Gary Siuzdak Explained

Gary Siuzdak
Birth Date:December 29, 1961
Fields:Analytical Chemistry, Metabolomics

Gary Siuzdak is an American chemist best known for his work in the field of metabolomics,[1] [2] activity metabolomics[3] [4] [5] [6] (a termed coined in 2019[7]), and mass spectrometry.[8] His lab discovered indole-3-propionic acid as a gut bacteria derived metabolite in 2009. He is currently the Professor and Director of The Center for Metabolomics and Mass Spectrometry at Scripps Research in La Jolla, California.[9] Siuzdak has also made contributions to virus analysis, viral structural dynamics,[10] [11] [12] as well as developing mass spectrometry imaging technology using nanostructured surfaces. The Siuzdak lab is also responsible for creating the research tools eXtensible Computational Mass Spectrometry (XCMS),[13] METLIN,[14] METLIN Neutral Loss[15] and Q-MRM.[16] [17] As of January 2021,[18] the XCMS/METLIN platform has over 50,000 registered users.

Siuzdak studied chemistry (B.S.) and applied mathematics (B.A.) at Rhode Island College. He then went to Dartmouth College for his graduate work where he built his first mass spectrometer[19] to perform multi-photon ionization mass spectrometry experiments and occasionally competed in powerlifting.[20] At Dartmouth he received his Ph.D. in Physical Chemistry (March 29, 1990) and on April 1, 1990, started at Scripps Research. In 2017 Siuzdak received an honorary doctorate (with Emmanuelle Charpentier) from Umeå University[21] for his work in metabolomics. Siuzdak has hundreds of papers and has authored two books: Mass Spectrometry for Biotechnology (1996) and The Expanding Role of Mass Spectrometry in Biotechnology (2003) as well as The Expanding Role of Mass Spectrometry in Biotechnology 2nd Ed. (2006).[22]

Notable research

From 1994 to the present the Siuzdak lab has been working on activity metabolomics.[23] [24] [25] [26] using liquid chromatography mass spectrometry-based metabolomics to identify metabolites that alter phenotype. His initial efforts with Richard Lerner, used liquid chromatography mass spectrometry to perform metabolomic experiments on the cerebral spinal fluid of sleep deprived animals. cis-9,10-octadecenoamide, a novel lipid hormone (also known as oleamide), was observed and shown to have sleep inducing properties. This work is one of the earliest such experiments combining liquid chromatography mass spectrometry and metabolomics to identify active metabolites.[27] Another notable activity metabolomics effort with Oscar Yanes (Spain) identified neuroprotectin D1 as a metabolite that promotes stem cell differentiation.

In 1996 whole virus analysis was performed with an electrospray ionization mass spectrometer where the virus was collected and successfully tested for viability.[28] Later, he and his collaborators provided the first example of a whole intact virus (tobacco mosaic virus) being mass measured using a charge detection mass spectrometer, an instrument designed by Henry Benner and Stephen Fuerstenau at Lawrence Berkeley National Labs.[29]

In 1999, the Siuzdak lab described the use of nanostructures to enhance desorption/ionization on porous silicon of small molecules (DIOS),[30] this is also known as the first surface-based example of surface-assisted laser desorption/ionization mass spectrometry (SALDI-MS). This technology went on to be expanded using fluorinated initiator molecules used within the porous silicon and was described as Nanostructure Initiator Mass Spectrometry (NIMS),[31] it is also known as Nanostructure Imaging Mass Spectrometry (NIMS) because of its expanded application to imaging.[32]

In 2005, the Siuzdak lab was engaged in identifying dysregulated metabolic peaks from liquid chromatography mass spectrometry data sets, to address the issue retention time alignment they developed the first algorithm that allowed for the nonlinear alignment of metabolomics data called XCMS.[33]

From the early 2000s[34] [35] to the present, the Siuzdak lab created and has been expanding the tandem mass spectrometry database known as METLIN. METLIN is made up solely of experimental data generated from high resolution tandem mass spectrometry instrumentation, all of the data is derived from molecular standards. METLIN (as of August 2022) has over 870,000 molecular standards with experimental tandem mass spectrometry data.[36] METLIN is unique with respect to its size, as other databases are over an order of magnitude smaller, and it is also unique because all of METLIN's tandem mass spectrometry data has been systematically generated at multiple collision energies and in positive and negative ionization modes.

