputs to serotonergic neurons revealed by conditional viral transneuronal tracing. J Comp Neurol. 2009 May 10; 514(2):145-60. Braz JM, Enquist LW, Basbaum AI. PMID: 19274668; PMCID: PMC2696271.
      View in: PubMed   Mentions: 33     Fields:    Translation:AnimalsCells
    39. Chapter 22 The Endogenous Neuromodulation System. Neuromodulation. 2009 Jan 1; 303-312. Basbaum BA, Braz BJ, Ossipov OM, Porreca PF. .
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    40. Innocuous, not noxious, input activates PKCgamma interneurons of the spinal dorsal horn via myelinated afferent fibers. J Neurosci. 2008 Aug 06; 28(32):7936-44. Neumann S, Braz JM, Skinner K, Llewellyn-Smith IJ, Basbaum AI. PMID: 18685019; PMCID: PMC3844752.
      View in: PubMed   Mentions: 94     Fields:    Translation:AnimalsCells
    41. Genetically expressed transneuronal tracer reveals direct and indirect serotonergic descending control circuits. J Comp Neurol. 2008 Apr 20; 507(6):1990-2003. Braz JM, Basbaum AI. PMID: 18273889; PMCID: PMC4947410.
      View in: PubMed   Mentions: 27     Fields:    Translation:AnimalsCells
    42. Parallel "pain" pathways arise from subpopulations of primary afferent nociceptor. Neuron. 2005 Sep 15; 47(6):787-93. Braz JM, Nassar MA, Wood JN, Basbaum AI. PMID: 16157274.
      View in: PubMed   Mentions: 134     Fields:    Translation:AnimalsCells
    43. [From inflammation to pain: experimental gene therapy]. Med Sci (Paris). 2004 Mar; 20(3):325-30. Meunier A, Braz J, Cesselin F, Hamon M, Pohl M. PMID: 15067578.
      View in: PubMed   Mentions:    Fields:    Translation:HumansAnimals
    44. Gene therapy of chronic pain. Curr Gene Ther. 2003 Jun; 3(3):223-38. Pohl M, Meunier A, Hamon M, Braz J. PMID: 12762481.
      View in: PubMed   Mentions: 3     Fields:    Translation:HumansAnimals
    45. Gene therapy of pain: emerging strategies and future directions. Eur J Pharmacol. 2001 Oct 19; 429(1-3):39-48. Pohl M, Braz J. PMID: 11698025.
      View in: PubMed   Mentions: 8     Fields:    Translation:HumansAnimals
    46. Therapeutic efficacy in experimental polyarthritis of viral-driven enkephalin overproduction in sensory neurons. J Neurosci. 2001 Oct 15; 21(20):7881-8. Braz J, Beaufour C, Coutaux A, Epstein AL, Cesselin F, Hamon M, Pohl M. PMID: 11588161; PMCID: PMC6763863.
      View in: PubMed   Mentions: 46     Fields:    Translation:AnimalsCells
    47. Effets analgésiques des morphiniques et systèmes opioïdergiques dans les douleurs chroniques: confrontation des données cliniques et des données expérimentales chez l’animal. Douleur et Analgésie. 2001 Mar 1; 14(1):49-58. Braz BJ, Coutaux CA. .
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    48. Met-enkephalin is preferentially transported into the peripheral processes of primary afferent fibres in both control and HSV1-driven proenkephalin A overexpressing rats. Neuroscience. 2001; 103(4):1073-83. Antunes bras J, Becker C, Bourgoin S, Lombard M, Cesselin F, Hamon M, Pohl M. PMID: 11301214.
      View in: PubMed   Mentions: 14     Fields:    Translation:AnimalsCells
    49. Effects of peripheral axotomy on cholecystokinin neurotransmission in the rat spinal cord. J Neurochem. 1999 Feb; 72(2):858-67. Antunes Bras JM, Laporte AM, Benoliel JJ, Bourgoin S, Mauborgne A, Hamon M, Cesselin F, Pohl M. PMID: 9930763.
      View in: PubMed   Mentions: 4     Fields:    Translation:AnimalsCells
    50. Herpes simplex virus 1-mediated transfer of preproenkephalin A in rat dorsal root ganglia. J Neurochem. 1998 Mar; 70(3):1299-303. Antunes Bras JM, Epstein AL, Bourgoin S, Hamon M, Cesselin F, Pohl M. PMID: 9489753.
      View in: PubMed   Mentions: 24     Fields:    Translation:HumansAnimalsCells
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