David McKemy

• Post-doctoral fellow, University of California, San Francisco, 11/01/1999 – 12/31/2003

Tenure Track Appointments

• Associate Professor, University of Southern California, 04/19/2011 –
• Assistant Professor, University of Southern California, 01/04/2004 – 04/18/2011

Summary Statement of Research Interests

My laboratory is generally interested in the neurobiological logic behind our ability to detect touch and pain. These fundamental processes, termed somatosensation and nociception, respectively, allow for the detection of chemical, mechanical, and thermal stimuli, and can critically differentiate between innocuous and noxious stimuli. Peripheral sensory neurons are the principle sensors of these stimuli and convert these environmental cues into ascending neural activity. Research in my lab aims to understand the molecular and cellular basis of this fundamental sensory process.

We and others have begun to identify the molecules that are the primary detectors of thermal and painful stimuli in the peripheral nervous system. Using natural products such as capsaicin, menthol, and mustard oil, the active components of hot chili peppers, mint, and wasabi, respectively, ion channels that mediate the psychophysical sensations of hot (TRPV1, TRPV2), cold (TRPM8), and pungency (TRPA1) were cloned. Indeed, a conserved cellular mechanism has emerged in which members of the TRP (transient receptor potential) family of ion channels are detectors of thermal and pungent stimuli in sensory afferents.

To pursue our research interests, we use a combination of molecular, cellular, genetic, electrophysiological, and biochemical approaches in the laboratory to understand how these channels detect and transduce these discrete environmental stimuli. Specifically, we wish to understand how these channels are activated, what is their involvement in peripheral sensitization after injury or during disease, what are their roles in behavioral responses to environmental stimuli, and identify the neural networks involved in transmitting peripheral stimuli centrally.

It is our hope that these studies will provide insights into the mechanisms that lead to the formation of aberrant activity of sensory neurons involved in the detection and transduction of these stimuli, thereby leading to the development of novel therapeutic targets that can be used to alleviate debilitating conditions associated with inflammatory and neuropathic pain.

