David McKemy

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

Tenure Track Appointments

• Professor of Biological Sciences, University of Southern California , 12/05/2018 –
• Associate Professor, University of Southern California, 04/19/2011 – 12/04/2018
• Assistant Professor, University of Southern California, 01/04/2004 – 04/18/2011

PostDoctoral Appointments

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

Summary Statement of Research Interests

The laboratory is interested in the neurobiological basis 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 afferent neurons are the principal sensors of these stimuli and convert discrete environmental cues into neural responses that convey these distinct percepts. They are also key in chronic pain produced with injury and disease.

Using a combination of molecular, cellular, genetic, electrophysiological, and biochemical approaches we wish to identify the molecules and cellular processes that produce these debilitating conditions.

It is our hope that these studies will provide insights into the mechanisms that lead to inflammatory and neuropathic pain, thereby leading to the identification of new targets for the development of novel therapeutic approaches to treat such as various ailments such as chronic pain and migraine.

Research Keywords

Somatosensation, Pain, TRP channels, Thermosensation, migraine

Book Chapters

• McKemy,McKemy,McKemy, D. D. (2018). Molecular basis of peripheral innocuous cold sensitivity. (Vol. 156) pp. 57-67. Handbook of clinical neurology. PubMed Web Address

Journal Article

• Yang, C., Wei, C., Alam, S., Chen, X., McKemy,Yang, D. D., Wei, C., Alam, S., Chen, X., McKemy,Yang, D. D., Wei, C., Alam, S., Chen, X., McKemy,Yang, D. D., Wei, C., Alam, S., Chen, X., McKemy, D. D. (2024). The neurotrophic factor artemin and its receptor GFRα3 mediate migraine-like pain via the ion channel TRPM8. Cephalalgia : an international journal of headache. Vol. 44 (11), pp. 3331024241297679. PubMed Web Address
• Yang, C., Yamaki, S., Jung, T., Kim, B., Huyhn, R., McKemy,Yang, D. D., Yamaki, S., Jung, T., Kim, B., Huyhn, R., McKemy,Yang, D. D., Yamaki, S., Jung, T., Kim, B., Huyhn, R., McKemy,Yang, D. D., Yamaki, S., Jung, T., Kim, B., Huyhn, R., McKemy, D. D. (2023). Endogenous Inflammatory Mediators Produced by Injury Activate TRPV1 and TRPA1 Nociceptors to Induce Sexually Dimorphic Cold Pain That Is Dependent on TRPM8 and GFRα3. The Journal of neuroscience : the official journal of the Society for Neuroscience. Vol. 43 (15), pp. 2803-2814. PubMed Web Address
• Wei, C., Kim, B., McKemy,Wei, D. D., Kim, B., McKemy,Wei, D. D., Kim, B., McKemy, D. D. (2022). Transient receptor potential melastatin 8 is required for nitroglycerin- and calcitonin gene-related peptide-induced migraine-like pain behaviors in mice. Pain. Vol. 163 (12), pp. 2380-2389. PubMed Web Address
• Jeong, S. L., Zhang, H., Yamaki, S., Yang, C., McKemy, D. D., Lieber, M. R., Pham, P., Goodman,Jeong, M. F., Zhang, H., Yamaki, S., Yang, C., McKemy, D. D., Lieber, M. R., Pham, P., Goodman,Jeong, M. F., Zhang, H., Yamaki, S., Yang, C., McKemy, D. D., Lieber, M. R., Pham, P., Goodman, M. F. (2022). Immunoglobulin somatic hypermutation in a defined biochemical system recapitulates affinity maturation and permits antibody optimization. Nucleic acids research. Vol. 50 (20), pp. 11738-11754. PubMed Web Address
• Yamaki, S., Chau, A., Gonzales, L., McKemy,Yamaki, D. D., Chau, A., Gonzales, L., McKemy,Yamaki, D. D., Chau, A., Gonzales, L., McKemy, D. D. (2021). Nociceptive afferent phenotyping reveals that transient receptor potential ankyrin 1 promotes cold pain through neurogenic inflammation upstream of the neurotrophic factor receptor GFRα3 and the menthol receptor transient receptor potential melastatin 8. Pain. Vol. 162 (2), pp. 609-618. PubMed Web Address
