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David D. McKemy

PIBBS Guest Faculty

Associate Professor
Head, Section of Neurobiology
Department of Biological Sciences

David D. McKemy

Research Topics

  • The molecular basis for the sensations of touch and pain.
  • Cellular mechanisms mediating sensitization after injury, or during disease.
  • Genetic basis of sensory signaling.

Research Images

Identification of a cold and menthol receptor reveals a general role for TRP channels in thermosensation.
Identification of a cold and menthol receptor reveals a general role for TRP channels in thermosensation.
Labeling of neurons expressing TRPM8 (green) and TRPV1 (red) in mouse dorsal root ganglia.
Labeling of neurons expressing TRPM8 (green) and TRPV1 (red) in mouse dorsal root ganglia.
Using mice lacking functional copies of TRPM8, TRPA1 or both ion channels, this study shows that noxious cold signaling is exclusive to TRPM8, mediating neural and behavioral responses to cold and cold mimetics in mammals.
Using mice lacking functional copies of TRPM8, TRPA1 or both ion channels, this study shows that noxious cold signaling is exclusive to TRPM8, mediating neural and behavioral responses to cold and cold mimetics in mammals.
Trigeminal ganglia section demonstrating expression of a GFP transgene in cold-sensing, TRPM8 neurons.
Trigeminal ganglia section demonstrating expression of a GFP transgene in cold-sensing, TRPM8 neurons.

Research Overview

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.

Contact Information

Mailing Address University of Southern California
3641 Watt Way, HNB 228
Los Angeles CA 90089
Office Location HNB 201
Office Phone (213) 821-5724
Lab Location HNB 201
Lab Phone (213) 740-5473
Fax
Office Location HNB 201

Websites

Education

  • B.S. Biochemistry, University of Nevada, Reno 1991
  • Ph.D., Cellular & Molecular Pharmacology & Physiology, University of Nevada, Reno 1999.
  • Post-Doctoral Fellow, University of California, San Francisco, 1999-2003

Selected Publications

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  • Palkar R, Lippoldt EK, McKemy DD. (2015) The molecular and cellular basis of thermosensation in mammals. Curr Opin Neurobiol. 2015 Jan 23;34C:14-19 PubMed
  • Kim, Y.S., Park, J.H., Choi, S.J., Bae, J.Y., Ahn, D.K., McKemy, D.D., Bae, Y.C. (2014) Central connectivity of transient receptor potential melastatin 8-expressing axons in the brain stem and spinal dorsal horn. PLoS One. 2014 Apr 7;9(4):e94080. PubMed
  • Lippoldt EK, Elmes RR, McCoy DD, Knowlton WM, McKemy DD. (2013) Artemin, a glial cell line-derived neurotrophic factor family member , induces TRPM8-dependent cold pain. J Neurosci. 24;33(30):12543-52. PubMed
  • 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. 110(18):7476-81 PubMed
  • 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. 33(7):2837-48. PubMed
  • McKemy, D.D. (2013). The Molecular and Cellular Basis of Cold Sensation. ACS Chem. Neurosci., 4(2):238-47.
    PubMed
  • Knowlton WM, Daniels RL, Palkar R, McCoy DD, McKemy DD. (2011) Pharmacological blockade of TRPM8 ion channels alters cold and cold pain responses in mice. PLoS ONE 6(9): e25894. PubMed
  • Knowlton WM, Bifolck-Fisher A, Bautista DM, McKemy DD. (2010) TRPM8, but not TRPA1, is required for neural and behavioral responses to noxious cold temperatures and cold-mimetics in vivo. Pain, 150: 340-350. Epub 2010 Jun 12 (Work highlighted on the August cover) PubMed
  • Takashima, Y., Daniels, R.L., Knowlton, W., Teng, J., Liman, E.R., and McKemy, D.D. (2007) Diversity in the neural circuitry of cold sensing revealed by genetic axonal labeling of TRPM8 neurons. Journal of Neuroscience. Dec 19; 27(51):14147-14157.

    Highlighted in Nature Reviews Neuroscience 9, 79 (February 2008).

    PubMed
  • McKemy DD, Neuhausser WM, Julius D (2002) Identification of a cold receptor reveals a general role for TRP channels in thermosensation. Nature. 416:52-58. PubMed