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David Julius
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David Julius
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David Jay Julius (born November 4, 1955) is an American physiologist and Nobel Prize laureate known for his work on molecular mechanisms of pain sensation and heat, including the characterization of the TRPV1 and TRPM8 receptors that detect capsaicin, menthol, and temperature. He is a professor at the University of California, San Francisco.

Key Information

Julius won the 2010 Shaw Prize in Life Science and Medicine and the 2020 Breakthrough Prize in Life Sciences.[2][3] In 2020 he was awarded The Kavli Prize,[4] and in 2021 the Nobel Prize in Physiology or Medicine jointly with Ardem Patapoutian.[5]

Early life and education

[edit]

Julius was born to an Ashkenazi Jewish family (from Russia) in Brighton Beach, Brooklyn, New York City,[6] where he attended Abraham Lincoln High School.[7] He earned his undergraduate degree from Massachusetts Institute of Technology in 1977. He attained his doctorate from University of California, Berkeley in 1984, under joint supervision of Jeremy Thorner and Randy Schekman, where he identified Kex2 as the founding member of furin-like proprotein convertases.[8] In 1989, he completed his post-doctoral training with Richard Axel at Columbia University where he cloned and characterized the serotonin 1c receptor.[9]

While at Berkeley and Columbia, Julius became interested in how psilocybin mushrooms and lysergic acid diethylamide work, which led him to look more broadly into how things from nature interact with human receptors.[7]

Research career

[edit]
Nobel Prize work

He started his career as faculty at the University of California, San Francisco in 1989.[10][11] In 1997, Julius's lab cloned and characterized TRPV1 which is the receptor that detects capsaicin, the chemical in chili peppers that makes them "hot".[12] They found that TRPV1 also detects noxious heat (thermoception).[12][13] TRPV1 is part of a large family of structurally related TRP (transient receptor potential) cation channels. Animals that lack TRPV1 (using genetic knockouts of the protein) lose sensitivity to noxious heat and capsaicin.[14]

Julius's lab has also cloned and characterized TRPM8 (CMR1) and TRPA1, both members of the TRP superfamily. They demonstrated that TRPM8 detects menthol and cooler temperatures[15][16] and TRPA1 detects mustard oil (allyl isothiocyanate).[17] These observations suggested that TRP channels detect a range of temperatures and chemicals. David Julius's lab has also made contributions to the study of nociception by discovering toxins that modulate these channels,[18] describing unique adaptations of the channels in diverse species[19] and solving the cryo-EM structures of numerous channels.[20][21]

Julius’ laboratory also made pioneering contributions to the discovery of purinergic receptors, both the P2Y class of G protein-coupled receptors, and the P2X class of ligand-gated ion channels.[22][23] This included the cloning of P2Y12, the receptor for clopidogrel and related antiplatelet medications that are widely used to reduce the risk of heart disease and stroke.[24] The group also cloned the 5HT3 receptor, a serotonin-activated ion channel and the target for drugs such as ondansentron for the treatment of nausea and vomiting.[25]

Julius in 2022

From 2007 to 2020 Julius served as the editor of the peer-reviewed journal the Annual Review of Physiology.[26][27]

Awards

[edit]

In 2000, Julius was awarded the inaugural Perl-UNC Neuroscience Prize for his work on cloning the capsaicin receptor. In 2006, he was honored be The International Prize for Translational Neuroscience of the Max Planck Society.[28] In 2007, Julius received the W. Alden Spencer Award by the College of Physicians and Surgeons, the Department of Neuroscience, and The Kavli Institute for Brain Science at Columbia University, and the Julius Axelrod Prize of the Society for Neuroscience.[29] In 2008, he held the Jack Cooper Lecture at Yale School of Medicine. In 2010, he won the Shaw Prize for his work identifying the ion channels involved in various aspects of nociception. He received the Passano Award in the same year. In 2014, he was honored by Johnson & Johnson with the Dr. Paul Janssen Award for Biomedical Research for discovering the molecular basis for pain and thermosensation. In 2017, he won the Gairdner Foundation International Award[30] and the HFSP Nakasone Award.[31] He has also been awarded the 2010 Prince of Asturias Prize for Technical and Scientific Research, the 2020 Breakthrough Prize in Life Sciences,[32] and the 2020 Kavli Prize in Neuroscience (together with Ardem Patapoutian)[4] and the 2020 BBVA Foundation Frontiers of Knowledge Award.[33]

In 2021, he was awarded the Nobel Prize in Physiology or Medicine jointly with Ardem Patapoutian for their discoveries of receptors for temperature and touch.[34]