In 2020, the Siuzdak lab building off their work with Xavi Domingo[37] and METLIN, developed Enhanced In-Source Fragmentation/Annotation (EISA)[38] to facilitate the fragmentation, identification, and quantification (via Q-MRM)[16] [39] of molecules without the use of tandem mass spectrometry.

External links

Notes and References

  1. Guijas. Carlos. Montenegro-Burke. J. Rafael. Warth. Benedikt. Spilker. Mary E.. Siuzdak. Gary. April 2018. Metabolomics activity screening for identifying metabolites that modulate phenotype. Nature Biotechnology. en. 36. 4. 316–320. 10.1038/nbt.4101. 29621222 . 1546-1696. 5937131.
  2. Johnson. Caroline H.. Ivanisevic. Julijana. Siuzdak. Gary. July 2016. Metabolomics: beyond biomarkers and towards mechanisms. Nature Reviews Molecular Cell Biology. en. 17. 7. 451–459. 10.1038/nrm.2016.25. 26979502 . 1471-0080. 5729912.
  3. Rinschen. Markus M.. Ivanisevic. Julijana. Giera. Martin. Siuzdak. Gary. June 2019. Identification of bioactive metabolites using activity metabolomics. Nature Reviews Molecular Cell Biology. en. 20. 6. 353–367. 10.1038/s41580-019-0108-4. 30814649 . 1471-0080. 6613555.
  4. Yanes. Oscar. Clark. Julie. Wong. Diana M.. Patti. Gary J.. Sánchez-Ruiz. Antonio. Benton. H. Paul. Trauger. Sunia A.. Desponts. Caroline. Ding. Sheng. Siuzdak. Gary. June 2010. Metabolic oxidation regulates embryonic stem cell differentiation. Nature Chemical Biology. en. 6. 6. 411–417. 10.1038/nchembio.364. 20436487 . 1552-4469. 2873061.
  5. Lerner. R. A.. Siuzdak. G.. Prospero-Garcia. O.. Henriksen. S. J.. Boger. D. L.. Cravatt. B. F.. 1994-09-27. Cerebrodiene: a brain lipid isolated from sleep-deprived cats. Proceedings of the National Academy of Sciences. en. 91. 20. 9505–9508. 44841. 10.1073/pnas.91.20.9505. 0027-8424. 7937797. 1994PNAS...91.9505L . free .
  6. Montenegro-Burke. J. Rafael. Kok. Bernard P.. Guijas. Carlos. Domingo-Almenara. Xavier. Moon. Clara. Galmozzi. Andrea. Kitamura. Seiya. Eckmann. Lars. Saez. Enrique. Siuzdak. Gary E.. Wolan. Dennis W.. 2021-09-28. Metabolomics activity screening of T cell–induced colitis reveals anti-inflammatory metabolites. Science Signaling. 14. 702. eabf6584. 10.1126/scisignal.abf6584. 34582249 . 8757460 .
  7. Rinschen. Markus M.. Ivanisevic. Julijana. Giera. Martin. Siuzdak. Gary. June 2019. Identification of bioactive metabolites using activity metabolomics. Nature Reviews Molecular Cell Biology. en. 20. 6. 353–367. 10.1038/s41580-019-0108-4. 30814649 . 6613555 . 1471-0080.
  8. Giera. Martin. Yanes. Oscar. Siuzdak. Gary. 2022-01-04. Metabolite discovery: Biochemistry's scientific driver. Cell Metabolism. en. 34. 1. 21–34. 10.1016/j.cmet.2021.11.005. 34986335 . 10131248 . 245729571 . 1550-4131. free.
  9. Web site: Faculty Page, Gary Siuzdak . scripps.edu . 22 May 2019.
  10. Bothner. Brian. Dong. X. Fan. Bibbs. Lisa. Johnson. John E.. Siuzdak. Gary. 1998-01-09. Evidence of Viral Capsid Dynamics Using Limited Proteolysis and Mass Spectrometry. Journal of Biological Chemistry. en. 273. 2. 673–676. 10.1074/jbc.273.2.673. 0021-9258. 9422714. free.
