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Gary Siuzdak

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Gary Siuzdak
BornDecember 29, 1961
Scientific career
FieldsAnalytical 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][7] (a termed coined in 2019[8]), and mass spectrometry.[9][10][11][12][13][14] His lab discovered indole-3-propionic acid as a gut bacteria derived metabolite in 2009.[15][16][17] He is currently the Professor and Director of The Center for Metabolomics and Mass Spectrometry at Scripps Research in La Jolla, California.[18] Siuzdak has also made contributions to virus analysis,[19][20] viral structural dynamics,[21][22][23] as well as developing mass spectrometry imaging technology using nanostructured surfaces.[11][24] The Siuzdak lab is also responsible for creating the research tools eXtensible Computational Mass Spectrometry (XCMS),[9][25] METLIN,[13] METLIN Neutral Loss[26] and Q-MRM.[27][28][29] As of January 2021,[30] 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[31] to perform multi-photon ionization mass spectrometry experiments and occasionally competed in powerlifting.[32] At Dartmouth he received his Ph.D. in Physical Chemistry (March 29, 1990) and on April 1, 1990, started at Scripps Research.[18] In 2017 Siuzdak received an honorary doctorate (with Emmanuelle Charpentier) from Umeå University[33] 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).[34]

Notable research

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From 1994 to the present the Siuzdak lab has been working on activity metabolomics.[1][3][4][5][9][12][35][15][36][37] using liquid chromatography mass spectrometry-based metabolomics to identify metabolites that alter phenotype.[1][3][4][5][35][15][36][37][12] His initial efforts with Richard Lerner,[4] 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),[4] 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.[4][1][3] Another notable activity metabolomics effort with Oscar Yanes (Spain) identified[5] 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.[19] 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.[20]

In 1999, the Siuzdak lab described the use of nanostructures to enhance desorption/ionization on porous silicon of small molecules (DIOS),[10] 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),[11] it is also known as Nanostructure Imaging Mass Spectrometry (NIMS) because of its expanded application to imaging.[11][24]

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.[9][38]

From the early 2000s[39][12] 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.[14][13][40] METLIN is unique with respect to its size, as other databases are over an order of magnitude smaller,[13] 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[41] and METLIN,[12][39] developed Enhanced In-Source Fragmentation/Annotation (EISA)[27] to facilitate the fragmentation, identification, and quantification (via Q-MRM)[28][42] of molecules without the use of tandem mass spectrometry.