In 2022, Julius was awarded the UCSF Medal by the University of California, San Francisco.[35] In 2023, he received the John J. Bonica Award, by the American Society of Regional Anesthesia and Pain Medicine (ASRA).[36] In 2025, Julius was awarded a Honorary Membership in the Society of Toxicology.[37]

See also

[edit]

References

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David Julius

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David Julius (born November 4, 1955) is an American physiologist and renowned for his discoveries elucidating the molecular basis of thermosensation and perception. As the Morris Herzstein Chair in and and chair of the Department of at the (UCSF), Julius has advanced understanding of how sensory neurons detect temperature, touch, and chemical irritants, laying foundational insights for research and therapeutic development. His work, spanning over three decades, has identified key ion channels such as and , which serve as molecular sensors for heat and cold, respectively, and has earned him the 2021 in or , shared with . Born in , New York, to first-generation American parents of Ashkenazi Jewish descent from Eastern Europe, Julius grew up in the neighborhood, a close-knit immigrant community that shaped his early experiences. He attended public schools, including Abraham Lincoln High School, before earning a B.S. in life sciences from the Massachusetts Institute of Technology (MIT) in 1977, where he studied tRNA aminoacylation under Alexander Rich. Julius then pursued a Ph.D. in biochemistry at the , completing it in 1984 under Jeremy Thorner and , focusing on processing in . Following postdoctoral training in neuropharmacology at with from 1984 to 1989, where he developed expression-cloning techniques to identify serotonin receptor genes, he joined the UCSF faculty in 1989. Julius's research has centered on somatosensation, employing natural compounds like from chili peppers and from mint to isolate genes encoding thermosensitive s in sensory neurons. In the late 1990s, his team identified , a heat-activated that responds to and noxious temperatures above 43°C, providing the first molecular explanation for pain signaling from thermal stimuli. Building on this, he discovered as the principal detector of cold temperatures and , and later , activated by irritants like those in wasabi and , advancing knowledge of chemical and mechanical . These findings have illuminated pathways underlying inflammatory pain, hypersensitivity, and potential analgesic targets, influencing drug discovery for conditions like . In addition to the Nobel Prize, Julius has received numerous accolades, including the 2023 John J. Bonica Award, the 2020 in , the 2020 , the 2017 , the 2010 in Life Science and Medicine, and the 2025 Honorary Membership from the Society of Toxicology. He is a member of the and the American Academy of Arts and Sciences, and serves on scientific advisory boards such as the McKnight Endowment Fund for . Married to UCSF colleague Holly Ingraham, Julius continues to lead research at UCSF, emphasizing curiosity-driven supported by public funding like the NIH.

Early life and education

Early life

David Julius was born on November 4, 1955, in , , New York. He was a first-generation American, with his parents being children of Eastern European Jewish immigrants who had fled in Czarist Russia in the early 1900s. His father worked as an electrical engineer, and his mother was an elementary school teacher; both had earned their college degrees from the , emphasizing education and opportunity within their close-knit family of three sons. Julius grew up in the working-class neighborhood, a dense, gritty seaside community near that served as a landing pad for immigrants like his grandparents and was later immortalized in Neil Simon's . The family lived modestly in a small semi-attached house with extended relatives, including his maternal grandmother, aunt, uncle, and cousins, while his paternal grandparents resided nearby. He attended local public elementary schools, where he was initially a reluctant student but began applying greater effort around the fifth grade amid the social upheavals of the and era. The immigrant-rooted household fostered intellectual curiosity through family discussions and the vibrant cultural access of , sparking Julius's early passion for science amid everyday beach activities, pickup , and affordable outings to museums and concerts. As a native New Yorker with a humorous temperament, he drew formative influences from the neighborhood's diverse, resilient environment. This background led him to pursue high school education in , setting the stage for his academic path.

Education

David Julius attended public elementary schools in Brooklyn, New York. He was accepted to , a specialized public school for science and math, but left after his freshman year, finding its intense environment not a good fit as he preferred social activities like . He then transferred to Abraham Lincoln High School in his neighborhood, from which he graduated in 1972. Julius pursued undergraduate studies at the Massachusetts Institute of Technology (MIT) in the 1970s, earning a B.S. degree in life sciences in 1977. During his time at MIT, he engaged in hands-on laboratory experiences that ignited his interest in , including work in Joel Huberman’s laboratory studying and in Alexander Rich’s laboratory investigating kinetics and ribosomal protein synthesis, co-authoring a publication. He then moved to the , where he completed a Ph.D. in biochemistry in 1984. His doctoral thesis focused on the synthesis and secretion of the alpha-factor, including the identification of the KEX2 protease, conducted under the guidance of advisors Jeremy Thorner and .

