David Julius

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David Julius
Dr David Julius by christopher michel in 2022 04 (cropped2).jpg
Julius in 2022
Born (1955-11-04) November 4, 1955 (age 68)
New York City, U.S.
Education Massachusetts Institute of Technology (BS)
University of California, Berkeley (MS, PhD)
Columbia University (post-doctoral training)
Spouse Holly Ingraham
Awards
Scientific career
Fields Physiology
Biochemistry
Neuroscience
Institutions University of California, San Francisco
Thesis Protein processing and secretion in yeast: biosynthesis of α-factor mating pheromone  (1984)
Doctoral advisor Jeremy Thorner
Randy Schekman
Other academic advisors Richard Axel [1]
Alexander Rich

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.

Contents

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

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

Nobel Prize work 22 Hegasy EN Nobel Prize 2021 TRPV1 Piezo2.png
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 Dr David Julius by christopher michel in 2022 08.jpg
Julius in 2022

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

Awards

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]

See also

Related Research Articles

In physiology, thermoception or thermoreception is the sensation and perception of temperature, or more accurately, temperature differences inferred from heat flux. It deals with a series of events and processes required for an organism to receive a temperature stimulus, convert it to a molecular signal, and recognize and characterize the signal in order to trigger an appropriate defense response.

<span class="mw-page-title-main">Thermoreceptor</span> Receptive portion of a sensory neuron

A thermoreceptor is a non-specialised sense receptor, or more accurately the receptive portion of a sensory neuron, that codes absolute and relative changes in temperature, primarily within the innocuous range. In the mammalian peripheral nervous system, warmth receptors are thought to be unmyelinated C-fibres, while those responding to cold have both C-fibers and thinly myelinated A delta fibers. The adequate stimulus for a warm receptor is warming, which results in an increase in their action potential discharge rate. Cooling results in a decrease in warm receptor discharge rate. For cold receptors their firing rate increases during cooling and decreases during warming. Some cold receptors also respond with a brief action potential discharge to high temperatures, i.e. typically above 45 °C, and this is known as a paradoxical response to heat. The mechanism responsible for this behavior has not been determined.

Transient receptor potential channels are a group of ion channels located mostly on the plasma membrane of numerous animal cell types. Most of these are grouped into two broad groups: Group 1 includes TRPC, TRPV, TRPVL, TRPM, TRPS, TRPN, and TRPA. Group 2 consists of TRPP and TRPML. Other less-well categorized TRP channels exist, including yeast channels and a number of Group 1 and Group 2 channels present in non-animals. Many of these channels mediate a variety of sensations such as pain, temperature, different kinds of taste, pressure, and vision. In the body, some TRP channels are thought to behave like microscopic thermometers and used in animals to sense hot or cold. Some TRP channels are activated by molecules found in spices like garlic (allicin), chili pepper (capsaicin), wasabi ; others are activated by menthol, camphor, peppermint, and cooling agents; yet others are activated by molecules found in cannabis or stevia. Some act as sensors of osmotic pressure, volume, stretch, and vibration. Most of the channels are activated or inhibited by signaling lipids and contribute to a family of lipid-gated ion channels.

<span class="mw-page-title-main">TRPV1</span> Human protein for regulating body temperature

The transient receptor potential cation channel subfamily V member 1 (TRPV1), also known as the capsaicin receptor and the vanilloid receptor 1, is a protein that, in humans, is encoded by the TRPV1 gene. It was the first isolated member of the transient receptor potential vanilloid receptor proteins that in turn are a sub-family of the transient receptor potential protein group. This protein is a member of the TRPV group of transient receptor potential family of ion channels. Fatty acid metabolites with affinity for this receptor are produced by cyanobacteria, which diverged from eukaryotes at least 2000 million years ago (MYA). The function of TRPV1 is detection and regulation of body temperature. In addition, TRPV1 provides a sensation of scalding heat and pain (nociception). In primary afferent sensory neurons, it cooperates with TRPA1 to mediate the detection of noxious environmental stimuli.

<span class="mw-page-title-main">TRPV</span> Subgroup of TRP cation channels named after the vanilloid receptor

TRPV is a family of transient receptor potential cation channels in animals. All TRPVs are highly calcium selective.