  11. Lewis. J. Kathleen. Bothner. Brian. Smith. Thomas J.. Siuzdak. Gary. 1998-06-09. Antiviral agent blocks breathing of the common cold virus. Proceedings of the National Academy of Sciences. en. 95. 12. 6774–6778. 22631 . 10.1073/pnas.95.12.6774. 0027-8424. 9618488. 1998PNAS...95.6774L . free.
  12. Bothner. Brian. Schneemann. Anette. Marshall. Dawn. Reddy. Vijay. Johnson. John E.. Siuzdak. Gary. February 1999. Crystallographically identical virus capsids display different properties in solution. Nature Structural Biology. en. 6. 2. 114–116. 10.1038/5799. 10048920 . 1756648 . 1545-9985.
  13. Smith. Colin A.. Want. Elizabeth J.. O'Maille. Grace. Abagyan. Ruben. Siuzdak. Gary. 2006-02-01. XCMS: Processing Mass Spectrometry Data for Metabolite Profiling Using Nonlinear Peak Alignment, Matching, and Identification. Analytical Chemistry. 78. 3. 779–787. 10.1021/ac051437y. 16448051 . 0003-2700.
  14. Xue. Jingchuan. Guijas. Carlos. Benton. H. Paul. Warth. Benedikt. Siuzdak. Gary. 2020-08-24. METLIN MS 2 molecular standards database: a broad chemical and biological resource. Nature Methods. 17 . 10 . en. 953–954. 10.1038/s41592-020-0942-5. 32839599 . 8802982 . 1548-7105.
  15. Aisporna. Aries. Benton. H. Paul. Galano. Jean Marie. Giera. Martin. Siuzdak. Gary. 2021-04-04. METLIN Neutral Loss Database Enhances Similarity Analysis. en. 2021.04.02.438066. 10.1101/2021.04.02.438066. 233175525 .
  16. Xue. Jingchuan. Derks. Rico J. E.. Webb. Bill. Billings. Elizabeth M.. Aisporna. Aries. Giera. Martin. Siuzdak. Gary. 2021-08-10. Single Quadrupole Multiple Fragment Ion Monitoring Quantitative Mass Spectrometry. Analytical Chemistry. 93. 31. 10879–10889. 10.1021/acs.analchem.1c01246. 34313111 . 8762722 . 1887/3243130 . 0003-2700.
  17. Xue. Jingchuan. Derks. Rico J. E.. Hoang. Linh. Giera. Martin. Siuzdak. Gary. 2021-10-11. Proteomics with Enhanced In-Source Fragmentation/Annotation: Applying XCMS-EISA Informatics and Q-MRM High-Sensitivity Quantification. Journal of the American Society for Mass Spectrometry. 32 . 11 . 2644–2654 . 10.1021/jasms.1c00188. 34633184 . 238581609 . 1044-0305. 10245389.
  18. Majumder. Erica L.-W.. Billings. Elizabeth M.. Benton. H. Paul. Martin. Richard L.. Palermo. Amelia. Guijas. Carlos. Rinschen. Markus M.. Domingo-Almenara. Xavier. Montenegro-Burke. J. Rafael. Tagtow. Bradley A.. Plumb. Robert S.. 2021-01-22. Cognitive analysis of metabolomics data for systems biology. Nature Protocols. 16 . 3 . en. 1376–1418. 10.1038/s41596-020-00455-4. 33483720 . 1774918 . 231687415 . 1750-2799. 10357461.
  19. Siuzdak. Gary.. BelBruno. Joseph J.. May 1990. Laser multiphoton dissociation/ionization of butylamines: competitive processes in radical cations. The Journal of Physical Chemistry. 94. 11. 4559–4565. 10.1021/j100374a038. 0022-3654.
  20. News: Scandura . Mike . Weightlifting the right way good for Siuzdak . The Evening Times (Pawtucket, R.I.) . 30 Dec 1987.