Professional career

Postdoctoral research

Following the completion of his PhD at the , where he investigated the biochemistry of signaling, David Julius transitioned to postdoctoral training in molecular neurobiology at under from 1984 to 1989. In Axel's laboratory, Julius shifted his focus from microbial biochemistry to neuropharmacology, applying and systems to identify and characterize receptors in mammalian systems. His primary project involved developing a function-based expression cloning strategy using oocytes and mammalian cell lines to isolate cDNAs encoding serotonin receptors from rat brain tissue. This approach enabled the functional screening of receptor activity through electrophysiological recordings and ligand-binding assays, marking a key advancement in studying receptor diversity and signaling. Julius's efforts culminated in the cloning of the serotonin 5-HT1C receptor (now classified as 5-HT2C), a G-protein-coupled receptor prominently expressed in the , with implications for serotonin-mediated modulation of mood and behavior. He demonstrated that ectopic expression of this receptor in non-neuronal cells could trigger activation and, in some cases, , underscoring its role in cellular signaling pathways. These findings, published in high-impact journals, highlighted the receptor's structural and functional conservation within the serotonin family. This postdoctoral phase was marked by significant challenges, including Julius's initial lack of expertise in vertebrate neurophysiology and mammalian , compounded by the competitive nature of receptor efforts. After years of technical hurdles and false starts in library screening and expression optimization, productivity accelerated in the final two years, yielding foundational insights that bridged biophysical assays with genetic approaches to receptor biology.

Faculty positions and leadership

In 1989, David Julius joined the (UCSF) as an in the Department of Cellular and Molecular Pharmacology. His early faculty research built upon postdoctoral work at , shifting focus toward molecular mechanisms of sensory transduction. Julius advanced through the academic ranks at UCSF, becoming a full professor by the early 2000s and serving as vice chair of the Department of Cellular and Molecular Pharmacology prior to 2006. In October 2006, he was appointed chair of the Department of Physiology, a position he continues to hold, overseeing departmental operations, faculty recruitment, and strategic initiatives in physiological research. He also holds the Morris Herzstein Chair in and , recognizing his contributions to the institution. Throughout his tenure, Julius has demonstrated strong in academic governance, including participation in departmental committees and oversight of graduate training programs within the neurosciences and curricula at UCSF. His lab has expanded considerably, supported by sustained funding from the , such as the MERIT Award (R35NS105038) from 2017 to 2025, enabling growth in personnel and research infrastructure. Julius has mentored numerous trainees, including graduate students and postdoctoral fellows from diverse backgrounds, with more than 90% of his lab advancing to independent faculty or roles at prestigious academic and industry institutions.

Scientific research

Discovery of key ion channels

David Julius's laboratory at the (UCSF) pioneered the identification of transient receptor potential (TRP) channels as molecular sensors for environmental stimuli in sensory neurons. In 1997, Julius and colleagues identified as the receptor for , the pungent compound in chili peppers that elicits burning pain sensations. Using expression cloning techniques, the team screened a from neurons in laevis oocytes and human embryonic kidney (HEK) 293 cells, detecting capsaicin-activated currents via and electrophysiological recordings. This approach isolated the vanilloid receptor 1 (VR1, now ), revealing its activation by noxious heat above 43°C, which linked chemical irritants to thermal . Building on this, in 2002, the Julius team discovered as the responsible for detecting cool temperatures and , the cooling agent in mint. Through similar functional expression screening in HEK cells, they identified (initially called CMR1) from a , where application triggered robust calcium influx and inward currents. Functional assays demonstrated 's temperature sensitivity, with activation thresholds below 25–28°C, enabling it to transduce non-noxious cold stimuli into neuronal signals. These findings, published in Nature, established as a key thermosensor, paralleling TRPV1's role in heat detection. Molecular characterization of these channels highlighted their structural and functional properties. forms a tetrameric non-selective cation channel with six transmembrane domains per subunit, exhibiting high permeability to calcium ions (P_Ca/P_Na ≈ 9.6), which underlies its role in depolarizing sensory neurons upon . shares a similar topology but is also non-selective for cations, with notable menthol and icilin sensitivity that shifts its voltage-dependent curve. Genetic validation came from knockout studies: -null mice, generated by targeted disruption in the Julius lab, abolished responses and reduced thermal hyperalgesia in inflammatory models, confirming its necessity for certain pain pathways. Similarly, -deficient mice exhibited profound deficits in cold- and -evoked behaviors, such as reduced nocifensive responses to acetone application on hindpaws. These discoveries emerged from collaborative efforts within the UCSF community, involving electrophysiologists, molecular biologists, and behavioral experts who integrated , , and patch-clamp techniques to characterize channel function. Initial reports in high-impact journals like and not only detailed the and assays but also provided foundational evidence for TRP channels as versatile sensory transducers.

