University of Southern California

USC Neuroscience

David D. McKemy

Assistant Professor
Department of Biological Sciences
Neurobiology Section

Research Topics

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

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

Web Sites:
USC Neurobiology Section
NPR Story
Press release 12-19-07
E-mail:
mckemy@usc.edu
Mailing Address:
University of Southern California
3641 Watt Way, HNB 228
Los Angeles CA 90089
Office Location:
HNB 228A
Office Phone:
(213) 821-5724
Lab Location:
HNB 228
Lab Phone:
(213) 740-5473

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

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Selected Publications

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Mandadi S, Nakanishi S, Takashima Y, Dhaka A, Patapoutian A, McKemy D, Whelan P. (2009) Locomotor networks are targets of modulation by sensory TRPV1 and TRPM8 channels. Neuroscience May 28 [Epub ahead of print].

-PubMed

Carr, RW, Pianova, S, McKemy,DD, and Brock, JA. (2009) Action potential initiation in the peripheral terminals of cold-sensitive neurones innervating the guinea-pig cornea. J Physiol. Mar 15;587(Pt 6):1249-64. Epub 2009 Jan 26. -PubMed

Stucky CL, Dubin AE, Jeske NA, Malin SA, McKemy DD, Story GM. (2009). Roles of transient receptor potential channels in pain. Brain Res Rev. Apr;60(1):2-23. Epub 2008 Dec 31 -PubMed

Daniels, RL, Takashima, Y and McKemy, DD. (2009) The activity of the neuronal cold sensor TRPM8 is regulated by phospholipase C via the phospholipid phosphoinositol-4,5-bisphosphate. J. Biol Chem. Jan 16;284(3):1570-82. Epub 2008 Nov 18. -PubMed

Wang, YY, Chang, RB, Waters, HN, McKemy, DD, and Liman, ER. (2008) The nociceptor ion channel TRPA1 is potentiated and inactivated by permeating calcium ions.
J. Biol Chem.  Nov 21;283(47):32691-703. Epub 2008 Sep 5.
-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

Daniels, RL, and McKemy DD. (2007) Mice left out in the cold: commentary on the phenotype of TRPM8-nulls. Molecular Pain. Aug 17;3(1):23. -PubMed

McKemy DD. (2007) Temperature sensing across species. Pflugers Arch. Aug;454(5):777-91. -PubMed

Jordt, SE, Bautista, DM, Chuang, HH, McKemy, DD, Zygmunt, PM, Hogestatt, ED, Meng, ID, Julius, D (2004) Mustard oils and cannabinoids excite sensory nerve fibres through the TRP channel ANKTM1. Nature. 427: 260-265. -PubMed

Jordt SE, McKemy DD, Julius D (2003) Lessons from peppers and peppermint: the molecular logic of thermosensation. Curr Opin Neurobiol. 13:487-492. -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