  21. Web site: Biochemist and metabolomics researcher take honorary roles at Umeå University. 2020-10-21. www.umu.se. en.
  22. Web site: Interview with Dr. Gary Siuzdak . MetaboNews, Issue 13 - September 2012 . 22 May 2019.
  23. Patti. Gary J.. Yanes. Oscar. Shriver. Leah P.. Courade. Jean-Phillipe. Tautenhahn. Ralf. Manchester. Marianne. Siuzdak. Gary. March 2012. Metabolomics implicates altered sphingolipids in chronic pain of neuropathic origin. Nature Chemical Biology. en. 8. 3. 232–234. 10.1038/nchembio.767. 22267119 . 1552-4469. 3567618.
  24. Wikoff. William R.. Anfora. Andrew T.. Liu. Jun. Schultz. Peter G.. Lesley. Scott A.. Peters. Eric C.. Siuzdak. Gary. 2009-03-10. Metabolomics analysis reveals large effects of gut microflora on mammalian blood metabolites. Proceedings of the National Academy of Sciences. en. 106. 10. 3698–3703. 2656143. 10.1073/pnas.0812874106. 0027-8424. 19234110. 2009PNAS..106.3698W . free.
  25. Beyer. Brittney A.. Fang. Mingliang. Sadrian. Benjamin. Montenegro-Burke. J. Rafael. Plaisted. Warren C.. Kok. Bernard P. C.. Saez. Enrique. Kondo. Toru. Siuzdak. Gary. Lairson. Luke L.. January 2018. Metabolomics-based discovery of a metabolite that enhances oligodendrocyte maturation. Nature Chemical Biology. en. 14. 1. 22–28. 10.1038/nchembio.2517. 29131145 . 1552-4469. 5928791.
  26. Guijas. Carlos. Montenegro-Burke. J. Rafael. Cintron-Colon. Rigo. Domingo-Almenara. Xavier. Sanchez-Alavez. Manuel. Aguirre. Carlos A.. Shankar. Kokila. Majumder. Erica L.-W.. Billings. Elizabeth. Conti. Bruno. Siuzdak. Gary. 2020-09-08. Metabolic adaptation to calorie restriction. Science Signaling. en. 13. 648. 10.1126/scisignal.abb2490. 7580877. 1945-0877. 32900879. free.
  27. Cravatt . BF . Prospero-Garcia . O . Siuzdak . G . Gilula . NB . Henriksen . SJ . Boger . DL . Lerner . RA . Chemical characterization of a family of brain lipids that induce sleep. . Science . 9 June 1995 . 268 . 5216 . 1506–9 . 7770779. 10.1126/science.7770779 . 1995Sci...268.1506C .
  28. Siuzdak. Gary. Bothner. Brian. Yeager. Mark. Brugidou. Christophe. Fauquet. Claude M.. Hoey. Kenway. Change. Cheng-Ming. 1996-01-01. Mass spectrometry and viral analysis. Chemistry & Biology. en. 3. 1. 45–48. 10.1016/S1074-5521(96)90083-6. 8807827 . 1074-5521. free.
  29. Fuerstenau. Stephen D.. Benner. W. Henry. Thomas. John J.. Brugidou. Christophe. Bothner. Brian. Siuzdak. Gary. 2001. Mass Spectrometry of an Intact Virus. Angewandte Chemie International Edition. 40. 3. 541–544. 10.1002/1521-3773(20010202)40:3<541::AID-ANIE541>3.0.CO;2-K. 1521-3773.
  30. Wei. Jing. Buriak. Jillian M.. Siuzdak. Gary. May 1999. Desorption–ionization mass spectrometry on porous silicon. Nature. en. 399. 6733. 243–246. 10.1038/20400. 10353246 . 1999Natur.399..243W . 4314372 . 1476-4687.
  31. Northen. Trent R.. Yanes. Oscar. Northen. Michael T.. Marrinucci. Dena. Uritboonthai. Winnie. Apon. Junefredo. Golledge. Stephen L.. Nordström. Anders. Siuzdak. Gary. October 2007. Clathrate nanostructures for mass spectrometry. Nature. en. 449. 7165. 1033–1036. 10.1038/nature06195. 17960240 . 2007Natur.449.1033N . 4404703 . 1476-4687.