Impact on somatosensation and therapeutics

David Julius's discovery of thermosensitive transient receptor potential (TRP) channels has fundamentally elucidated the molecular mechanisms underlying somatosensation, particularly the detection of temperature and chemical irritants by . , a key channel identified by his team, activates at temperatures above 43°C and in response to , facilitating calcium influx that triggers nociceptive signaling in sensory neurons. This channel integrates multiple stimuli, including protons and inflammatory mediators, which lower its activation threshold during tissue injury, thereby enhancing heat sensitivity. Similarly, detects cold temperatures below 25–28°C and , while responds to chemical irritants like , contributing to the sensory detection of environmental threats and integrating with broader pathways for and irritation signaling. Julius's work has provided critical insights into the pathophysiology of inflammatory and , demonstrating how TRP channels mediate hypersensitivity in these conditions. In animal models, TRPV1 knockout mice exhibit reduced thermal following or , underscoring the channel's role in central sensitization and persistent pain states. These findings have revealed that TRP channels, such as and , are sensitized by endogenous factors like and prostaglandins, linking peripheral sensory transduction to disorders including and . For , TRPM8 activation contributes to cold allodynia, while TRPA1 drives mechanical hypersensitivity, offering a mechanistic framework for understanding pain beyond simple thermal detection. The implications of Julius's research extend to therapeutic advancements in , particularly through targeting TRP channels for non-opioid . Capsaicin-based therapies, such as the 8% dermal patch Qutenza, have been approved for and other neuropathic pains by selectively desensitizing -expressing nociceptors. Earlier antagonists, including compounds like NEO6860 and mavatrep, showed some efficacy in completed phase II trials during the for and inflammatory pain but faced challenges like and lack of endpoint achievement, limiting further development. Ongoing studies explore and modulators for itch and , with preclinical models indicating potential in conditions like and , where channel blockade reduces hypersensitivity without affecting normal sensation. As of 2025, antagonists such as LY3526318 are in phase II trials for indications including diabetic , demonstrating analgesic benefits in proof-of-concept studies. , a potent agonist, is in phase III trials for knee pain (initiated 2022 by ) and showed promising pain reduction and opioid sparing in phase I/II trials for intractable cancer pain as of May 2025. Julius's contributions have catalyzed a paradigm shift in sensory biology, transforming the view of somatosensation from vague neural processes to defined molecular pathways amenable to intervention. Since the early 2000s, research on TRP channels has expanded significantly, with thousands of PubMed publications (over 5,000 for TRP channels and pain as of 2025) exploring their roles in pain and beyond, inspiring thousands of follow-up studies on channel structures via cryo-EM and novel drug screening. This foundational work has influenced global efforts in drug development, emphasizing TRP channels as high-impact targets for addressing the opioid crisis through safer, selective pain relief strategies.

Awards and honors

Nobel Prize in Physiology or Medicine

On October 4, 2021, the Nobel Assembly at Karolinska Institutet announced that the in Physiology or Medicine was awarded jointly to David Julius of the , and of for their discoveries of receptors for temperature and touch. The prize recognized their groundbreaking contributions to understanding the molecular basis of somatosensation, with Julius's work specifically identifying the as a key heat-activated receptor in sensory neurons, using from chili peppers as a probe. Patapoutian's complementary discoveries included mechanosensitive s that respond to touch and pressure, together elucidating how external stimuli like heat, cold, and mechanical force trigger nerve impulses. The total prize amount was 10 million Swedish kronor (SEK), shared equally between the two laureates. Due to the ongoing , the formal award ceremony on December 10, 2021, in Stockholm's City Hall was adapted into a scaled-down event without the laureates' physical presence; Julius received his Nobel medal and diploma during a local ceremony at UCSF. In his Nobel lecture delivered virtually on December 7, 2021, titled "From peppers to peppermints: insights into thermosensation and pain," Julius emphasized the potential of these receptor discoveries to inspire non-opioid pain therapies and reflected on the role of natural products in advancing sensory . The announcement sparked widespread media coverage in outlets such as , , and , highlighting the prize's implications for and . At UCSF, celebrations included a virtual tribute with Sam Hawgood and Dean Talmadge E. King Jr., a champagne toast in Julius's lab, and a rooftop gathering featuring chili pepper-themed decorations, where colleagues applauded his contributions. In personal reflections shared shortly after the announcement, Julius and his family expressed profound shock at the news, with his mother calling it "just unbelievable," and he underscored the value of curiosity-driven research in tackling .

