Joao Braz, PhD
ASSOC RES-FY
Anatomy
School of Medicine

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.

• Paradoxical increases in anterior cingulate cortex activity during nitrous oxide-induced analgesia reveal a signature of pain affect.
  bioRxiv : the preprint server for biology 2023 Weinrich JA, Liu CD, Jewell ME, Andolina CR, Bernstein MX, Benitez J, Rodriguez-Rosado S, Braz JM, Maze M, Nemenov MI, Basbaum AI
• Structure-based discovery of nonopioid analgesics acting through the α2A-adrenergic receptor.
  Science (New York, N.Y.) 2022 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, …
• TRPV1 drugs alter core body temperature via central projections of primary afferent sensory neurons.
  eLife 2022 Yue WWS, Yuan L, Braz JM, Basbaum AI, Julius D
• Intraspinal Transplantation of Precursors of Cortical GABAergic Interneurons to Treat Neuropathic Pain.
  2022 João M. Braz, Allan I. Basbaum
• ACVR1-activating mutation causes neuropathic pain and sensory neuron hyperexcitability in humans.
  Pain 2022 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
• Structure-Based Design of a Chemical Probe Set for the 5-HT5A Serotonin Receptor.
  Journal of medicinal chemistry 2022 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
• Structures of the σ2 receptor enable docking for bioactive ligand discovery.
  Nature 2021 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
• Regulatory T-cells inhibit microglia-induced pain hypersensitivity in female mice.
  eLife 2021 Kuhn JA, Vainchtein ID, Braz J, Hamel K, Bernstein M, Craik V, Dahlgren MW, Ortiz-Carpena J, Molofsky AB, Molofsky AV, Basbaum AI
• LB722 IL-31/IL31RA negatively regulate IL-4 production and cutaneous M2-like macrophage accumulation.
  Journal of Investigative Dermatology 2021 M.S. Fassett, J.M. Braz, C.A. Castellanos, A.W. Schroeder, M. Sadeghi, D.J. Mar, C.J. Zhou, J. Shin, A.I. Basbaum, K. Ansel
• Pain and itch processing by subpopulations of molecularly diverse spinal and trigeminal projection neurons.
  Proceedings of the National Academy of Sciences of the United States of America 2021 Wercberger R, Braz JM, Weinrich JA, Basbaum AI
• Contribution of dorsal horn CGRP-expressing interneurons to mechanical sensitivity.
  eLife 2021 Löken LS, Braz JM, Etlin A, Sadeghi M, Bernstein M, Jewell M, Steyert M, Kuhn J, Hamel K, Llewellyn-Smith IJ, Basbaum A
• Genetic priming of sensory neurons in mice that overexpress PAR2 enhances allergen responsiveness.
  Proceedings of the National Academy of Sciences of the United States of America 2021 Braz JM, Dembo T, Charruyer A, Ghadially R, Fassett MS, Basbaum AI
• Dorsal root ganglion macrophages contribute to both the initiation and persistence of neuropathic pain.
  Nature communications 2020 Yu X, Liu H, Hamel KA, Morvan MG, Yu S, Leff J, Guan Z, Braz JM, Basbaum AI
• Ablation of spinal cord estrogen receptor α-expressing interneurons reduces chemically induced modalities of pain and itch.
  The Journal of comparative neurology 2020 Tran M, Braz JM, Hamel K, Kuhn J, Todd AJ, Basbaum AI
• GABAergic cell transplants in the anterior cingulate cortex reduce neuropathic pain aversiveness.
  Brain : a journal of neurology 2019 Juarez-Salinas DL, Braz JM, Etlin A, Gee S, Sohal V, Basbaum AI
• Microcircuit Mechanisms through which Mediodorsal Thalamic Input to Anterior Cingulate Cortex Exacerbates Pain-Related Aversion.
  Neuron 2019 Meda KS, Patel T, Braz JM, Malik R, Turner ML, Seifikar H, Basbaum AI, Sohal VS
• Morphological and functional properties distinguish the substance P and gastrin-releasing peptide subsets of excitatory interneuron in the spinal cord dorsal horn.
  Pain 2019 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
• Pain relief by supraspinal gabapentin requires descending noradrenergic inhibitory controls.
  Pain reports 2018 Juarez-Salinas DL, Braz JM, Hamel KA, Basbaum AI
• NaV1.1 inhibition can reduce visceral hypersensitivity.
  JCI insight 2018 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
• Synergistic antipruritic effects of gamma aminobutyric acid A and B agonists in a mouse model of atopic dermatitis.
  The Journal of allergy and clinical immunology 2017 Cevikbas F, Braz JM, Wang X, Solorzano C, Sulk M, Buhl T, Steinhoff M, Basbaum AI
• Rebuilding CNS inhibitory circuits to control chronic neuropathic pain and itch.
  Progress in brain research 2017 Braz JM, Etlin A, Juarez-Salinas D, Llewellyn-Smith IJ, Basbaum AI
• Peripheral and central neuronal ATF3 precedes CD4+ T-cell infiltration in EAE.
