David Julius, PhD

Chair and Professor
Physiology
+1 415 476-0431

Our group is interested in understanding how sensory systems enable us to perceive our world. In one aspect of our research, we exploit the power of natural products to elucidate molecular mechanisms of touch and pain sensation. For example, we have asked how capsaicin, the main pungent ingredient in "hot" chili peppers, elicits burning pain, and how menthol, the cooling agent in mint leaves, evokes an icy cool sensation. Using these and other agents as pharmacological probes, we have identified ion channels on sensory nerve fibers that are activated by heat, cold, or chemical irritants, providing molecular insight into the process of thermosensation, pain, and itch. With the aid of genetic, electrophysiological, structural, and behavioral methods, we are asking how these ion channels are modulated in response to tumor growth, infection, or other forms of injury that produce inflammation and pain hypersensitivity. These basic scientific studies are helping to lay a foundation for the discovery and development of novel analgesic drugs.

Publications: 

Structural basis of TRPV1 modulation by endogenous bioactive lipids.

Nature structural & molecular biology

Arnold WR, Mancino A, Moss FR, Frost A, Julius D, Cheng Y

Crypt and Villus Enterochromaffin Cells are Distinct Stress Sensors in the Gut.

bioRxiv : the preprint server for biology

Touhara KK, Rossen ND, Deng F, Chu T, Cil O, Li Y, Julius D

Neuroendocrine cells initiate protective upper airway reflexes.

Science (New York, N.Y.)

Seeholzer LF, Julius D

Allosteric regulation of TRPV1 by the inflammatory lipid LPA.

bioRxiv : the preprint server for biology

Arnold WR, Julius D, Cheng Y

Endogenous Opioid Signaling Regulates Proliferation of Spinal Cord Ependymal Cells.

bioRxiv : the preprint server for biology

Yue WWS, Touhara KK, Toma K, Duan X, Julius D

Gut enterochromaffin cells drive visceral pain and anxiety.

Nature

Bayrer JR, Castro J, Venkataraman A, Touhara KK, Rossen ND, Morrie RD, Maddern J, Hendry A, Braverman KN, Garcia-Caraballo S, Schober G, Brizuela M, Castro Navarro FM, Bueno-Silva C, Ingraham HA, Brierley SM, Julius D

Sensory TRP Channels in Three Dimensions.

Annual review of biochemistry

Diver MM, Lin King JV, Julius D, Cheng Y

Irritant-evoked activation and calcium modulation of the TRPA1 receptor.

Nature

Zhao J, Lin King JV, Paulsen CE, Cheng Y, Julius D

Structural insights into TRPM8 inhibition and desensitization.

Science (New York, N.Y.)

Diver MM, Cheng Y, Julius D

A Cell-Penetrating Scorpion Toxin Enables Mode-Specific Modulation of TRPA1 and Pain.

Cell

Lin King JV, Emrick JJ, Kelly MJS, Herzig V, King GF, Medzihradszky KF, Julius D

Membrane mimetic systems in CryoEM: keeping membrane proteins in their native environment.

Current opinion in structural biology

Autzen HE, Julius D, Cheng Y

Structural insight into TRPV5 channel function and modulation.

Proceedings of the National Academy of Sciences of the United States of America

Dang S, van Goor MK, Asarnow D, Wang Y, Julius D, Cheng Y, van der Wijst J

Tissue-specific contributions of Tmem79 to atopic dermatitis and mast cell-mediated histaminergic itch.

Proceedings of the National Academy of Sciences of the United States of America

Emrick JJ, Mathur A, Wei J, Gracheva EO, Gronert K, Rosenblum MD, Julius D

Molecular tuning of electroreception in sharks and skates.

Nature

Bellono NW, Leitch DB, Julius D

Structure of the human TRPM4 ion channel in a lipid nanodisc.

Science (New York, N.Y.)

Autzen HE, Myasnikov AG, Campbell MG, Asarnow D, Julius D, Cheng Y

Enterochromaffin Cells Are Gut Chemosensors that Couple to Sensory Neural Pathways.