<span class="mw-page-title-main">Capsazepine</span> Chemical compound

Capsazepine is a synthetic antagonist of capsaicin. It is used as a biochemical tool in the study of TRPV ion channels.

<span class="mw-page-title-main">TRPA1</span> Protein and coding gene in humans

Transient receptor potential cation channel, subfamily A, member 1, also known as transient receptor potential ankyrin 1, TRPA1, or The Wasabi Receptor, is a protein that in humans is encoded by the TRPA1 gene.

<span class="mw-page-title-main">TRPM5</span> Protein-coding gene in the species Homo sapiens

Transient receptor potential cation channel subfamily M member 5 (TRPM5), also known as long transient receptor potential channel 5 is a protein that in humans is encoded by the TRPM5 gene.

<span class="mw-page-title-main">TRPV2</span> Protein-coding gene in the species Homo sapiens

Transient receptor potential cation channel subfamily V member 2 is a protein that in humans is encoded by the TRPV2 gene. TRPV2 is a nonspecific cation channel that is a part of the TRP channel family. This channel allows the cell to communicate with its extracellular environment through the transfer of ions, and responds to noxious temperatures greater than 52 °C. It has a structure similar to that of potassium channels, and has similar functions throughout multiple species; recent research has also shown multiple interactions in the human body.

<span class="mw-page-title-main">TRPV4</span> Protein-coding gene in humans

Transient receptor potential cation channel subfamily V member 4 is an ion channel protein that in humans is encoded by the TRPV4 gene.

<span class="mw-page-title-main">TRPM8</span> Protein-coding gene in humans

Transient receptor potential cation channel subfamily M (melastatin) member 8 (TRPM8), also known as the cold and menthol receptor 1 (CMR1), is a protein that in humans is encoded by the TRPM8 gene. The TRPM8 channel is the primary molecular transducer of cold somatosensation in humans. In addition, mints can desensitize a region through the activation of TRPM8 receptors.

Zucapsaicin (Civanex) is a medication used to treat osteoarthritis of the knee and other neuropathic pain. Zucapsaicin is a member of phenols and a member of methoxybenzenes. It is a modulator of transient receptor potential cation channel subfamily V member 1 (TRPV-1), also known as the vanilloid or capsaicin receptor 1 that reduces pain, and improves articular functions. It is the cis-isomer of capsaicin. Civamide, manufactured by Winston Pharmaceuticals, is produced in formulations for oral, nasal, and topical use.

<span class="mw-page-title-main">Infrared sensing in vampire bats</span>

Vampire bats have developed a specialized system using infrared-sensitive receptors on their nose-leaf to prey on homeothermic (warm-blooded) vertebrates. Trigeminal nerve fibers that innervate these IR-sensitive receptors may be involved in detection of infrared thermal radiation emitted by their prey. This may aid bats in locating blood-rich areas on their prey. In addition, neuroanatomical and molecular research has suggested possible similarities of IR-sensing mechanisms between vampire bats and IR-sensitive snakes. Infrared sensing in vampire bats has not yet been hypothesized to be image forming, as it was for IR-sensitive snakes. While the literature on IR-sensing in vampire bats is thin, progress continues to be made in this field to identify how vampire bats can sense and use infrared thermal radiation.

<span class="mw-page-title-main">Vanilloid</span> Chemical compounds containing a vanillyl group

The vanilloids are compounds which possess a vanillyl group. They include vanillyl alcohol, vanillin, vanillic acid, acetovanillon, vanillylmandelic acid, homovanillic acid, capsaicin, etc. Isomers are the isovanilloids.

<span class="mw-page-title-main">Oh Uhtaek</span> South Korean physiologist (born 1955)

Oh Uhtaek or Oh Woo-Taek is a Korean physiologist. He is also a professor at College of Pharmacy, Seoul National University. His research is largely known for Cardiac Pain and other Visceral Pain Mechanism and as well as cloning.