  Experimental neurology 2016 Frezel N, Sohet F, Daneman R, Basbaum AI, Braz JM
• Injured sensory neuron-derived CSF1 induces microglial proliferation and DAP12-dependent pain.
  Nature neuroscience 2015 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
• Dorsal Horn Parvalbumin Neurons Are Gate-Keepers of Touch-Evoked Pain after Nerve Injury.
  Cell reports 2015 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
• CT-guided injection of a TRPV1 agonist around dorsal root ganglia decreases pain transmission in swine.
  Science translational medicine 2015 Brown JD, Saeed M, Do L, Braz J, Basbaum AI, Iadarola MJ, Wilson DM, Dillon WP
• Transplant restoration of spinal cord inhibitory controls ameliorates neuropathic itch.
  The Journal of clinical investigation 2014 Braz JM, Juarez-Salinas D, Ross SE, Basbaum AI
• Transmitting Pain and Itch Messages: A Contemporary View of the Spinal Cord Circuits that Generate Gate Control.
  Neuron 2014 João Braz, Carlos Solorzano, Xidao Wang, Allan I. Basbaum
• Sciatic nerve transection triggers release and intercellular transfer of a genetically expressed macromolecular tracer in dorsal root ganglia.
  The Journal of comparative neurology 2011 Bráz JM, Ackerman L, Basbaum AI
• Restriction of transient receptor potential vanilloid-1 to the peptidergic subset of primary afferent neurons follows its developmental downregulation in nonpeptidergic neurons.
  The Journal of neuroscience : the official journal of the Society for Neuroscience 2011 Cavanaugh DJ, Chesler AT, Bráz JM, Shah NM, Julius D, Basbaum AI
• Differential ATF3 expression in dorsal root ganglion neurons reveals the profile of primary afferents engaged by diverse noxious chemical stimuli.
  Pain 2010 Bráz JM, Basbaum AI
• 320 DIFFERENTIAL ATF3 EXPRESSION REVEALS THE PROFILE OF DORSAL ROOT GANGLION (DRG) NEURONS ACTIVATED BY DIVERSE NOXIOUS CHEMICAL STIMULI.
  European Journal of Pain 2009 J. Braz, A. Basbaum
• Triggering genetically-expressed transneuronal tracers by peripheral axotomy reveals convergent and segregated sensory neuron-spinal cord connectivity.
  Neuroscience 2009 Bráz JM, Basbaum AI
• Inputs to serotonergic neurons revealed by conditional viral transneuronal tracing.
  The Journal of comparative neurology 2009 Braz JM, Enquist LW, Basbaum AI
• Chapter 22 The Endogenous Neuromodulation System.
  Neuromodulation 2009 Allan I. Basbaum, Joao Braz, Michael H. Ossipov, Frank Porreca
• Innocuous, not noxious, input activates PKCgamma interneurons of the spinal dorsal horn via myelinated afferent fibers.
  The Journal of neuroscience : the official journal of the Society for Neuroscience 2008 Neumann S, Braz JM, Skinner K, Llewellyn-Smith IJ, Basbaum AI
• Genetically expressed transneuronal tracer reveals direct and indirect serotonergic descending control circuits.
  The Journal of comparative neurology 2008 Braz JM, Basbaum AI
• Parallel "pain" pathways arise from subpopulations of primary afferent nociceptor.
  Neuron 2005 Braz JM, Nassar MA, Wood JN, Basbaum AI
• [From inflammation to pain: experimental gene therapy].
  Medecine sciences : M/S 2004 Meunier A, Braz J, Cesselin F, Hamon M, Pohl M
• Gene therapy of chronic pain.
  Current gene therapy 2003 Pohl M, Meunier A, Hamon M, Braz J
• Gene therapy of pain: emerging strategies and future directions.
  European journal of pharmacology 2001 Pohl M, Braz J
• Therapeutic efficacy in experimental polyarthritis of viral-driven enkephalin overproduction in sensory neurons.
  The Journal of neuroscience : the official journal of the Society for Neuroscience 2001 Braz J, Beaufour C, Coutaux A, Epstein AL, Cesselin F, Hamon M, Pohl M
• 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 J. Braz, A. Coutaux
• 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 Antunes bras J, Becker C, Bourgoin S, Lombard M, Cesselin F, Hamon M, Pohl M
• Effects of peripheral axotomy on cholecystokinin neurotransmission in the rat spinal cord.
  Journal of neurochemistry 1999 Antunes Bras JM, Laporte AM, Benoliel JJ, Bourgoin S, Mauborgne A, Hamon M, Cesselin F, Pohl M
• Herpes simplex virus 1-mediated transfer of preproenkephalin A in rat dorsal root ganglia.
  Journal of neurochemistry 1998 Antunes Bras JM, Epstein AL, Bourgoin S, Hamon M, Cesselin F, Pohl M