References

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  1. ^ a b c d 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. 36 (4): 316–320. doi:10.1038/nbt.4101. ISSN 1546-1696. PMC 5937131. PMID 29621222.
  2. ^ Johnson, Caroline H.; Ivanisevic, Julijana; Siuzdak, Gary (July 2016). "Metabolomics: beyond biomarkers and towards mechanisms". Nature Reviews Molecular Cell Biology. 17 (7): 451–459. doi:10.1038/nrm.2016.25. ISSN 1471-0080. PMC 5729912. PMID 26979502.
  3. ^ a b c d Rinschen, Markus M.; Ivanisevic, Julijana; Giera, Martin; Siuzdak, Gary (June 2019). "Identification of bioactive metabolites using activity metabolomics". Nature Reviews Molecular Cell Biology. 20 (6): 353–367. doi:10.1038/s41580-019-0108-4. ISSN 1471-0080. PMC 6613555. PMID 30814649.
  4. ^ a b c d e f Cravatt, BF; Prospero-Garcia, O; Siuzdak, G; Gilula, NB; Henriksen, SJ; Boger, DL; Lerner, RA (9 June 1995). "Chemical characterization of a family of brain lipids that induce sleep". Science. 268 (5216): 1506–9. Bibcode:1995Sci...268.1506C. doi:10.1126/science.7770779. PMID 7770779.
  5. ^ a b c d 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. 6 (6): 411–417. doi:10.1038/nchembio.364. ISSN 1552-4469. PMC 2873061. PMID 20436487.
  6. ^ 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. 91 (20): 9505–9508. Bibcode:1994PNAS...91.9505L. doi:10.1073/pnas.91.20.9505. ISSN 0027-8424. PMC 44841. PMID 7937797.
  7. ^ 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. doi:10.1126/scisignal.abf6584. PMC 8757460. PMID 34582249.
  8. ^ Rinschen, Markus M.; Ivanisevic, Julijana; Giera, Martin; Siuzdak, Gary (June 2019). "Identification of bioactive metabolites using activity metabolomics". Nature Reviews Molecular Cell Biology. 20 (6): 353–367. doi:10.1038/s41580-019-0108-4. ISSN 1471-0080. PMC 6613555. PMID 30814649.
  9. ^ a b c d 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. doi:10.1021/ac051437y. ISSN 0003-2700. PMID 16448051.
  10. ^ a b Wei, Jing; Buriak, Jillian M.; Siuzdak, Gary (May 1999). "Desorption–ionization mass spectrometry on porous silicon". Nature. 399 (6733): 243–246. Bibcode:1999Natur.399..243W. doi:10.1038/20400. ISSN 1476-4687. PMID 10353246. S2CID 4314372.
  11. ^ a b c d 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. 449 (7165): 1033–1036. Bibcode:2007Natur.449.1033N. doi:10.1038/nature06195. ISSN 1476-4687. PMID 17960240. S2CID 4404703.
  12. ^ a b c d e 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. doi:10.1021/acs.analchem.7b04424. ISSN 0003-2700. PMC 5933435. PMID 29381867.
  13. ^ a b c d 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): 953–954. doi:10.1038/s41592-020-0942-5. ISSN 1548-7105. PMC 8802982. PMID 32839599.
  14. ^ a b Giera, Martin; Yanes, Oscar; Siuzdak, Gary (2022-01-04). "Metabolite discovery: Biochemistry's scientific driver". Cell Metabolism. 34 (1): 21–34. doi:10.1016/j.cmet.2021.11.005. ISSN 1550-4131. PMC 10131248. PMID 34986335. S2CID 245729571.
  15. ^ a b c 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. 106 (10): 3698–3703. Bibcode:2009PNAS..106.3698W. doi:10.1073/pnas.0812874106. ISSN 0027-8424. PMC 2656143. PMID 19234110.
  16. ^ Guijas, Carlos; Horton, Lucy E.; Hoang, Linh; Domingo-Almenara, Xavier; Billings, Elizabeth M.; Ware, Brian C.; Sullivan, Brian; Siuzdak, Gary (July 2022). "Microbial Metabolite 3-Indolepropionic Acid Mediates Immunosuppression". Metabolites. 12 (7): 645. doi:10.3390/metabo12070645. ISSN 2218-1989. PMC 9317520. PMID 35888769.
  17. ^ Serger, Elisabeth; Luengo-Gutierrez, Lucia; Chadwick, Jessica S.; Kong, Guiping; Zhou, Luming; Crawford, Greg; Danzi, Matt C.; Myridakis, Antonis; Brandis, Alexander; Bello, Adesola Temitope; Müller, Franziska; Sanchez-Vassopoulos, Alexandros; De Virgiliis, Francesco; Liddell, Phoebe; Dumas, Marc Emmanuel (July 2022). "The gut metabolite indole-3 propionate promotes nerve regeneration and repair". Nature. 607 (7919): 585–592. Bibcode:2022Natur.607..585S. doi:10.1038/s41586-022-04884-x. ISSN 1476-4687. PMID 35732737.
  18. ^ a b "Faculty Page, Gary Siuzdak". scripps.edu. Retrieved 22 May 2019.