Journal Article

• McCoy, D. D., Zhuo, L., Nguyen, A., Watts, A. G., Donovan, C. M., McKemy, D. D. (2013). Enhanced insulin clearance in mice lacking TRPM8 channels. AJP-Endo Metab. Vol. In press
• Ramachandran, R., Hyun, E., Zhao, L., Lapointe, T. L., Chapman, K., Hirota, C. L., Ghosh, S., McKemy, D. D., Vergnolle, N., Beck, P. L., Altier, C., Hollenberg, M. D. (2013). TRPM8 activation attenuates inflammatory responses in mouse models of colitis. Proc Natl Acad Sci. Vol. 110 (18), pp. 7476-81. PubMed Web Address
• Knowlton, W. M., Palkar, R., Lippoldt, E. K., McCoy, D. D., Baluch, F., Chen, J., McKemy, D. D. (2013). A Sensory-Labeled Line for Cold: TRPM8-Expressing Sensory Neurons Define the Cellular Basis for Cold, Cold Pain, and Cooling-Mediated Analgesia. Journal of Neuroscience. Vol. 33 (7), pp. 2837-48. PubMed Web Address
• McKemy, D. D. (2013). The Molecular and Cellular Basis of Cold Sensation. ACS Chem Neuroscience. Vol. 4 (2), pp. 38-47. PubMed Web Address
• Osborne, M., Gomez, D., Feng, Z., McEwen, C., Beltran, J., Cirillo, K., El-Khodor, B., Lin, M. Y., Li, Y., Knowlton, W. M., McKemy, D. D., Bogdanik, L., Butts-Dehm, K., Martens, K., Davis, C., Doty, R., Wardwell, K., Ghavami, A., Kobayashi, D., Ko, C. P., Ramboz, S., Lutz, C. (2012). Characterization of behavioral and neuromuscular junction phenotypes in a novel allelic series of SMA mouse models. Hum Mol Genet. Vol. 21 (20), pp. 4431-47. PubMed Web Address
• Knowlton, W. M., Daniels, R. L., Palkar, R., McCoy, D. D., McKemy, D. D. (2011). Pharmacological blockade of trpm8 ion channels alters cold and cold pain responses in mice. PloS One. Vol. 6 (9), pp. e25894. PubMed Web Address
• McCoy, D. D., Knowlton, W. R., McKemy, D. D. (2011). Scraping through the ice: Uncovering the role of TRPM8 in cold transduction. Am J Physiol Regul Integr Comp Physiol.. Vol. 300 (6), pp. R1278-1287. PubMed Web Address
• McKemy, D. D. (2011). A Spicy Family Tree: TRPV1 and its Nociceptive Lineage. The Embo Journal. Vol. 30 (3), pp. 453-455. PubMed Web Address
• Knowlton, W. M., McKemy, D. D. (2011). TRPM8: From Cold to Cancer, Peppermint to Pain. Curr Pharm Biotechnol. Vol. 12 PubMed Web Address
• McKemy, D. D., Daniels, R. L. (2010). Design and Construction of a Two-Temperature Preference Behavioral Assay for Undergraduate Neuroscience Laboratories. The Journal of Undergraduate Neuroscience Education (JUNE). Vol. 9 (1), pp. A51-A56.
• Knowlton, W. M., Bifolck-Fisher, A., Bautista, D. M., McKemy, D. D. (2010). TRPM8, but not TRPA1, is required for neural and behavioral responses to acute noxious cold temperatures and cold-mimetics in vivo. Pain. Vol. 150 (2), pp. 340-50. PubMed Web Address
• Takashima, Y., Ma, L., McKemy, D. D. (2010). The development of peripheral cold neural circuits based on TRPM8 expression. Neuroscience. Vol. 169 (2), pp. 828-42.
• McKemy, D. D. (2010). Therpeutic potential of TRPM8 modulators. The Open Access Drug Discovery Journal. Vol. 2, pp. 80-87.
• Mandadi, S., Nakanishi, S. T., Takashima, Y., Dhaka, A., Patapoutian, A., McKemy, D. D., Whelan, P. J. (2009). Locomotor networks are targets of modulation by sensory transient receptor potential vanilloid 1 and transient receptor potential melastatin 8 channels. Neuroscience. Vol. 162 (4), pp. 1377-97.
• Stucky, C. L., Dubin, A. E., Jeske, N. A., Malin, S. A., McKemy, D. D., Story, G. M. (2009). Roles of transient receptor potential channels in pain. Brain Res Rev. Vol. 60 (1), pp. 2-23.
• Carr, R. W., Pianova, S., McKemy, D. D., Brock, J. A. (2009). Action potential initiation in the peripheral terminals of cold-sensitive neurones innervating the guinea-pig cornea. J Physiol. Vol. 587 (Pt 6), pp. 1249-64.
• Daniels, R. L., Takashima, Y., McKemy, D. D. (2009). Activity of the neuronal cold sensor TRPM8 is regulated by phospholipase C via the phospholipid phosphoinositol 4,5-bisphosphate. J Biol Chem. Vol. 284 (3), pp. 1570-82.
• Wang, Y. Y., Chang, R. B., Waters, H. N., McKemy, D. D., Liman, E. R. (2008). The nociceptor ion channel TRPA1 is potentiated and inactivated by permeating calcium ions. J Biol Chem. Vol. 283 (47), pp. 32691-703.
