My lab is interested in understanding how neuronal and nonneuronal cells in the body detect changes in ambient temperature. Increases or decreases in tissue temperature can cause pain, pleasure, or homeostatic changes in mammals, depending upon their direction, magnitude, and anatomical location. The molecular basis of this thermosensation, however, is poorly understood. We previously identified two heat-gated ion channels that are expressed in distinct subsets of peripheral neurons within the pain pathway. One of these proteins, TRPV1 (VR1), is a channel that can be activated not only by noxious heat (>43 C), but also by protons and by capsaicin (the main pungent ingredient in 'hot' peppers). The second channel, TRPV2, is activated by temperatures exceeding 52 C, but is insensitive to protons or capsaicin. Since then, we and others have identified several additional members of the TRP ion channel family that can be activated by either increases (TRPV3, TRPV4) or decreases (TRPM8) in temperature. Through a multidisciplinary approach involving molecular biology, biochemistry, calcium imaging, electrophysiology and mouse behavior, we are focusing on the following goals:

1. Using mouse knockouts of temperature-gated ion channels to clarify their roles in pain and temperature sensation.
   

2. Understanding how nonneuronal cells that express temperature-gated channels contribute to the process of thermosensation.
   

3. Determining how and why the ionic selectivity of TRPV channels is altered during their activation.
   

4. Uncovering non-thermosensory functions for temperature-gated TRPV ion channels

Publications:

Caterina, M.J., , Schumacher, M., Tominaga, M.,, Rosen, T.A., Levine, J.D. and Julius, D. (1997) The capsaicin receptor, a heat-activated ion channel in the pain pathway Nature, 389, 816-824.PubMed Reference

Caterina, M.J., Rosen, T.A., Tominaga, M., Brake, A.J., and Julius, D. (1999) A capsaicin receptor homologue with a threshold for noxius heat. Nature, 398, 436-441. PubMed Reference

Caterina, M.J., Leffler, A., Malmberg, A., Martin,W., Trafton, J., Petersen-Zeitz, K.R., 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)PubMed Reference

Birder, L.A., Kanai, A.J., de Groat, W.C., Kiss, S., Nealen, M.L., Burke, N.E., Dineley, K.E., Watkins, S., Reynolds, I.J. and Caterina, M.J. Vanilloid Receptor Expression Suggests a Sensory Role for Urinary Bladder Epithelial Cells (2001) Proc. Natl. Acad. Sci., U.S.A., 98, 13396 E3401.PubMed Reference

Guler, A., Lee, H., Iida, T., Shimizu, I. Tominaga, M., and Caterina, M.J. Heat-evoked activation of the ion channel, TRPV4 (2002) J. Neurosci. 22, 6408-6414.PubMed Reference

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.PubMed Reference

Birder, L.A., Nealen, M.L., Kiss, S., de Groat, W.C., Caterina, M.J., Wang, E., Apodaca, G. and Kanai, A.J. (2002) {beta}-Adrenoceptor Agonists Stimulate Endothelial Nitric Oxide Synthase in Rat Urinary Bladder Urothelial Cells J. Neurosci. 22, 8063-8070. PubMed Reference

Nealen, M., Thut, P., Gold, M. and Caterina, M.J. TRPM8 is expressed in a subset of cold-responsive trigeminal neurons from rat. (2003) J. Neurophysiology 90, 515-520.PubMed Reference

Chung, M.K., Lee, H. and Caterina, M.J. Warm Temperatures Activate TRPV4 in Mouse 308 Keratinocytes (2003) J. Biol. Chem. 278, 32037-32046PubMed Reference

Chung M.K., Lee H., Mizuno A., Suzuki M., Caterina M.J. TRPV3 and TRPV4 mediate warmth-evoked currents in primary mouse keratinocytes. (2004) J Biol. Chem. 279, 21569-21575.PubMed Reference

Chung M.K., Lee H., Mizuno A., Suzuki M., Caterina M.J. 2-aminonethoxydiphenyl borate activates and sensitizes the heat-gated ion channel, TRPV3 (2004) J. Neurosci. 24, 5177-5182.PubMed Reference

Zhang N., Rogers T.J., Caterina, MJ.. and Oppenheim J.J. Pro-inflammatory Chemokines, such as CCL3, Desensitizes m-opioid Receptors on Dorsal Root Ganglia Neurons (2004) J. Immunology 173, 594-599.PubMed Reference

Woodbury CJ, Zwick M, Wang S, Lawson JJ, Caterina MJ, Koltzenburg M, Albers KM, Koerber HR, and Davis BM. Nociceptors lacking TRPV1 and TRPV2 have normal heat responses (2004) J Neurosci. 24, 6410-5 PubMed Reference

