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Karl Deisseroth

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Karl Deisseroth
Deisseroth in 2022
Born (1971-11-18) November 18, 1971 (age 53)
Boston, Massachusetts, US
Alma materHarvard University
Stanford University
Known forOptogenetics and Hydrogel-Tissue Chemistry (including CLARITY and STARmap)
SpouseMichelle Monje
AwardsNAMedi (2010)
NAS (2012)
NAE (2019)
W. Alden Spencer Award (2011)
Keio Medical Science Prize (2014)
Albany Medical Center Prize (2015)
BBVA Foundation Frontiers of Knowledge Award (2015)
Breakthrough Prize in Life Sciences (2016)
Kyoto Prize (2018)
Heineken Prize (2020)
Albert Lasker Award for Basic Medical Research (2021)
Louisa Gross Horwitz Prize (2022)
Japan Prize (2023)
Scientific career
Fields
InstitutionsStanford University
Academic advisorsRichard Tsien, Robert Malenka
Doctoral studentsFeng Zhang, Viviana Gradinaru
Websiteweb.stanford.edu/group/dlab/index.html

Karl Alexander Deisseroth (born November 18, 1971) is an American scientist. He is the D.H. Chen Foundation Professor of Bioengineering and of psychiatry and behavioral sciences at Stanford University.

He is known for creating and developing the technologies of hydrogel-tissue chemistry (e.g., CLARITY, STARmap) and optogenetics, and for applying integrated optical and genetic strategies to study normal neural circuit function, as well as dysfunction in neurological and psychiatric disease.

In 2019, Deisseroth was elected as a member of the US National Academy of Engineering for molecular and optical tools for his discovery and control of neuronal signals behind animal behavior in health and disease. He is also a member of the US National Academy of Sciences and the US National Academy of Medicine.

Education

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Deisseroth earned his BA in biochemical sciences from Harvard University, and his MD and PhD in neuroscience from Stanford University in 1998. He completed his medical internship and psychiatry residency at Stanford University School of Medicine.

Career

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Deisseroth has led his laboratory at Stanford University since 2004.[citation needed] He serves as an attending physician at Stanford Hospital and Clinics and has been affiliated with the Howard Hughes Medical Institute (HHMI) since 2009.[1][2] Between 2014 and 2019, he was a foreign adjunct professor at Sweden's Karolinska Medical Institute.[citation needed]

In 2021, he authored a book titled Projections: A Story of Human Emotions, published by Random House, where he explores the origins of human emotions through personal encounters with patients.[3]

Research

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Light-gated ion channels, optogenetics, and neural circuits of behavior

Deisseroth named this field "optogenetics" in 2006 and followed up with optogenetic technology development work leading to many applications, including psychiatry and neurology. In 2010, the journal Nature Methods named optogenetics "Method of the Year".[4]

For developing optogenetics, Deisseroth received in 2010 the Nakasone Award; in 2013 the Lounsbery Award and the Dickson Prize in Science; in 2014 the Keio Medical Science Prize; and in 2015 the Albany Prize, Lurie Prize, Dickson Prize in Medicine, and Breakthrough Prize in Life Sciences.[5] He also received the 2015 BBVA Foundation Frontiers of Knowledge Award in Biomedicine, jointly with Edward Boyden and Gero Miesenböck. In 2016, Deisseroth received the Massry Prize along with Peter Hegemann and Miesenböck for "optogenetics, a technology that utilizes light to control cells in living tissues".[6] In 2016, the Harvey Prize from the Technion in Israel was awarded to Deisseroth and Hegemann "for their discovery of opsin molecules, involved in sensing light in microorganisms, and their pioneering work in using these opsins to develop optogenetics".[7] Deisseroth was then awarded Japan's highest private prize, the Kyoto Prize, in 2018, for "his discovery of optogenetics and the development of causal systems neuroscience", becoming the youngest recipient of the award to date.[8][9] In 2019, Deisseroth, Hegemann, Boyden, and Miesenböck won the Warren Alpert Foundation Prize.[10] Finally in 2020, Deisseroth received the Heineken Prize from the Royal Netherlands Academy of Arts and Sciences, "for developing optogenetics — a method to influence the activity of nerve cells with light".[11]

