Gary Siuzdak

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Gary Siuzdak
SizudakDC7.jpg
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.

Contents

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 received and gave the Michael L. Gross Award [34] lecture in 2019 and was made a Lifetime Honorary Fellow from the Metabolomics Society [35] . 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). [36]

Notable research

From 1994 to the present the Siuzdak lab has been working on activity metabolomics. [1] [3] [4] [5] [9] [12] [37] [15] [38] [39] using liquid chromatography mass spectrometry-based metabolomics to identify metabolites that alter phenotype. [1] [3] [4] [5] [37] [15] [38] [39] [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] [40]

From the early 2000s [41] [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 May 2025) has over 930,000 molecular standards [42] with experimental tandem mass spectrometry data. [14] [13] [43] 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 [44] and METLIN, [12] [41] developed Enhanced In-Source Fragmentation/Annotation (EISA) [27] to facilitate the fragmentation, identification, and quantification (via Q-MRM) [28] [45] of molecules without the use of tandem mass spectrometry.

References

  1. 1 2 3 4 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. 1 2 3 4 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. 1 2 3 4 5 6 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. 1 2 3 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. 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. 1 2 3 4 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. 1 2 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. 1 2 3 4 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. 1 2 3 4 5 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. 1 2 3 4 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. 1 2 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. 1 2 3 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. 1 2 "Faculty Page, Gary Siuzdak". scripps.edu. Retrieved 22 May 2019.
  19. 1 2 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. 1 2 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. 1 2 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. 1 2 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. 1 2 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. "Siuzdak to Deliver the 2019 M.L. Gross Award Lecture | Department of Chemistry | Nebraska". chem.unl.edu. Retrieved 2025-07-23.
  35. "Honorary Fellowships – Metabolomics Society". metabolomicssociety.org. Retrieved 2025-07-23.
  36. "Interview with Dr. Gary Siuzdak". MetaboNews, Issue 13 - September 2012. Retrieved 22 May 2019.
  37. 1 2 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.
  38. 1 2 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.
  39. 1 2 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.
  40. 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.
  41. 1 2 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.
  42. Uritboonthai, Winnie; Hoang, Linh; Aisporna, Aries; Giera, Martin; Siuzdak, Gary (2025-05-14). "The Dark Metabolome/Lipidome and In-Source Fragmentation". Analytical Science Advances. 6 (1): e70012. doi:10.1002/ansa.70012. ISSN   2628-5452. PMC   12077755 . PMID   40371267.
  43. 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.
  44. 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.
  45. 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.