Cell

Bellono NW, Bayrer JR, Leitch DB, Castro J, Zhang C, O'Donnell TA, Brierley SM, Ingraham HA, Julius D

Pharmacology of the Nav1.1 domain IV voltage sensor reveals coupling between inactivation gating processes.

Proceedings of the National Academy of Sciences of the United States of America

Osteen JD, Sampson K, Iyer V, Julius D, Bosmans F

Lys49 myotoxin from the Brazilian lancehead pit viper elicits pain through regulated ATP release.

Proceedings of the National Academy of Sciences of the United States of America

Zhang C, Medzihradszky KF, Sánchez EE, Basbaum AI, Julius D

Molecular basis of ancestral vertebrate electroreception.

Nature

Bellono NW, Leitch DB, Julius D

Selective spider toxins reveal a role for the Nav1.1 channel in mechanical pain.

Nature

Osteen JD, Herzig V, Gilchrist J, Emrick JJ, Zhang C, Wang X, Castro J, Garcia-Caraballo S, Grundy L, Rychkov GY, Weyer AD, Dekan Z, Undheim EA, Alewood P, Stucky CL, Brierley SM, Basbaum AI, Bosmans F, King GF, Julius D

Structure of the TRPA1 ion channel suggests regulatory mechanisms.

Nature

Paulsen CE, Armache JP, Gao Y, Cheng Y, Julius D

Editorial overview: molecular biology of sensation.

Current opinion in neurobiology

Julius D, Carlson JR

Structure of the TRPA1 ion channel suggests regulatory mechanisms.

Nature

Paulsen CE, Armache JP, Gao Y, Cheng Y, Julius D

Single particle electron cryo-microscopy of a mammalian ion channel.

Current opinion in structural biology

Liao M, Cao E, Julius D, Cheng Y

TRP channels and pain.

Annual review of cell and developmental biology

Julius D

Receptor-targeting mechanisms of pain-causing toxins: How ow?

Toxicon : official journal of the International Society on Toxinology

Bohlen CJ, Julius D

Signaling by sensory receptors.

Cold Spring Harbor perspectives in biology

Julius D, Nathans J

A heteromeric Texas coral snake toxin targets acid-sensing ion channels to produce pain.

Nature

Bohlen CJ, Chesler AT, Sharif-Naeini R, Medzihradszky KF, Zhou S, King D, S?nchez EE, Burlingame AL, Basbaum AI, Julius D

Cytoplasmic ankyrin repeats of transient receptor potential A1 (TRPA1) dictate sensitivity to thermal and chemical stimuli.

Proceedings of the National Academy of Sciences of the United States of America

Cordero-Morales JF, Gracheva EO, Julius D

Ganglion-specific splicing of TRPV1 underlies infrared sensation in vampire bats.

Nature

Gracheva EO, Cordero-Morales JF, Gonz?lez-Carcac?a JA, Ingolia NT, Manno C, Aranguren CI, Weissman JS, Julius D

Restriction of transient receptor potential vanilloid-1 to the peptidergic subset of primary afferent neurons follows its developmental downregulation in nonpeptidergic neurons.

The Journal of neuroscience : the official journal of the Society for Neuroscience

Cavanaugh DJ, Chesler AT, Br?z JM, Shah NM, Julius D, Basbaum AI

Trpv1 reporter mice reveal highly restricted brain distribution and functional expression in arteriolar smooth muscle cells.

The Journal of neuroscience : the official journal of the Society for Neuroscience

Cavanaugh DJ, Chesler AT, Jackson AC, Sigal YM, Yamanaka H, Grant R, O'Donnell D, Nicoll RA, Shah NM, Julius D, Basbaum AI

Molecular basis of infrared detection by snakes.

Nature

Gracheva EO, Ingolia NT, Kelly YM, Cordero-Morales JF, Hollopeter G, Chesler AT, S?nchez EE, Perez JC, Weissman JS, Julius D

Cellular and molecular mechanisms of pain.

Cell

Basbaum AI, Bautista DM, Scherrer G, Julius D

Radial stretch reveals distinct populations of mechanosensitive mammalian somatosensory neurons.

Proceedings of the National Academy of Sciences of the United States of America

Bhattacharya MR, Bautista DM, Wu K, Haeberle H, Lumpkin EA, Julius D

Multiple unbiased prospective screens identify TRP channels and their conserved gating elements.