<span class="mw-page-title-main">Department of Neurobiology, Harvard Medical School</span> Academic Department at Harvard University Medical School, USA

The Department of Neurobiology at Harvard Medical School is located in the Longwood Medical Area of Boston, MA. The Department is part of the Basic Research Program at Harvard Medical School, with research pertaining to development of the nervous system, sensory neuroscience, neurophysiology, and behavior. The Department was founded by Stephen W. Kuffler in 1966, the first department dedicated to Neurobiology in the world. The mission of the Department is “to understand the workings of the brain through basic research and to use that knowledge to work toward preventive and therapeutic methods that alleviate neurological diseases”.

RhTx is a small peptide toxin from Scolopendra subspinipes mutilans, also called the Chinese red-headed centipede. RhTx binds to the outer pore region of the temperature regulated TRPV1 ion channel, preferably in activated state, causing a downwards shift in the activation threshold temperature, which leads to the immediate onset of heat pain.

Diana M. Bautista is an American neuroscientist known for her work on the molecular mechanisms underlying itch, touch and pain. She is a full professor of cell and developmental biology in the Department of Molecular and Cell Biology and is affiliated with the Helen Wills Neuroscience Institute at the University of California, Berkeley.

<span class="mw-page-title-main">Ardem Patapoutian</span> Molecular biologist, neuroscientist, and Nobel laureate 2021

Ardem Patapoutian is a Lebanese-American molecular biologist, neuroscientist, and Nobel Prize laureate of Armenian descent. He is known for his work in characterizing the PIEZO1, PIEZO2, and TRPM8 receptors that detect pressure, menthol, and temperature. Patapoutian is a neuroscience professor and Howard Hughes Medical Institute investigator at Scripps Research in La Jolla, California. In 2021, he won the Nobel Prize in Physiology or Medicine jointly with David Julius.

The 2021 Nobel Prize in Physiology or Medicine was jointly awarded to the American physiologist David Julius and Armenian-American neuroscientist Ardem Patapoutian "for the discovery of receptors for temperature and touch." During the award ceremony on December 10, 2021, Nobel Assembly at Karolinska Institutet member Patrik Ernfors expressed:

"The 2021 Nobel Prize laureates have explained fundamental mechanisms underpinning how we sense the world within and around us. Our temperature and touch sensors are used all the time in every day of our lives. They continuously keep us updated about our environment, and without them even the simplest of our daily tasks would be impossible to perform."