• Takashima, Y., Daniels, R. L., Knowlton, W., Teng, J., Liman, E. R., McKemy, D. D. (2007). Diversity in the neural circuitry of cold sensing revealed by genetic axonal labeling of transient receptor potential melastatin 8 neurons. J Neurosci. Vol. 27 (51), pp. 14147-57.
• Daniels, R. L., McKemy, D. D. (2007). Mice left out in the cold: commentary on the phenotype of TRPM8-nulls. Mol Pain. Vol. 3, pp. 23.
• McKemy, D. D. (2007). Temperature sensing across species. Pflugers Arch. Vol. 454 (5), pp. 777-91.
• McNamara, N., Gallup, M., Sucher, A., Maltseva, I., McKemy, D. D., Basbaum, C. (2006). AsialoGM1 and TLR5 cooperate in flagellin-induced nucleotide signaling to activate Erk1/2. Am J Respir Cell Mol Biol. Vol. 34 (6), pp. 653-60.
• McKemy, D. D. (2005). How cold is it? TRPM8 and TRPA1 in the molecular logic of cold sensation. Mol Pain. Vol. 1, pp. 16.
• Jordt, S. E., Bautista, D. M., Chuang, H. H., McKemy, D. D., Zygmunt, P. M., Hogestatt, E. D., Meng, I. D., Julius, D. (2004). Mustard oils and cannabinoids excite sensory nerve fibres through the TRP channel ANKTM1. Nature. Vol. 427 (6971), pp. 260-5.
• Jordt, S. E., McKemy, D. D., Julius, D. (2003). Lessons from peppers and peppermint: the molecular logic of thermosensation. Curr Opin Neurobiol. Vol. 13 (4), pp. 487-92.
• Kataoka, H., Hamilton, J. R., McKemy, D. D., Camerer, E., Zheng, Y. W., Cheng, A., Griffin, C., Coughlin, S. R. (2003). Protease-activated receptors 1 and 4 mediate thrombin signaling in endothelial cells. Blood. Vol. 102 (9), pp. 3224-31.
• McKemy, D. D., Neuhausser, W. M., Julius, D. (2002). Identification of a cold receptor reveals a general role for TRP channels in thermosensation. Nature. Vol. 416 (6876), pp. 52-8.
• McNamara, N., Khong, A., McKemy, D. D., Caterina, M., Boyer, J., Julius, D., Basbaum, C. (2001). ATP transduces signals from ASGM1, a glycolipid that functions as a bacterial receptor. Proc Natl Acad Sci U S A. Vol. 98 (16), pp. 9086-91.
• McKemy, D. D., Welch, W., Airey, J. A., Sutko, J. L. (2000). Concentrations of caffeine greater than 20 mM increase the indo-1 fluorescence ratio in a Ca(2+)-independent manner. Cell Calcium. Vol. 27 (2), pp. 117-24.
• Oppenheim, R. W., Prevette, D., Houenou, L. J., Pincon-Raymond, M., Dimitriadou, V., Donevan, A., O’Donovan, M., Wenner, P., McKemy, D. D., Allen, P. D. (1997). Neuromuscular development in the avian paralytic mutant crooked neck dwarf (cn/cn): further evidence for the role of neuromuscular activity in motoneuron survival. J Comp Neurol. Vol. 381 (3), pp. 353-72.
• Ivanenko, A., McKemy, D. D., Kenyon, J. L., Airey, J. A., Sutko, J. L. (1995). Embryonic chicken skeletal muscle cells fail to develop normal excitation-contraction coupling in the absence of the alpha ryanodine receptor. Implications for a two-ryanodine receptor system. J Biol Chem. Vol. 270 (9), pp. 4220-3.
• Kenyon, J. L., McKemy, D. D., Airey, J. A., Sutko, J. L. (1995). Interaction between ryanodine receptor function and sarcolemmal Ca2+ currents. Am J Physiol. Vol. 269 (2 Pt 1), pp. C334-40.
• Airey, J. A., Baring, M. D., Beck, C. F., Chelliah, Y., Deerinck, T. J., Ellisman, M. H., Houenou, L. J., McKemy, D. D., Sutko, J. L., Talvenheimo, J. (1993). Failure to make normal alpha ryanodine receptor is an early event associated with the crooked neck dwarf (cn) mutation in chicken. Dev Dyn. Vol. 197 (3), pp. 169-88.
• Airey, J. A., Deerinck, T. J., Ellisman, M. H., Houenou, L. J., Ivanenko, A., Kenyon, J. L., McKemy, D. D., Sutko, J. L. (1993). Crooked neck dwarf (cn) mutant chicken skeletal muscle cells in low density primary cultures fail to express normal alpha ryanodine receptor and exhibit a partial mutant phenotype. Dev Dyn. Vol. 197 (3), pp. 189-202.

• USC Raubenheimer Outstanding Junior Faculty Award, Shows unusual promise in the areas of research, teaching, and service to the University., 2010
• USC Neuroscience Graduate Program Faculty of the Year, 2006-2007
• Arthritis Foundation Post-Doctoral Fellowship, 2000 – 2003
• UCSF-Cardiovascular Research Institute Post-Doctoral Fellowship, 1999 – 2000
• American Heart Association Pre-Doctoral Fellowship, 1997 – 1999
• Glen E. Whiddett Biomedical Graduate Student Scholarship, 1998

Professional Memberships

• Society for Neuroscience, 2005 –
• Biophysical Society, 1994 – 2005