  19. ^ a b 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. 3 (1): 45–48. doi:10.1016/S1074-5521(96)90083-6. ISSN 1074-5521. PMID 8807827.
  20. ^ a b 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. doi:10.1002/1521-3773(20010202)40:3<541::AID-ANIE541>3.0.CO;2-K. ISSN 1521-3773.
  21. ^ 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. 273 (2): 673–676. doi:10.1074/jbc.273.2.673. ISSN 0021-9258. PMID 9422714.
  22. ^ 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. 95 (12): 6774–6778. Bibcode:1998PNAS...95.6774L. doi:10.1073/pnas.95.12.6774. ISSN 0027-8424. PMC 22631. PMID 9618488.
  23. ^ 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. 6 (2): 114–116. doi:10.1038/5799. ISSN 1545-9985. PMID 10048920. S2CID 1756648.
  24. ^ a b Kurczy, ME; Northen, TR; Trauger, SA; Siuzdak, G (2015). "Nanostructure Imaging Mass Spectrometry: The Role of Fluorocarbons in Metabolite Analysis and Yoctomole Level Sensitivity". Mass Spectrometry Imaging of Small Molecules. Methods in Molecular Biology. Vol. 1203. pp. 141–9. doi:10.1007/978-1-4939-1357-2_14. ISBN 978-1-4939-1356-5. PMC 4755109. PMID 25361674.
  25. ^ Domingo-Almenara, Xavier; Siuzdak, Gary (2020), Li, Shuzhao (ed.), "Metabolomics Data Processing Using XCMS", Computational Methods and Data Analysis for Metabolomics, Methods in Molecular Biology, vol. 2104, New York, NY: Springer US, pp. 11–24, doi:10.1007/978-1-0716-0239-3_2, ISBN 978-1-0716-0239-3, PMID 31953810, S2CID 210709390, retrieved 2023-07-13
  26. ^ Aisporna, Aries; Benton, H. Paul; Galano, Jean Marie; Giera, Martin; Siuzdak, Gary (2021-04-04). "METLIN Neutral Loss Database Enhances Similarity Analysis": 2021.04.02.438066. doi:10.1101/2021.04.02.438066. S2CID 233175525. {{cite journal}}: Cite journal requires |journal= (help)
  27. ^ a b 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. doi:10.1021/acs.analchem.0c00409. ISSN 0003-2700. PMC 8966047. PMID 32242660.
  28. ^ a b 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. doi:10.1021/acs.analchem.1c01246. hdl:1887/3243130. ISSN 0003-2700. PMC 8762722. PMID 34313111.
  29. ^ 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. doi:10.1021/jasms.1c00188. ISSN 1044-0305. PMC 10245389. PMID 34633184. S2CID 238581609.
  30. ^ 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): 1376–1418. doi:10.1038/s41596-020-00455-4. ISSN 1750-2799. OSTI 1774918. PMC 10357461. PMID 33483720. S2CID 231687415.
  31. ^ 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. doi:10.1021/j100374a038. ISSN 0022-3654.
  32. ^ Scandura, Mike (30 Dec 1987). "Weightlifting the right way good for Siuzdak". The Evening Times (Pawtucket, R.I.).
  33. ^ "Biochemist and metabolomics researcher take honorary roles at Umeå University". www.umu.se. Retrieved 2020-10-21.
  34. ^ "Interview with Dr. Gary Siuzdak". MetaboNews, Issue 13 - September 2012. Retrieved 22 May 2019.
  35. ^ a b 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. 8 (3): 232–234. doi:10.1038/nchembio.767. ISSN 1552-4469. PMC 3567618. PMID 22267119.
  36. ^ a b 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. 14 (1): 22–28. doi:10.1038/nchembio.2517. ISSN 1552-4469. PMC 5928791. PMID 29131145.
  37. ^ a b 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. 13 (648). doi:10.1126/scisignal.abb2490. ISSN 1945-0877. PMC 7580877. PMID 32900879.
  38. ^ 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. doi:10.1021/ac300698c. ISSN 0003-2700. PMC 3703953. PMID 22533540.
  39. ^ a b 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. 27 (6): 747–751. doi:10.1097/01.ftd.0000179845.53213.39. ISSN 0163-4356. PMID 16404815. S2CID 14774455.
  40. ^ 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. 12 (8): 749. doi:10.3390/metabo12080749. ISSN 2218-1989. PMC 9415469. PMID 36005620.
  41. ^ 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. doi:10.1021/acs.analchem.8b03126. ISSN 0003-2700. PMC 6637741. PMID 30681830.
  42. ^ 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. doi:10.1021/jasms.1c00188. ISSN 1044-0305. PMC 10245389. PMID 34633184. S2CID 238581609.
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