The Journal of general physiology

Myers BR, Saimi Y, Julius D, Kung C

Zebrafish TRPA1 channels are required for chemosensation but not for thermosensation or mechanosensory hair cell function.

The Journal of neuroscience : the official journal of the Society for Neuroscience

Prober DA, Zimmerman S, Myers BR, McDermott BM, Kim SH, Caron S, Rihel J, Solnica-Krezel L, Julius D, Hudspeth AJ, Schier AF

Pungent agents from Szechuan peppers excite sensory neurons by inhibiting two-pore potassium channels.

Nature neuroscience

Bautista DM, Sigal YM, Milstein AD, Garrison JL, Zorn JA, Tsuruda PR, Nicoll RA, Julius D

TRPA1 mediates formalin-induced pain.

Proceedings of the National Academy of Sciences of the United States of America

McNamara CR, Mandel-Brehm J, Bautista DM, Siemens J, Deranian KL, Zhao M, Hayward NJ, Chong JA, Julius D, Moran MM, Fanger CM

4-Hydroxynonenal, an endogenous aldehyde, causes pain and neurogenic inflammation through activation of the irritant receptor TRPA1.

Proceedings of the National Academy of Sciences of the United States of America

Trevisani M, Siemens J, Materazzi S, Bautista DM, Nassini R, Campi B, Imamachi N, Andrè E, Patacchini R, Cottrell GS, Gatti R, Basbaum AI, Bunnett NW, Julius D, Geppetti P

The menthol receptor TRPM8 is the principal detector of environmental cold.

Nature

Bautista DM, Siemens J, Glazer JM, Tsuruda PR, Basbaum AI, Stucky CL, Jordt SE, Julius D

TRP channel activation by reversible covalent modification.

Proceedings of the National Academy of Sciences of the United States of America

Hinman A, Chuang HH, Bautista DM, Julius D

The P2Y12 receptor regulates microglial activation by extracellular nucleotides.

Nature neuroscience

Haynes SE, Hollopeter G, Yang G, Kurpius D, Dailey ME, Gan WB, Julius D

Spider toxins activate the capsaicin receptor to produce inflammatory pain.

Nature

Siemens J, Zhou S, Piskorowski R, Nikai T, Lumpkin EA, Basbaum AI, King D, Julius D

Neuroanatomical evidence for segregation of nerve fibers conveying light touch and pain sensation in Eimer's organ of the mole.

Proceedings of the National Academy of Sciences of the United States of America

Marasco PD, Tsuruda PR, Bautista DM, Julius D, Catania KC

Toward better pain control.

Scientific American

Basbaum AI, Julius D

TRPA1 mediates the inflammatory actions of environmental irritants and proalgesic agents.

Cell

Bautista DM, Jordt SE, Nikai T, Tsuruda PR, Read AJ, Poblete J, Yamoah EN, Basbaum AI, Julius D

Pungent products from garlic activate the sensory ion channel TRPA1.

Proceedings of the National Academy of Sciences of the United States of America

Bautista DM, Movahed P, Hinman A, Axelsson HE, Sterner O, Högestätt ED, Julius D, Jordt SE, Zygmunt PM

Selective blockade of the capsaicin receptor TRPV1 attenuates bone cancer pain.

The Journal of neuroscience : the official journal of the Society for Neuroscience

Ghilardi JR, Röhrich H, Lindsay TH, Sevcik MA, Schwei MJ, Kubota K, Halvorson KG, Poblete J, Chaplan SR, Dubin AE, Carruthers NI, Swanson D, Kuskowski M, Flores CM, Julius D, Mantyh PW

A Nobel for smell.

Cell

Julius D, Katz LC

Uropathic observations in mice expressing a constitutively active point mutation in the 5-HT3A receptor subunit.

The Journal of neuroscience : the official journal of the Society for Neuroscience

Bhattacharya A, Dang H, Zhu QM, Schnegelsberg B, Rozengurt N, Cain G, Prantil R, Vorp DA, Guy N, Julius D, Ford AP, Lester HA, Cockayne DA

Changes in anxiety-related behaviors and hypothalamic-pituitary-adrenal activity in mice lacking the 5-HT-3A receptor.