References

  1. ↑ "Julius Lab at UCSF Mission Bay | David Julius Lab". Archived from the original on May 23, 2013. Retrieved November 30, 2013.
  2. ↑ "Julius Named to Receive the Shaw Prize". ucsf.edu. Archived from the original on April 29, 2019. Retrieved December 5, 2016.
  3. ↑ "David Julius, PhD 49th Faculty Research Lecture Award". senate.ucsf.edu. Archived from the original on August 1, 2020. Retrieved December 5, 2016.
  4. 1 2 "2020 Kavli Prize in Neuroscience". www.kavliprize.org. Archived from the original on June 15, 2020. Retrieved May 27, 2020.
  5. ↑ "The Nobel Prize in Physiology or Medicine 2021". NobelPrize.org. Archived from the original on October 4, 2021. Retrieved October 4, 2021.
  6. ↑ Hanau, Shira (October 4, 2021). "Scientist David Julius, whose grandparents fled antisemitism in Czarist Russia, wins Nobel Prize in medicine". Jewish Telegraphic Agency. Retrieved October 4, 2021.
  7. 1 2 Mueller, Benjamin; Santora, Marc; Engelbrecht, Cora (October 4, 2021). "Nobel Prize Awarded for Research About Temperature and Touch". New York Times. Retrieved October 5, 2021.
  8. ↑ Julius, David Jay (1984). Protein Processing and Secretion in Yeast: Biosynthesis of Alpha-Factor Mating Pheromone (Ph.D. thesis). University of California, Berkeley. OCLC   21756165. ProQuest   303332941.
  9. ↑ Julius, D.; MacDermott, A. B.; Axel, R.; Jessell, T. M. (July 29, 1988). "Molecular characterization of a functional cDNA encoding the serotonin 1c receptor". Science. 241 (4865): 558–564. Bibcode:1988Sci...241..558J. doi:10.1126/science.3399891. ISSN   0036-8075. PMID   3399891.
  10. ↑ "David Julius '77 shares the Nobel Prize in physiology or medicine". MIT News | Massachusetts Institute of Technology. Retrieved October 7, 2021.
  11. ↑ "The Nobel Prize in Physiology or Medicine 2021". NobelPrize.org. Retrieved October 7, 2021.
  12. 1 2 Caterina, M. J.; Schumacher, M. A.; Tominaga, M.; Rosen, T. A.; Levine, J. D.; Julius, D. (October 23, 1997). "The capsaicin receptor: a heat-activated ion channel in the pain pathway". Nature. 389 (6653): 816–824. Bibcode:1997Natur.389..816C. doi: 10.1038/39807 . ISSN   0028-0836. PMID   9349813. S2CID   7970319.
  13. ↑ Tominaga, M.; Caterina, M. J.; Malmberg, A. B.; Rosen, T. A.; Gilbert, H.; Skinner, K.; Raumann, B. E.; Basbaum, A. I.; Julius, D. (September 1998). "The cloned capsaicin receptor integrates multiple pain-producing stimuli". Neuron. 21 (3): 531–543. doi: 10.1016/S0896-6273(00)80564-4 . ISSN   0896-6273. PMID   9768840. S2CID   2054891.
  14. ↑ Caterina, M. J.; Leffler, A.; Malmberg, A. B.; Martin, W. J.; Trafton, J.; Petersen-Zeitz, K. R.; Koltzenburg, M.; Basbaum, A. I.; Julius, D. (April 14, 2000). "Impaired nociception and pain sensation in mice lacking the capsaicin receptor". Science. 288 (5464): 306–313. Bibcode:2000Sci...288..306C. doi:10.1126/science.288.5464.306. ISSN   0036-8075. PMID   10764638.
  15. ↑ McKemy, David D.; Neuhausser, Werner M.; Julius, David (March 7, 2002). "Identification of a cold receptor reveals a general role for TRP channels in thermosensation". Nature. 416 (6876): 52–58. Bibcode:2002Natur.416...52M. doi:10.1038/nature719. ISSN   0028-0836. PMID   11882888. S2CID   4340358.
  16. ↑ Bautista, Diana M.; Siemens, Jan; Glazer, Joshua M.; Tsuruda, Pamela R.; Basbaum, Allan I.; Stucky, Cheryl L.; Jordt, Sven-Eric; Julius, David (July 12, 2007). "The menthol receptor TRPM8 is the principal detector of environmental cold". Nature. 448 (7150): 204–208. Bibcode:2007Natur.448..204B. doi:10.1038/nature05910. ISSN   1476-4687. PMID   17538622. S2CID   4427901.
  17. ↑ Jordt, Sven-Eric; Bautista, Diana M.; Chuang, Huai-Hu; McKemy, David D.; Zygmunt, Peter M.; Högestätt, Edward D.; Meng, Ian D.; Julius, David (January 15, 2004). "Mustard oils and cannabinoids excite sensory nerve fibres through the TRP channel ANKTM1". Nature. 427 (6971): 260–265. Bibcode:2004Natur.427..260J. doi:10.1038/nature02282. ISSN   1476-4687. PMID   14712238. S2CID   4354737.