Deisseroth is also known for achieving insight into the light-gated ion channel pore of channelrhodopsin itself, through his teams' initial high-resolution crystal structures of cation and anion-conducting channelrhodopsins[12][13][14] and through a body of structure/function work discovering mechanisms of channelrhodopsin kinetics, ion selectivity, and color selectivity, together with his frequent collaborator Peter Hegemann.[15] Two major prizes paid particular attention to Deisseroth's work on elucidation of the structure and function of light-gated ion channels—the 2016 Harvey Prize to Deisseroth and Hegemann for the "discovery of opsin molecules, involved in sensing light in microorganisms, and for the pioneering work in utilizing these opsins to develop optogenetics",[7] and the 2018 Gairdner Award, which noted "his group discovered the fundamental principles of the unique channelrhodopsin proteins in molecular detail by a wide range of genomic, biophysical, electrophysiological and structural techniques with many mutants in close collaboration with Peter Hegemann").[16]

Although the first peer-reviewed paper[17] demonstrating activation of neurons with a channelrhodopsin was from his lab in mid-2005, Deisseroth has emphasized that many "pioneering laboratories around the world"[18] were also working on the idea and published their papers within the following year; he cites Stefan Herlitze[19] and Alexander Gottschalk/Georg Nagel,[20] who published their papers in late 2005, and Hiromu Yawo[21] and Zhuo-Hua Pan,[22] who published their initial papers in 2006 (Pan's early observation of optical activation of retinal neurons expressing channelrhodopsin would have occurred in August 2004, according to Pan,[23] about a month after Deisseroth's initial observation). Deisseroth has published the notebook pages from early July 2004 of his initial experiment showing light activation of neurons expressing a channelrhodopsin.[24] Deisseroth also pointed out[24] that an even earlier experiment had occurred and was published by Heberle and Büldt in 1994, in which functional heterologous expression of a bacteriorhodopsin for light-activated ion flow had been published in a non-neural system (yeast).[25] Optogenetics with microbial opsins as a general technology for neuroscience was enabled only by the full development of versatile strategies for targeting opsins and light to specific cells in behaving animals by taking advantage of Cre-lox neurogenetics developed by Joe Tsien in the 1990s.[24][26][27]

Other awards:

  • Deisseroth's 2018 Kyoto Prize cited his "causal systems neuroscience".[28]
  • The 2013 Pasarow Prize[29] was awarded to Deisseroth for "neuropsychiatry research".[30]
  • The 2013 Premio Citta di Firenze was given to Deisseroth for "innovative technologies to probe the structure and dynamics of circuits related to schizophrenia, autism, narcolepsy, Parkinson's disease, depression, anxiety and addiction".[31]
  • The Redelsheimer Award from the Society for Biological Psychiatry was awarded to Deisseroth for "furthering the field's understanding of the neuroscience underlying behavior".[32]
  • Deisseroth's 2017 Fresenius Prize[33] cited "his discoveries in optogenetics and hydrogel-tissue chemistry, as well as his research into the neural circuit basis of depression".[34]

Chemical assembly of functional materials in tissue

Deisseroth is known also for a separate class of technological innovation. His group has developed methods for chemical assembly of functional materials within biological tissue. This approach has a range of applications, including probing the molecular composition and wiring of cells within intact brains.

In 2013, Deisseroth was senior author of a paper describing the initial form of this method, called CLARITY (with a team including first author postdoctoral fellow in his lab Kwanghun Chung,[35] and neuroscientist Viviana Gradinaru).[36] This method makes biological tissues, such as mammalian brains, translucent and accessible to molecular probes.[37] CLARITY[38] has been widely used,[39] and many variants on the basic HTC backbone have been developed in other labs as well since 2013 (reviewed in[40]).