• Palkar, R., Ongun, S., Catich, E., Li, N., Borad, N., Sarkisian, A., McKemy,Palkar, D. D., Ongun, S., Catich, E., Li, N., Borad, N., Sarkisian, A., McKemy,Palkar, D. D., Ongun, S., Catich, E., Li, N., Borad, N., Sarkisian, A., McKemy, D. D. (2018). Cooling Relief of Acute and Chronic Itch Requires TRPM8 Channels and Neurons. The Journal of investigative dermatology. Vol. 138 (6), pp. 1391-1399. PubMed Web Address
• Ongun, S., Sarkisian, A., McKemy,Ongun, D. D., Sarkisian, A., McKemy,Ongun, D. D., Sarkisian, A., McKemy, D. D. (2018). Selective cold pain inhibition by targeted block of TRPM8-expressing neurons with quaternary lidocaine derivative QX-314. Communications biology. Vol. 1, pp. 53. PubMed Web Address
• McCoy, D. D., Palkar, R., Yang, Y., Ongun, S., McKemy,McCoy, D. D., Palkar, R., Yang, Y., Ongun, S., McKemy,McCoy, D. D., Palkar, R., Yang, Y., Ongun, S., McKemy, D. D. (2017). Cellular permeation of large molecules mediated by TRPM8 channels. Neuroscience letters. Vol. 639, pp. 59-67. PubMed Web Address
• Lippoldt, E. K., Ongun, S., Kusaka, G. K., McKemy,Lippoldt, D. D., Ongun, S., Kusaka, G. K., McKemy,Lippoldt, D. D., Ongun, S., Kusaka, G. K., McKemy, D. D. (2016). Inflammatory and neuropathic cold allodynia are selectively mediated by the neurotrophic factor receptor GFRα3. Proceedings of the National Academy of Sciences of the United States of America. Vol. 113 (16), pp. 4506-11. PubMed Web Address
• Palkar, R., Lippoldt, E. K., McKemy,Palkar, D. D., Lippoldt, E. K., McKemy,Palkar, D. D., Lippoldt, E. K., McKemy, D. D. (2015). The molecular and cellular basis of thermosensation in mammals. Current opinion in neurobiology. Vol. 34, pp. 14-9. PubMed Web Address
• von, H. C., Mei, F., Greenfield, A., Jahn, S., Shen, Y. A., Reid, H. H., McKemy, D. D., Chan,von, J. R., Mei, F., Greenfield, A., Jahn, S., Shen, Y. A., Reid, H. H., McKemy, D. D., Chan,von, J. R., Mei, F., Greenfield, A., Jahn, S., Shen, Y. A., Reid, H. H., McKemy, D. D., Chan, J. R. (2015). The myelin oligodendrocyte glycoprotein directly binds nerve growth factor to modulate central axon circuitry. The Journal of cell biology. Vol. 210 (6), pp. 891-8. PubMed Web Address
• Kim, Y. S., Park, J. H., Choi, S. J., Bae, J. Y., Ahn, D. K., McKemy, D. D., Bae,Kim, Y. C., Park, J. H., Choi, S. J., Bae, J. Y., Ahn, D. K., McKemy, D. D., Bae,Kim, Y. C., 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. Vol. 9 (4), pp. e94080. PubMed Web Address
• Lippoldt, E. K., Elmes, R. R., McCoy, D. D., Knowlton, W. M., McKemy,Lippoldt, D. D., Elmes, R. R., McCoy, D. D., Knowlton, W. M., McKemy,Lippoldt, D. D., Elmes, R. R., McCoy, D. D., Knowlton, W. M., McKemy, D. D. (2013). Artemin, a glial cell line-derived neurotrophic factor family member, induces TRPM8-dependent cold pain. The Journal of neuroscience : the official journal of the Society for Neuroscience. Vol. 33 (30), pp. 12543-52. PubMed Web Address
• 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
• McKemy,McKemy,McKemy, D. D. (2011). A spicy family tree: TRPV1 and its thermoceptive and nociceptive lineage. The EMBO journal. Vol. 30 (3), pp. 453-5. 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

Editorships and Editorial Boards

• Reviewing Editor, Journal of Neuroscience, 2021 –
• Editorial Board, The Open Drug Discovery Journal, 2009 – 2021

Professional Memberships

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