Other major awards

David Julius's scientific contributions began receiving major recognition in the early 2000s, culminating in his election to the in 2004 for his pioneering work on molecular mechanisms of sensory transduction. This honor, one of the highest distinctions in the U.S. scientific community, marked a pivotal point in his career, affirming his rising influence in and pain research. In 2010, Julius received the in Life Science and Medicine for his seminal discoveries of molecular mechanisms by which the skin senses painful stimuli, temperature, and produces pain hypersensitivity, highlighting the foundational impact of his TRP channel research on somatosensation. Building on these achievements, Julius was elected to the in 2012, recognizing his broader contributions to biomedical science and policy. This membership underscored his role in advancing therapeutic insights into pain and sensory disorders. In 2017, he received the for determining the molecular basis of somatosensation, including how humans sense heat, cold, and pain through natural toxins like those from tarantulas and chili peppers, emphasizing the translational potential of his findings. The momentum continued with the 2020 , awarded to Julius for discovering molecules, cells, and mechanisms underlying pain sensation, a $3 million honor that celebrated his group's collaborative efforts in identifying thermosensitive ion channels. In 2020, he shared the in with for their independent discoveries of receptors for temperature and pressure, further validating the transformative role of TRP channels in sensory . These awards, clustered around his TRP channel breakthroughs, propelled Julius's career toward global prominence, influencing pain therapeutics and sensory biology. Post-Nobel recognitions reinforced his enduring impact. In 2023, Julius received the John J. Bonica Award from the for his exceptional contributions to research and , embodying the ideals of advancing multidisciplinary science. Most recently, in 2025, he was awarded Honorary Membership in the for outstanding and sustained achievements in and allied disciplines, particularly his use of natural toxins to probe sensory mechanisms. These honors, spanning academies, international prizes, and specialized societies, illustrate a progression from foundational recognition to field-wide acclaim, with the 2021 serving as a capstone to his pre-existing accolades.

References

  1. https://www.nobelprize.org/prizes/medicine/2021/julius/facts/
  2. https://www.ucsf.edu/news/2021/09/421486/biography-david-julius
  3. https://profiles.ucsf.edu/david.julius
  4. https://www.nobelprize.org/prizes/medicine/2021/julius/biographical/
  5. https://www.jewishvirtuallibrary.org/david-julius
  6. https://asra.com/news-publications/asra-update-item/asra-updates/2023/08/15/dr.-david-julius-receives-the-2023-john-j.-bonica-award
  7. https://www.toxicology.org/about/lnm/honorary-members.asp
  8. https://www.shawprize.org/autobiography/david-julius/
  9. https://digital.sciencehistory.org/works/1fdda3i
  10. https://pmc.ncbi.nlm.nih.gov/articles/PMC11491139/
  11. https://www.kavliprize.org/david-julius-autobiography
  12. https://www.science.org/doi/10.1126/science.3399891
  13. https://www.cell.com/neuron/fulltext/S0896-6273%2822%2900100-3
  14. https://www.science.org/doi/10.1126/science.2727693
  15. https://www.ucsf.edu/news/2006/10/97915/expert-pain-sensation-named-ucsf-physiology-chair
  16. https://physiology.ucsf.edu/content/julius-david-phd
  17. https://www.cell-symposia.com/neuroimmunology-2025/bio-DavidJulius.html
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  22. https://pmc.ncbi.nlm.nih.gov/articles/PMC4843893/
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  26. https://www.nih.gov/news-events/news-releases/nih-scientists-pioneer-promising-treatment-intractable-cancer-pain
  27. https://www.cell.com/cell/fulltext/S0092-8674(21)01384-2
  28. https://www.nobelprize.org/prizes/medicine/2021/press-release/
  29. https://apnews.com/article/coronavirus-pandemic-entertainment-science-health-arts-and-entertainment-2c48ceb4dbcb122a44f75a002a677d5a
  30. https://www.nobelprize.org/prizes/medicine/2021/julius/lecture/
  31. https://www.ucsf.edu/news/2021/10/421571/ucsf-celebrates-its-newest-nobel-laureate-david-julius
  32. https://www.nobelprize.org/prizes/medicine/2021/julius/interview/
  33. https://www.kavliprize.org/bio/David-julius
  34. https://www.shawprize.org/laureates/2010-life-science-medicine/
  35. https://www.gairdner.org/winner/david-julius
  36. https://breakthroughprize.org/Laureates/2/L3868
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