Iida, T., Shimizu, I., Nealen, M.L., Campbell, A., and Caterina M.J. Attenuated fever response in mice lacking TRPV1 (2005) Neurosci. Lett. 378, 28-33. PubMed Reference

Lee, H., Iida, T., Mizuno, A., Suzuki, M., Caterina M.J. Altered thermal preference in mice lacking TRPV4 (2005) J. Neurosci. 25 1304-10. PubMed Reference

Zhang N., Inan S., Cowan A., Sun R., Wang J., Rogers T.J., Caterina M. J., and Oppenheim, J.J. A Pro-inflammatory chemokine, CCL3, sensitizes the heat- and capsaicin-gated ion channel, TRPV1 (2005) Proc. Natl. Acad. Sci., USA 102,4536-41.PubMed Reference

Chung, M.K., Guler A.D., and Caterina M.J. (2005), Biphasic currents evoked by chemical or thermal activation of the heat-gated ion channel, TRPV3. J. Biol Chem. 280, 15928-15941.PubMed Reference

Pogatzki-Zahn E.,, Shimizu I., Caterina, M., and Raja S.N. (2005) Heat hyperalgesia after incision requires TRPV1 and is distinct from pure inflammatory pain. Pain, 115, 296-307.PubMed Reference

Shimizu I., Iida T., Guan Y., Zhao C., Raja SN, Jarvis M.F., Cockayne D.A., and Caterina M.J. (2005) Enhanced thermal avoidance in mice lacking the ATP receptor P2X3 Pain, 116, 96-108.PubMed Reference

Shimizu I., Iida T., Horiuchi N. and Caterina M.J. (2005) 5-Iodoresiniferatoxin evokes hypothermia in mice and is a partial TRPV1 agonist in vitro J. Pharm. Exp. Ther., 314:1378-85.PubMed Reference

Sidhaye V.K., Guler A.D., Schweitzer K.S., D’Alessio F., Caterina M.J. and King L.S. (2006) Transient receptor potential vanilloid 4 regulates aquaporin-5 abundance under hypotonic conditions. Proc. Natl. Acad. Sci., USA 103(12):4747-52.PubMed Reference

Birder L., Negoita F., Lee H., de Groat W., Kanai A., Barrick S., Meyers S., and Caterina, M.J. (2007) Activation of Urothelial-TRPV4 by 4a-PDD contributes to altered bladder reflexes in the rat J Pharmacol Exp Ther. 323(1):227-35. PubMed Reference

Tan PL, Barr T, Inglis PN, Mitsuma N, Huang SM, Garcia-Gonzalez MA, Bradley BA, Coforio S, Albrecht PJ, Watnick T, Germino GG, Beales PL, Caterina MJ, Leroux MR, Rice FL, Katsanis N. (2007) Loss of Bardet Biedl syndrome proteins causes defects in peripheral sensory innervation and function. Proc Natl Acad Sci U S A. 104:17524-9. PubMed Reference

Lumpkin, E.A. and Caterina M.J. (2007) Mechanisms of Sensory Transduction in the Skin. Nature 445(7130):858-65.PubMed Reference

Moussaieff A., Rimmerman N., Bregman T., Straiker A., Felder C.C., Shoham S., Kashman Y., Huang S.M., Lee H., Shohami E., Mackie K., Caterina M.J., Walker J.M., Fride E. and Mechoulam R. (2008) Incensole acetate, an incense component, elicits psychoactivity by activating TRPV3 channels in the brain FASEB J 22(8):3024-34.PubMed Reference

Chung M.K., Guler A.D. and Caterina M.J. (2008) TRPV1 exhibits dynamic ionic selectivity during agonist stimulation Nature Neuroscience 11, 555-564 (Highlighted in Nat Neurosci. 2008 May;11(5):528-9)PubMed Reference

Sidhaye V.K., Schweitzer K.S., Caterina M.J., Shimoda L., King L.S. (2008) Shear-induced regulates AQP5 and airway epithelial barrier function. Proc. Natl. Acad. Sci. (USA) Mar 4;105(9):3345-50. PubMed Reference

Huang S.M., Lee H., Chung M.K., Park, U., Yu Y.Y., Bradshaw H., Coulombe P.A., Walker J.M., and Caterina M.J. (2008) Skin keratinocyte TRPV3 ion channels modulate pain sensitivity via prostaglandin E2. J. Neurosci. 28, 13727-13737.PubMed Reference

Park U., Vastani N., Guan Y., Raja S.N., Koltzenburg M., and Caterina M.J. TRPV2 does not mediate thermal or mechanical nociception but might play a role in low-threshold mechanotransduction in mice (Submitted)