Physiology & behavior

Bhatnagar S, Sun LM, Raber J, Maren S, Julius D, Dallman MF

Immunoreactive TRPV-2 (VRL-1), a capsaicin receptor homolog, in the spinal cord of the rat.

The Journal of comparative neurology

Lewinter RD, Skinner K, Julius D, Basbaum AI

Mustard oils and cannabinoids excite sensory nerve fibres through the TRP channel ANKTM1.

Nature

Jordt SE, Bautista DM, Chuang HH, McKemy DD, Zygmunt PM, Högestätt ED, Meng ID, Julius D

International Union of Pharmacology. XLIII. Compendium of voltage-gated ion channels: transient receptor potential channels.

Pharmacological reviews

Clapham DE, Montell C, Schultz G, Julius D, International Union of Pharmacology

Lessons from peppers and peppermint: the molecular logic of thermosensation.

Current opinion in neurobiology

Jordt SE, McKemy DD, Julius D

A unified nomenclature for the superfamily of TRP cation channels.

Molecular cell

Montell C, Birnbaumer L, Flockerzi V, Bindels RJ, Bruford EA, Caterina MJ, Clapham DE, Harteneck C, Heller S, Julius D, Kojima I, Mori Y, Penner R, Prawitt D, Scharenberg AM, Schultz G, Shimizu N, Zhu MX

The 5-HT3 subtype of serotonin receptor contributes to nociceptive processing via a novel subset of myelinated and unmyelinated nociceptors.

The Journal of neuroscience : the official journal of the Society for Neuroscience

Zeitz KP, Guy N, Malmberg AB, Dirajlal S, Martin WJ, Sun L, Bonhaus DW, Stucky CL, Julius D, Basbaum AI

Molecular mechanisms of nociception.

Nature

Julius D, Basbaum AI

ATP transduces signals from ASGM1, a glycolipid that functions as a bacterial receptor.

Proceedings of the National Academy of Sciences of the United States of America

McNamara N, Khong A, McKemy D, Caterina M, Boyer J, Julius D, Basbaum C

Bradykinin and nerve growth factor release the capsaicin receptor from PtdIns(4,5)P2-mediated inhibition.

Nature

Chuang HH, Prescott ED, Kong H, Shields S, Jordt SE, Basbaum AI, Chao MV, Julius D

Identification of the platelet ADP receptor targeted by antithrombotic drugs.

Nature

Hollopeter G, Jantzen HM, Vincent D, Li G, England L, Ramakrishnan V, Yang RB, Nurden P, Nurden A, Julius D, Conley PB

The vanilloid receptor: a molecular gateway to the pain pathway.

Annual review of neuroscience

Caterina MJ, Julius D

Acid potentiation of the capsaicin receptor determined by a key extracellular site.

Proceedings of the National Academy of Sciences of the United States of America

Jordt SE, Tominaga M, Julius D

Capsaicin receptor in the pain pathway.

Japanese journal of pharmacology

Tominaga M, Julius D

Impaired nociception and pain sensation in mice lacking the capsaicin receptor.

Science (New York, N.Y.)

Caterina MJ, Leffler A, Malmberg AB, Martin WJ, Trafton J, Petersen-Zeitz KR, Koltzenburg M, Basbaum AI, Julius D

Sense and specificity: a molecular identity for nociceptors.

Current opinion in neurobiology

Caterina MJ, Julius D

Unsaturated long-chain N-acyl-vanillyl-amides (N-AVAMs): vanilloid receptor ligands that inhibit anandamide-facilitated transport and bind to CB1 cannabinoid receptors.

Biochemical and biophysical research communications

Melck D, Bisogno T, De Petrocellis L, Chuang H, Julius D, Bifulco M, Di Marzo V

Vanilloid receptors on sensory nerves mediate the vasodilator action of anandamide.

Nature

Zygmunt PM, Petersson J, Andersson DA, Chuang H, Sørgård M, Di Marzo V, Julius D, Högestätt ED

A capsaicin-receptor homologue with a high threshold for noxious heat.