A key feature of HTC is that the hydrogel-tissue hybrid "becomes the substrate for future chemical and optical interrogation that can be probed and manipulated in new ways".[40] For example, HTC variants now enable improved anchoring and amplification of RNA, reversible size changes (contraction or expansion), and in situ sequencing (reviewed in[40]). In particular, STARmap is an HTC variant that allows three-dimensional cellular-resolution transcriptomic readouts within intact tissue.[41][42][43])

Several major prizes have cited Deisseroth's development of HTC, including:

  • The 2017 Fresenius Prize "for his discoveries in optogenetics and hydrogel-tissue chemistry, as well as his research into the neural circuit basis of depression".[44][33][45]
  • The 2015 Lurie Prize in Biomedical Sciences "for leading the development of optogenetics, a technology for controlling cells with light to determine function, as well as for CLARITY, a method for transforming intact organs into transparent polymer gels to allow visualization of biological structures with high resolution and detail".[46]
  • The 2013 Premio Citta di Firenze[31]
  • The Redelsheimer Award for "optogenetics, CLARITY, and other novel and powerful neural circuit approaches in furthering the field's understanding of the neuroscience underlying behavior".[47]
  • The 2015 Dickson Prize in Medicine[48]
  • The 2020 Heineken Prize for Medicine, for "developing optogenetics — a method to influence the activity of nerve cells with light — as well as for developing hydrogel-tissue chemistry, which enables researchers to make biological tissue accessible to light and molecular probes."[49]

Honors and awards

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Personal life

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Deisseroth is married to neuroscientist Michelle Monje, with whom he has four children.[citation needed]

