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Michael J. Caterina, MD, PhD

Department Affiliations Neurosurgery, Biological Chemistry,
Rank Professor, Director, Neurosurgery Pain Research
Office Phone 410-502-5457
Lab Phone 410-614-1230
Fax 410-955-5759
Email caterina@jhmi.edu
SOM Address Room 408 Biophysics Building
Website
Students

Tiffany Link 2006 – 2010

Research Interests

Molecular and Cellular Mechanisms of Pain Sensation

My lab studies mechanisms underlying pain sensation. One focus of the lab is a group of ion channel proteins of the Transient Receptor Potential Vanilloid (TRPV) family. These channels share the intriguing feature that they can be activated by warm or painfully hot temperatures, as well as by many nonthermal stimuli. For example, TRPV1, the founding member of this family, can be activated by painful heat (>42°C), by protons, or by pungent chemicals such as capsaicin. This channel is strongly expressed in nociceptive neurons and is essential for normal behavioral responses to noxious heat. By examining these channels in recombinant and native systems, and taking advantage of knockout mice lacking one or more subtypes, we are dissecting the biological contributions of these channels to pain sensation and other processes in both neuronal and nonneuronal cells. A second focus of the lab is the use of cutting-edge molecular, cellular, genetic, behavioral and physiological approaches to understand the biological and pathophysiological basis of chronic pain in animal models and in human disease.

Current areas of emphasis include:

  • Understanding the mechanisms by which keratinocytes in the skin contribute to “indirect” pain perception by signaling to epidermal nerve endings under healthy conditions and in painful disease states in both animal models and human patients.
  • Uncovering non-nociceptive roles for TRPV channels in epithelial cells of the skin and urinary bladder.
  • Developing novel assays and reagents for the quantification and characterization of acute nociception and chronic pain
  • Dissecting the cellular and molecular events that contribute to neuropathic pain and exploring strategies to reverse this condition

