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Neuroscience Graduate Program at UCSF

Faculty - David Julius, Ph.D.

The Molecular Biology of Nociception and Pain


Research Description

We are interested in the molecular biology of sensory transduction and neurotransmitter action in the mammalian nervous system. A main goal is to understand the molecular basis of somatosensation - the process whereby we experience touch and temperature - with an emphasis on identifying molecules that detect noxious (pain-producing) stimuli. We are also interested in understanding how somatosensation is altered in response to tissue or nerve injury.

Our approach has been to identify molecular targets for natural plant products that mimic the psychophysical effects of commonly encountered somatosensory stimuli, such as heat, cold, or chemical irritants. This has led us to uncover ion channels belonging to the TRP channel family that serve as receptors for capsaicin (from chili peppers), menthol (from mint) or isothiocyanates and thiosulfinates (from wasabi and garlic), all of which activate nerve fibers of the somatosensory system to elicit sensations of hot, cold, and/or irritancy, respectively. We explore the functional, structural, and physiological properties of these sensory TRP channel in vitro and in vivo using biophysical, genetic, and pharmacologic approaches. We also use a variety of gene discovery methods to identify new players in the cellular signaling pathways that detect, transduce, and modulate somatosensory stimuli, including those that contribute to acute and chronic pain.

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Current Projects

See above.

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Lab Members

Erhu Cao, Postdoctoral Fellow
Julio Cordero, Postdoctoral Fellow
Joshua Emrick, Graduate Student (DDS/PhD Program)
Yuan Gao, Graduate Student (Biophysics)
Duncan Leitch, Postdoctoral Fellow
Jeremiah Osteen, Postdoctoral Fellow
Candice Paulsen, Postdoctoral Fellow
Chuchu Zhang, Graduate Student (Neuroscience)
Jeannie Poblete, Laboratory Manager
Lissette Irizarry, Administrative Assistant

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Selected Publications

Link to Publication via PubMed

Caterina M, Schumacher M, Tominaga M, Rosen T, Levine J, and Julius D (l997) The Capsaicin Receptor:
A Heat-Activated Ion Channel in the Pain Pathway. Nature 389: 816-824

Caterina M, Leffler A, Malmberg A, Martin W, Trafton J, Petersen-Zeitz K, Koltzenburg M, Basbaum A,
and Julius D (2000) Impaired Nociception and Pain Sensation in Mice Lacking the Capsaicin Receptor.
Science 288: 306-313

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

Bautista D, Jordt S, Nikai T, Tsuruda P, Read A, Poblete J, Yamoah E, Basbaum A and Julius D (2006)
TRPA1 mediates the inflammatory action of environmental irritants and proalgesic agents. Cell 124: 1269–
1282

Bautista D, Siemens J, Glazer J, Tsuruda P, Basbaum A, Stucky C, Jordt S and Julius D (2007) The menthol
receptor TRPM8 is the principal detector of environmental cold. Nature 448: 204-209

Basbaum AI, Bautista DM, Scherrer G and Julius D (2009) Cellular and molecular mechanisms of pain
(Leading Edge Review). Cell 139: 267-284

Gracheva EO, Ingolia NT, Kelly YM, Cordero-Morales JF, Hollopeter G, Chesler AT, Sánchez EE, Perez
JC, Weissman JS and Julius D (2010) Molecular basis of infrared detection by snakes. Nature 464: 1006-
1011

Bohlen CJ, Priel A, Zhou S, King D, Siemens J and Julius D (2010) A bivalent tarantula toxin activates the
capsaicin receptor, TRPV1, by targeting the outer pore domain. Cell 141: 834-845

Cao E, Cordero-Morales JF, Liu B, Qin F and Julius D (2013) TRPV1 channels are intrinsically heat
sensitive and negatively regulated by phosphoinositide lipids. Neuron 77: 667-679

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David Julius, Ph.D.



Email

david.julius@ucsf.edu

Phone

415-476-0431

Office Address

UCSF MC 2140
Genentech Hall
600 16th Street, N-272E
San Francisco, CA 94143-2140

Other Websites

Biomedical Sciences Graduate Program

Lab Website

PIBS Website

TETRAD

The Wheeler Center for the Neurobiology of Addiction