  32. Book: Kurczy . ME . Northen . TR . Trauger . SA . Siuzdak . G . Nanostructure Imaging Mass Spectrometry: The Role of Fluorocarbons in Metabolite Analysis and Yoctomole Level Sensitivity . Mass Spectrometry Imaging of Small Molecules . 2015 . 1203 . 141–9 . 10.1007/978-1-4939-1357-2_14 . 25361674. 4755109 . Methods in Molecular Biology . 978-1-4939-1356-5 .
  33. Tautenhahn. Ralf. Patti. Gary J.. Rinehart. Duane. Siuzdak. Gary. 2012-06-05. XCMS Online: A Web-Based Platform to Process Untargeted Metabolomic Data. Analytical Chemistry. 84. 11. 5035–5039. 10.1021/ac300698c. 0003-2700. 3703953. 22533540.
  34. Smith. Colin A.. Maille. Grace O'. Want. Elizabeth J.. Qin. Chuan. Trauger. Sunia A.. Brandon. Theodore R.. Custodio. Darlene E.. Abagyan. Ruben. Siuzdak. Gary. December 2005. METLIN: A Metabolite Mass Spectral Database. Therapeutic Drug Monitoring. en-US. 27. 6. 747–751. 10.1097/01.ftd.0000179845.53213.39. 16404815 . 14774455 . 0163-4356.
  35. Guijas. Carlos. Montenegro-Burke. J. Rafael. Domingo-Almenara. Xavier. Palermo. Amelia. Warth. Benedikt. Hermann. Gerrit. Koellensperger. Gunda. Huan. Tao. Uritboonthai. Winnie. Aisporna. Aries E.. Wolan. Dennis W.. 2018-03-06. METLIN: A Technology Platform for Identifying Knowns and Unknowns. Analytical Chemistry. 90. 5. 3156–3164. 10.1021/acs.analchem.7b04424. 0003-2700. 5933435. 29381867.
  36. Guijas . Carlos . To . Andrew . Montenegro-Burke . J. Rafael . Domingo-Almenara . Xavier . Alipio-Gloria . Zaida . Kok . Bernard P. . Saez . Enrique . Alvarez . Nicole H. . Johnson . Kristen A. . Siuzdak . Gary . August 2022 . Drug-Initiated Activity Metabolomics Identifies Myristoylglycine as a Potent Endogenous Metabolite for Human Brown Fat Differentiation . Metabolites . en . 12 . 8 . 749 . 10.3390/metabo12080749 . 2218-1989 . 9415469 . 36005620. free .
  37. Domingo-Almenara. Xavier. Montenegro-Burke. J. Rafael. Guijas. Carlos. Majumder. Erica L.-W.. Benton. H. Paul. Siuzdak. Gary. 2019-03-05. Autonomous METLIN-Guided In-source Fragment Annotation for Untargeted Metabolomics. Analytical Chemistry. 91. 5. 3246–3253. 10.1021/acs.analchem.8b03126. 0003-2700. 6637741. 30681830.
  38. Xue. Jingchuan. Domingo-Almenara. Xavier. Guijas. Carlos. Palermo. Amelia. Rinschen. Markus M.. Isbell. John. Benton. H. Paul. Siuzdak. Gary. 2020-04-21. Enhanced in-Source Fragmentation Annotation Enables Novel Data Independent Acquisition and Autonomous METLIN Molecular Identification. Analytical Chemistry. 92. 8. 6051–6059. 10.1021/acs.analchem.0c00409. 32242660 . 8966047 . 0003-2700.
  39. Xue. Jingchuan. Derks. Rico J. E.. Hoang. Linh. Giera. Martin. Siuzdak. Gary. 2021-10-11. Proteomics with Enhanced In-Source Fragmentation/Annotation: Applying XCMS-EISA Informatics and Q-MRM High-Sensitivity Quantification. Journal of the American Society for Mass Spectrometry. 32 . 11 . 2644–2654 . 10.1021/jasms.1c00188. 34633184 . 238581609 . 1044-0305. 10245389.

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