Nature

Caterina MJ, Rosen TA, Tominaga M, Brake AJ, Julius D

Serotonin receptor knockouts: a moody subject.

Proceedings of the National Academy of Sciences of the United States of America

Julius D

The cloned capsaicin receptor integrates multiple pain-producing stimuli.

Neuron

Tominaga M, Caterina MJ, Malmberg AB, Rosen TA, Gilbert H, Skinner K, Raumann BE, Basbaum AI, Julius D

Neuronal expression of the 5HT3 serotonin receptor gene requires nuclear factor 1 complexes.

The Journal of neuroscience : the official journal of the Society for Neuroscience

Bedford FK, Julius D, Ingraham HA

Inactivation of a serotonin-gated ion channel by a polypeptide toxin from marine snails.

Science (New York, N.Y.)

England LJ, Imperial J, Jacobsen R, Craig AG, Gulyas J, Akhtar M, Rivier J, Julius D, Olivera BM

The capsaicin receptor: a heat-activated ion channel in the pain pathway.

Nature

Caterina MJ, Schumacher MA, Tominaga M, Rosen TA, Levine JD, Julius D

ATP receptors in sickness, pain and death.

Chemistry & biology

Brake A, Schumacher M, Julius D

Signaling by extracellular nucleotides.

Annual review of cell and developmental biology

Brake AJ, Julius D

Eating disorder and epilepsy in mice lacking 5-HT2c serotonin receptors.

Nature

Tecott LH, Sun LM, Akana SF, Strack AM, Lowenstein DH, Dallman MF, Julius D

Expression of a serotonin-gated ion channel in embryonic neural and nonneural tissues.

Molecular and cellular neurosciences

Tecott L, Shtrom S, Julius D

A new wave of serotonin receptors.

Current opinion in neurobiology

Tecott LH, Julius D

Expression cloning of an ATP receptor from mouse neuroblastoma cells.

Proceedings of the National Academy of Sciences of the United States of America

Lustig KD, Shiau AK, Brake AJ, Julius D

Nervous system distribution of the serotonin 5-HT3 receptor mRNA.

Proceedings of the National Academy of Sciences of the United States of America

Tecott LH, Maricq AV, Julius D

Serotonin receptor 1c gene assigned to X chromosome in human (band q24) and mouse (bands D-F4).

Human molecular genetics

Milatovich A, Hsieh CL, Bonaminio G, Tecott L, Julius D, Francke U

Primary structure and functional expression of the 5HT3 receptor, a serotonin-gated ion channel.

Science (New York, N.Y.)

Maricq AV, Peterson AS, Brake AJ, Myers RM, Julius D

Molecular biology of serotonin receptors.

Annual review of neuroscience

Julius D

The serotonin receptor subtype 2 locus HTR2 is on human chromosome 13 near genes for esterase D and retinoblastoma-1 and on mouse chromosome 14.

Somatic cell and molecular genetics

Hsieh CL, Bowcock AM, Farrer LA, Hebert JM, Huang KN, Cavalli-Sforza LL, Julius D, Francke U

The 5HT2 receptor defines a family of structurally distinct but functionally conserved serotonin receptors.

Proceedings of the National Academy of Sciences of the United States of America

Julius D, Huang KN, Livelli TJ, Axel R, Jessell TM

5-HT1c receptor is a prominent serotonin receptor subtype in the central nervous system.

Proceedings of the National Academy of Sciences of the United States of America

Molineaux SM, Jessell TM, Axel R, Julius D

Ectopic expression of the serotonin 1c receptor and the triggering of malignant transformation.

Science (New York, N.Y.)

Julius D, Livelli TJ, Jessell TM, Axel R

Molecular characterization of a functional cDNA encoding the serotonin 1c receptor.

Science (New York, N.Y.)

Julius D, MacDermott AB, Axel R, Jessell TM

Functional expression of the 5-HT1c receptor in neuronal and nonneuronal cells.

Cold Spring Harbor symposia on quantitative biology

Julius D, MacDermott AB, Jessel TM, Huang K, Molineaux S, Schieren I, Axel R

Research Area: 
Adipocyte and Metabolism
Central Regulation