References

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  1. ^ "Karl Deisseroth, MD, PhD". HHMI.org. Retrieved March 1, 2016.
  2. ^ Smith, Kerri (May 29, 2013). "Neuroscience: Method man". Nature News. Retrieved February 27, 2014.
  3. ^ "Projections by Karl Deisseroth: 9781984853691 | PenguinRandomHouse.com: Books". PenguinRandomhouse.com. Retrieved January 18, 2022.
  4. ^ "Method of the Year 2010". Nature Methods. 8 (1): 1. December 20, 2010. doi:10.1038/nmeth.f.321.
  5. ^ a b "Breakthrough Prize". Breakthrough Prize. Retrieved March 1, 2016.
  6. ^ "MASSRY PRIZE 2016" (PDF). keck.usc.edu. Retrieved September 15, 2020.
  7. ^ a b "Harvey Prize – Prize Winners". Retrieved September 15, 2020.
  8. ^ "2018 Kyoto Prize Laureates received their Awards on November 10 | Kyoto Prize USA". Retrieved June 12, 2019.
  9. ^ Scovie, Jay (2018). "Stanford Neuroscientist Karl Deisseroth Receives Japan's Kyoto Prize in Advanced Technology". Business Wire. Retrieved June 13, 2019.
  10. ^ a b "2019 Warren Alpert Prize Recipients Announced | Warren Alpert Foundation Prize". warrenalpert.org. Retrieved July 16, 2019.
  11. ^ "Karl Deisseroth wins 2020 Heineken Prize for Medicine". News Center. June 3, 2020. Retrieved July 23, 2022.
  12. ^ Kim YS (September 2018). "Crystal Structure of the Natural Anion-Conducting Channelrhodopsin GtACR1". Nature. 561 (7723): 343–348. Bibcode:2018Natur.561..343K. doi:10.1038/s41586-018-0511-6. PMC 6340299. PMID 30158696.
  13. ^ Kato HE (January 22, 2012). "Crystal Structure of the Channelrhodopsin Light-Gated Cation Channel". Nature. 365 (6453): 369–74. Bibcode:2012Natur.482..369K. doi:10.1038/nature10870. PMC 4160518. PMID 22266941.
  14. ^ Kato HE (September 2018). "Structural mechanisms of selectivity and gating in anion channelrhodopsins". Nature. 561 (7723): 349–354. Bibcode:2018Natur.561..349K. doi:10.1038/s41586-018-0504-5. PMC 6317992. PMID 30158697.
  15. ^ Deisseroth K; Hegemann P (September 15, 2017). "The Form and Function of Channelrhodopsin". Science. 357 (6356): eaan5544. doi:10.1126/science.aan5544. PMC 5723383. PMID 28912215.
  16. ^ "Karl Deisseroth – 2018 Gairdner Awards Laureate". Retrieved December 13, 2021.
  17. ^ Boyden ES; Zhang F; Bamberg E; Nagel G; Deisseroth K (September 2005). "Millisecond-timescale, genetically targeted optical control of neural activity". Nature Neuroscience. 8 (9): 1263–8. doi:10.1038/nn1525. PMID 16116447. S2CID 6809511.
  18. ^ Deisseroth K (September 2015). "Optogenetics: 10 years of microbial opsins in neuroscience". Nature Neuroscience. 18 (9): 1213–1225. doi:10.1038/nn.4091. PMC 4790845. PMID 26308982.
  19. ^ Li X; Gutierrez DV; Hanson MG; Han J; Mark MD; Chiel H; Hegemann P; Landmesser LT; Herlitze S (December 6, 2005). "Fast Noninvasive Activation and Inhibition of Neural and Network Activity by Vertebrate Rhodopsin and Green Algae Channelrhodopsin". Proc Natl Acad Sci USA. 102 (49): 17816–21. Bibcode:2005PNAS..10217816L. doi:10.1073/pnas.0509030102. PMC 1292990. PMID 16306259.
  20. ^ Nagel G; Brauner M; Liewald J; Adeishvili N; Bamberg E; Gottschalk A (December 2005). "Light activation of channelrhodopsin-2 in excitable cells of Caenorhabditis elegans triggers rapid behavioral responses". Current Biology. 15 (24): 2279–2284. doi:10.1016/j.cub.2005.11.032. PMID 16360690. S2CID 7036529.
  21. ^ Ishizuka T; Kakuda M; Araki R; Yawo H (2006). "Kinetic Evaluation of Photosensitivity in Genetically Engineered Neurons Expressing Green Algae Light-Gated Channels". Neuroscience Research. 54 (2): 85–94. doi:10.1016/j.neures.2005.10.009. PMID 16298005. S2CID 17576414.
  22. ^ Bi A; Cui J; Ma Y; Olshevskaya E; Pu M; Dizhoor A; Pan Z (2006). "Ectopic expression of a microbial-type rhodopsin restores visual responses in mice with photoreceptor degeneration". Neuron. 50 (1): 23–33. doi:10.1016/j.neuron.2006.02.026. PMC 1459045. PMID 16600853.
  23. ^ "He may be the rightful inventor of neuroscience's biggest breakthrough in decades. But you've never heard of him". STAT. September 1, 2016. Retrieved February 9, 2020.
  24. ^ a b c Deisseroth K. (September 2015). "Optogenetics: 10 years of microbial opsins in neuroscience". Nature Neuroscience. 18 (9): 1213–25. doi:10.1038/nn.4091. PMC 4790845. PMID 26308982.