  18. ↑ Bohlen, Christopher J.; Chesler, Alexander T.; Sharif-Naeini, Reza; Medzihradszky, Katalin F.; Zhou, Sharleen; King, David; Sánchez, Elda E.; Burlingame, Alma L.; Basbaum, Allan I. (November 16, 2011). "A heteromeric Texas coral snake toxin targets acid-sensing ion channels to produce pain". Nature. 479 (7373): 410–414. Bibcode:2011Natur.479..410B. doi:10.1038/nature10607. ISSN   1476-4687. PMC   3226747 . PMID   22094702.
  19. ↑ Gracheva, Elena O.; Ingolia, Nicholas T.; Kelly, Yvonne M.; Cordero-Morales, Julio F.; Hollopeter, Gunther; Chesler, Alexander T.; Sánchez, Elda E.; Perez, John C.; Weissman, Jonathan S. (April 15, 2010). "Molecular basis of infrared detection by snakes". Nature. 464 (7291): 1006–1011. Bibcode:2010Natur.464.1006G. doi:10.1038/nature08943. ISSN   1476-4687. PMC   2855400 . PMID   20228791.
  20. ↑ Liao, Maofu; Cao, Erhu; Julius, David; Cheng, Yifan (December 5, 2013). "Structure of the TRPV1 ion channel determined by electron cryo-microscopy". Nature. 504 (7478): 107–112. Bibcode:2013Natur.504..107L. doi:10.1038/nature12822. ISSN   1476-4687. PMC   4078027 . PMID   24305160.
  21. ↑ Cao, Erhu; Liao, Maofu; Cheng, Yifan; Julius, David (December 5, 2013). "TRPV1 structures in distinct conformations reveal activation mechanisms". Nature. 504 (7478): 113–118. Bibcode:2013Natur.504..113C. doi:10.1038/nature12823. ISSN   1476-4687. PMC   4023639 . PMID   24305161.
  22. ↑ Lustig, K D; Shiau, A K; Brake, A J; Julius, D (June 1, 1993). "Expression cloning of an ATP receptor from mouse neuroblastoma cells". Proceedings of the National Academy of Sciences. 90 (11): 5113–5117. doi:10.1073/pnas.90.11.5113. ISSN   0027-8424. PMC   46665 . PMID   7685114.
  23. ↑ Brake, Anthony J.; Wagenbach, Michael J.; Julius, David (October 6, 1994). "New structural motif for ligand-gated ion channels defined by an ionotropic ATP receptor". Nature. 371 (6497): 519–523. doi:10.1038/371519a0. ISSN   0028-0836.
  24. ↑ Hollopeter, Gunther; Jantzen, Hans-Michael; Vincent, Diana; Li, Georgia; England, Laura; Ramakrishnan, Vanitha; Yang, Ruey-Bing; Nurden, Paquita; Nurden, Alan; Julius, David; Conley, Pamela B. (January 11, 2001). "Identification of the platelet ADP receptor targeted by antithrombotic drugs". Nature. 409 (6817): 202–207. doi:10.1038/35051599. ISSN   0028-0836.
  25. ↑ Maricq, Andres V.; Peterson, Andrew S.; Brake, Anthony J.; Myers, Richard M.; Julius, David (October 18, 1991). "Primary Structure And Functional Expression of the 5HT 3 Receptor, A Serotonin-gated Ion Channel". Science. 254 (5030): 432–437. doi:10.1126/science.1718042. ISSN   0036-8075.
  26. ↑ Julius, David (2007). "David Julius for the ARP Editorial Committee". Annual Review of Physiology. 69. doi:10.1146/annurev.ph.69.013107.100001.
  27. ↑ "Editor of the Annual Review of Physiology - Volume 82, 2020". Annual Reviews. Retrieved July 26, 2021.
  28. ↑ "International Prize for Translational Neuroscience". www.mpg.de. Retrieved September 29, 2024.
  29. ↑ "Julius Axelrod Prize". www.sfn.org. Retrieved September 29, 2024.
  30. ↑ "David Julius – Gairdner Foundation". Gairdner Foundation. Archived from the original on October 22, 2020. Retrieved November 1, 2018.
  31. ↑ "The 2017 HFSP Nakasone Award goes to David Julius | Human Frontier Science Program". www.hfsp.org. Archived from the original on November 9, 2018. Retrieved November 9, 2018.
  32. ↑ "Breakthrough Prize – Winners Of The 2020 Breakthrough Prize In Life Sciences, Fundamental Physics And Mathematics Announced". breakthroughprize.org. Archived from the original on December 14, 2019. Retrieved October 4, 2021.
  33. ↑ "homepage". Premios Fronteras. Archived from the original on September 21, 2021. Retrieved October 4, 2021.
  34. ↑ "The Nobel Prize in Physiology or Medicine 2021". NobelPrize.org. Archived from the original on October 4, 2021. Retrieved October 4, 2021.
  35. ↑ "UCSF Medal | Office of the Chancellor". chancellor.ucsf.edu. Retrieved September 29, 2024.
  36. ↑ "John J. Bonica Award". ASRA Pain Medicine. Retrieved September 29, 2024.
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