Publications

Caterina Research Profile

  • Munns CH, Chung MK, Amzel LM, and Caterina MJ. (2015) Role of the outer pore domain in TRPV1 dynamic permeability to large cations. J. Biol Chem. 290: 5707-5724. PMID 25568328
  • Pang Z, Sakamoto T, Kim YS, Yang F, Guan Y, Dong X, Guler A, Caterina MJ. Keratinocyte stimulation is sufficient to evoke nociception in the mouse (2015) Pain Apr;156(4):656-65. (cover article) PMID 25790456
  • Hua ZL, Jeon S, Caterina MJ, and Nathans JN. Frizzled3 is required for the development of multiple axon tracts in the mouse central nervous system. Proc. Natl. Acad. Sci. U.S.A. Jul 22;111(29):E3005-14.PMID 24799694
  • Kim YS, Chu Y, Han L, Li M, Li Z, LaVinka PC, Sun S, Tang Z, Park K, Caterina MJ, Ren K, Dubner R, Wei F and Dong X. Central Terminal Sensitization of TRPV1 by Descending Serotonergic Facilitation Modulates Chronic Pain. Neuron (2014) Feb 19;81(4):873-87. PMID 24462040
  • Caterina MJ (2014) TRP channel cannabinoid targets and skin inflammation ACS Chem Neurosci. 5(11):1107-16 PMID 24915599
  • Park U, Vastani N, Guan Y, Raja S, Koltzenberg M. and Caterina MJ. TRPV2 knockout mice are susceptible to perinatal lethality but display normal thermal and mechanical nociception (2011) J Neurosci. 31(32):11425-36.
  • Huang SM, Li X, Yu Y, Wang J, Caterina MJ. TRPV3 and TRPV4 ion channels are not major contributors to mouse heat sensation. (2011) Mol Pain. 2011 May 17;7(1):37.PMID 21832173
  • Cheng X, Jin, J, Hu L, Shen D, Dong X, Samie MA, Knoff J, Eisinger B, Liu M, Huang SM, Caterina MJ, Dempsey P, Michael E, Dlugosz A, Andrews NC, Clapham DE, and Xu H. A Keratinocyte TRP Channel Controls Hair Morphogenesis and Skin Barrier Formation via EGFR signaling and Transglutaminase Activity. (2010) Cell 141, 331-343. PMID 20403327
  • Link TM, Park U, Vonakis BM, Raben DM, Soloski MJ, Caterina MJ. TRPV2 has a pivotal role in macrophage particle binding and phagocytosis. (2010) Nature Immunology 11, 232-239.PMID 20118928
  • Landouré G, Zdebik AA, Martinez TL, Burnett BG, Stanescu HC, Inada H, Shi Y, Taye AA, Kong L, Munns CH, Choo SS, Phelps CB, Paudel R, Houlden H, Ludlow CL, Caterina MJ, Gaudet R, Kleta R, Fischbeck KH, Sumner CJ. Mutations in TRPV4 cause Charcot-Marie-Tooth disease type 2C Nature Genet. (2010) Feb;42(2):170-4. PMID 20037586
  • Huang SM, Lee H, Chung MK, Park, U, Yu YY, Bradshaw H, Coulombe PA, Walker JM, and Caterina MJ. Skin keratinocyte TRPV3 ion channels modulate pain sensitivity via prostaglandin E2. (2008) J. Neurosci. 28, 13727- 13737. PMID 19091963
  • Chung MK, Guler AD and Caterina MJ. TRPV1 exhibits dynamic ionic selectivity during agonist stimulation. (2008) Nature Neuroscience 11, 555-564 (Highlighted in Nat Neurosci. 2008 May;11(5):528-9)PMID 18391945
  • Moussaieff A, Rimmerman N, Bregman T, Straiker A, Felder CC, Shoham S, Kashman Y, Huang SM, Lee H, Shohami E, Mackie K, Caterina MJ, Walker JM, Fride E and Mechoulam R. Incensole acetate, an incense component, elicits psychoactivity by activating TRPV3 channels in the brain (2008) FASEB J 22(8):3024-34.PMID 18492727
  • Lumpkin EA and Caterina MJ,Mechanisms of Sensory Transduction in the Skin. (2007) Nature 445(7130):858-65. PMID 17314972
  • Birder L, Negoita F, Lee H, de Groat W, Kanai A, Barrick S, Meyers S, and Caterina, MJ. Activation of Urothelial-TRPV4 by 4a-PDD contributes to altered bladder reflexes in the rat. (2007) J Pharmacol Exp Ther. 323(1):227-35. PMID 17636010
  • Sidhaye VK, Guler AD, Schweitzer KS, D’Alessio F, Caterina MJ and King LS Transient receptor potential vanilloid 4 regulates aquaporin-5 abundance under hypotonic conditions. (2006) Proc. Natl. Acad. Sci., USA 103(12):4747-52. PMID 16537379
  • Shimizu I, Iida T, Horiuchi N and Caterina MJ. 5-Iodoresiniferatoxin evokes hypothermia in mice and is a partial TRPV1 agonist in vitro .(2005) J. Pharm. Exp. Ther., 314:1378-85. PMID 15947039
  • Shimizu I, Iida T, Guan Y, Zhao C, Raja SN, Jarvis MF, Cockayne DA, and Caterina MJ. Enhanced thermal avoidance in mice lacking the ATP receptor P2X3. (2005) Pain, 116, 96-108.PMID 15927378
  • Pogatzki-Zahn E,, Shimizu I, Caterina MJ and Raja SN. Heat hyperalgesia after incision requires TRPV1 and is distinct from pure inflammatory pain. (2005) Pain, 115, 296-307. PMID 15911156
  • Chung MK, Guler AD, and Caterina MJ. Biphasic currents evoked by chemical or thermal activation of the heat-gated ion channel, TRPV3. (2005) J. Biol Chem. 280, 15928-15941. PMID 15722340
  • Lee H, Iida T, Mizuno A, Suzuki M, Caterina MJ. Altered thermal preference in mice lacking TRPV4. (2005) J. Neurosci. 25 1304-10. PMID 15689568
  • Iida T, Shimizu I, Nealen ML, Campbell, A., and Caterina MJ. Attenuated fever response in mice lacking TRPV1. (2005) Neurosci. Lett. 378, 28-33.
  • Chung MK, Lee H, Mizuno A, Suzuki M, Caterina MJ. 2-aminonethoxydiphenyl borate activates and sensitizes the heat-gated ion channel, TRPV3. (2004) J. Neurosci. 24, 5177-5182.
  • Chung MK, Lee H, Mizuno A, Suzuki M, Caterina MJ . TRPV3 and TRPV4 mediate warmth-evoked currents in primary mouse keratinocytes. (2004) J Biol. Chem. 279, 21569-21575.
  • Nealen M, Thut P, Gold M and Caterina MJ. TRPM8 is expressed in a subset of cold-responsive trigeminal neurons from rat. (2003) J. Neurophysiology 90, 515-520.
  • Birder LA, Nakamura Y, Kiss S, Nealen ML, Barrick S, Kanai AJ, Wang E, Ruiz G, De Groat WC, Apodaca G, Watkins S, Caterina M.J. Altered urinary bladder function in mice lacking the vanilloid receptor TRPV1. (2002) Nature Neurosci. 5, 856-860.
  • Guler A, Lee H, Iida T, Shimizu I, Tominaga M, and Caterina MJ. Heat-evoked activation of the ion channel, TRPV4. (2002) J. Neurosci. 22, 6408-6414.
  • Caterina MJ, Leffler A, Malmberg A, Martin W, Trafton J, Petersen-Zeitz KR, Koltzenberg M, Basbaum A and Julius D (2000) Impaired nociception and pain sensation in mice lacking the capsaicin receptor. Science 288, 306-313. (cover article)
  • Caterina MJ, Rosen A, Tominaga M, Brake AJ, and Julius D (1999) A capsaicin receptor homologue with a threshold for noxius heat. Nature, 398, 436-441.
  • Caterina MJ, Schumacher M, Tominaga M,, Rosen TA, Levine JD and Julius, D. The capsaicin receptor, a heat-activated ion channel in the pain pathway. (1997) Nature, 389, 816-824.