  25. ^ Hoffman A; Hildebrandt V; Heberle J; Buldt G (1994). "Photoactive mitochondria: in vivo transfer of a light-driven proton pump into the inner mitochondrial membrane of Schizosaccharomyces pombe". Proc. Natl. Acad. Sci. USA. 91 (20): 9367–9371. Bibcode:1994PNAS...91.9367H. doi:10.1073/pnas.91.20.9367. PMC 44813. PMID 7937771.
  26. ^ Joe Z. Tsien; et al. (1996). "Subregion- and cell type-restricted gene knockout in mouse brain". Cell. 87 (7): 1317–1326. doi:10.1016/S0092-8674(00)81826-7. PMID 8980237. S2CID 863399.
  27. ^ Tsien JZ. (2016). Cre-lox neurogenetics: 20 years of versatile applications in brain research and counting...Front. Genet. | doi:10.3389/fgene.2016.00019 http://journal.frontiersin.org/article/10.3389/fgene.2016.00019/abstract
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  29. ^ "Three researchers earn Pasarow Awards". News Center.
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  31. ^ a b "Premio Città di Firenze".
  32. ^ "Karl Deisseroth receives Inaugural SOBP Distinguished Redelsheimer Award".
  33. ^ a b https://web.stanford.edu/group/dlab/media/documents/fresenius.pdf doi:10.15252/embr.201744400
  34. ^ "Else Kröner Fresenius Prize for Medical Research 2017". ekfs.de. Retrieved September 15, 2020.
  35. ^ Deisseroth KA, Chung K. 2015. Methods and compositions for preparing biological specimens for microscopic analysis. www.google.com/patents/US20150144490. Filing date: March 13, 2013. US Patent Appl. No. US20150144490
  36. ^ Deisseroth KA, Gradinaru V. 2014. Functional targeted brain endoskeletonization. www.google.com/patents/US20140030192. Filing date: January 26, 2012. US Patent Appl. No. US20140030192.
  37. ^ "Brains as Clear as Jell-O for Scientists to Explore", April 10, 2013 The New York Times
  38. ^ "CLARITY Wiki". wiki.claritytechniques.org.
  39. ^ "Journal Articles – CLARITY Wiki". wiki.claritytechniques.org.
  40. ^ a b c Viviana Gradinaru; Jennifer Treweek; Kristin Overton; Karl Deisseroth (2018). "Hydrogel-tissue chemistry: principles and applications". Annual Review of Biophysics. 47: 355–376. doi:10.1146/annurev-biophys-070317-032905. PMC 6359929. PMID 29792820.
  41. ^ Wang, X (June 21, 2018). "Three-dimensional intact-tissue sequencing of single-cell transcriptional states". Science. 361 (6400). doi:10.1126/science.361.6400.375-I. PMC 6339868. PMID 29930089.
  42. ^ Thomas Knopfel (July 27, 2018). "Neurotechnology to address big questions". Science. 361 (6400): 328–329. Bibcode:2018Sci...361..328K. doi:10.1126/science.aau4705. hdl:10044/1/71425. PMID 30049862. S2CID 50787948.
  43. ^ "STARmap Resources". STARmap Resources.
  44. ^ "Else Kröner Fresenius Prize for Medical Research 2017 | Else Kröner-Fresenius-Stiftung". www.ekfs.de.
  45. ^ Deisseroth K (2017). "Optical and chemical discoveries recognized for impact on biology and psychiatry". EMBO Reports. 18 (6): 859–60. doi:10.15252/embr.201744405. PMC 5452044. PMID 28566521.
  46. ^ "FNIH Awards Lurie Prize to Karl Deisseroth | The Foundation for the National Institutes of Health". fnih.org. April 27, 2023.
  47. ^ "Karl Deisseroth receives Inaugural SOBP Distinguished Redelsheimer Award".
  48. ^ "2015 Dickson Prize Winner".
  49. ^ a b "Dr A.H. Heineken Prize for Medicine 2020 awarded to Karl Deisseroth — KNAW". knaw.nl.
  50. ^ "White House Announces 2005 Awards for Early Career Scientists and Engineers" (PDF). Office of Science and Technology Policy, Executive Office of the President. July 26, 2006. Retrieved November 12, 2018 – via Center for Space Research, University of Texas at Austin.
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  52. ^ "Koetser Prize Former-Awardees".
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  54. ^ "2012 Zuelch Prize".
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  66. ^ "2015 BBVA Award". YouTube. June 24, 2016.
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  68. ^ "2017 Redelsheimer Award".
  69. ^ "2017 Fresenius Prize". "Fresenius" (PDF).
  70. ^ "2017 Harvey Prize" (PDF).
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  72. ^ "2018 Eisenberg".
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  75. ^ Hofschneider, Mark. "Light-sensitive microbial proteins and optogenetics". Lasker Foundation. Retrieved December 13, 2021.
  76. ^ Louisa Gross Horwitz Prize 2022
  77. ^ Japan Prize 2023
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