University of Pittsburgh Department of Cell Biology
  • Research

    Nathan is an experimental analytical chemist who has pioneered advances in ion trap mass spectrometry, proteomics, and cloud computing. Early in his career, Nathan was focused on advancing a new type of mass spectrometer, the quadrupole ion trap, as an ultra-sensitive instrument capable of fully-automated on-line tandem mass spectrometry.  He was a principal architect and implementer of the “Ion Catcher Mass Spectrometry” software suite that introduced the use of computer generated scan functions and real-time data acquisition methods to enable tandem mass spectrometry on the chromatographic time scale.  These on-line data dependent acquisition methods were later commercialized by Finnigan Corp., are in widespread use today, have heavily influenced the evolution of LC-MS/MS instrumentation, and are fundamental to rapid growth of proteomics research. 

    After completing his graduate and postdoctoral studies, Nathan joined Merck and Co. Inc. to develop new methods to identify novel drug leads present in complex combinatorial libraries ([11467539],[11607705]).  He developed and distributed LibView, a software tool that compared ultra-complex spectra containing hundreds of thousands of drug like molecules to predictive models, enabling subtle changes in structure and abundance could be pin-pointed and identified. 

    Building on the LibView work, Nathan became fascinated with the unbiased analysis of ultra-complex mixtures and invented experimental and computation approach for comparing biological samples without the use of chemical labels or internal standards.  He invented “Differential Mass Spectrometry (dMS)” a label free approach for quantifying and identifying biologically relevant proteins in complex multi-factorial experiments([15481957]).  The dMS approach became the foundation for Merck’s proteomic biomarker discovery platform and was applied to large scale biomarker discovery efforts in in neuroscience, metabolic disorders, cardiovascular disease, and other key therapeutic areas([21475673],[20517885],[20028270],[20388904],[18785765],[19367703],[17070068]).  Nathan and colleagues industrialized the dMS approach which was later adopted by most major pharma companies as the Elucidator Proteomics Suite sold by Rosetta Biosoftware ([20095649]). 

    In 2011, Nathan joined the University of Pittsburgh with the goal of enabling large scale proteomics studies in an academic setting.  Because dMS requires highly specialized software and significant computational resources, Nathan partnered with Andrey Bondarenko (Infoclinika) to create a cloud-based dMS analysis platform that enables anyone with an internet connection to carry out large scale quantitative proteomics studies.   One major focus of Nathan’s laboratory is to develop personalized proteomics technologies that allow individuals to create and monitor their own health by tracking proteomic and metabolic profiles in urine and other clinically accessible bio-fluids.

    As the Scientific Director of the Biomedical Mass Spectrometry Center, Nathan seeks out academic collaborations in basic, translational, and clinical research that drive the development of new technologies and innovation, while advancing the use of mass spectrometry at the University of Pittsburgh.  Working with investigators from the departments of Cell Biology, Psychiatry, Pathology, Drug Discovery, and the Cancer Institute, our lab is involved in the elucidation of key players in biological pathways, the discovery of molecular targets for novel therapeutics, and identification and translation of candidate biomarkers ([25191796],[24798811],[25433904],[25423885],[24297176],[24019463]). 

    Mass spectrometry is highly collaborative and multi-disciplined field of study that brings together talented professionals with diverse backgrounds and expertise.  If you are passionate about science and enjoy working with others, mass spectrometry can be a great place.  Nathan’s lab works closely with companies in the technology and pharmaceutical sectors.   Current academic-industrial partnerships include collaborations with New Objective, Infoclinika, University of Washington, Scripps Florida, Bristol Myers Squibb, Novartis, and Merck.  Together, Nathan and colleagues are focused on advancing mass spectrometry based technologies and using them to solve important real world applications.
  • Publications

    1. Sweet RA, MacDonald ML, Kirkwood CM, Ding Y, Schempf T, Jones-Laughner J, Kofler J, Ikonomovic MD, Lopez OL, Garver ME, Fitz NF, Koldamova R, Yates NA. Apolipoprotein E*4 (APOE*4) Genotype Is Associated with Altered Levels of Glutamate Signaling Proteins and Synaptic Coexpression Networks in the Prefrontal Cortex in Mild to Moderate Alzheimer Disease.. Mol Cell Proteomics. 2016 Jul;15(7):2252-62. doi: 10.1074/mcp.M115.056580. PubMed PMID: 27103636;
    2. Hendrickson RC, Lee AY, Song Q, Liaw A, Wiener M, Paweletz CP, Seeburger JL, Li J, Meng F, Deyanova EG, Mazur MT, Settlage RE, Zhao X, Southwick K, Du Y, Holder D, Sachs JR, Laterza OF, Dallob A, Chappell DL, Snyder K, Modur V, King E, Joachim C, Bondarenko AY, Shearman M, Soper KA, Smith AD, Potter WZ, Koblan KS, Sachs AB, Yates NA. High Resolution Discovery Proteomics Reveals Candidate Disease Progression Markers of Alzheimer\'s Disease in Human Cerebrospinal Fluid. PLoS One. 2015 Aug 13;10(8):e0135365. doi: 10.1371/journal.pone.0135365. eCollection 2015. [link]
    3. Edmunds LR, Sharma L, Wang H, Kang A, d\'Souza S, Lu J, McLaughlin M, Dolezal JM, Gao X, Weintraub ST, Ding Y, Zeng X, Yates N, Prochownik EV. c-Myc and AMPK Control Cellular Energy Levels by Cooperatively Regulating Mitochondrial Structure and Function. PLoS One. 2015 Jul 31;10(7):e0134049. doi: 10.1371/journal.pone.0134049. eCollection 2015. [link]
    4. MacDonald ML, Ding Y, Newman J, Hemby S, Penzes P, Lewis DA, Yates NA, Sweet RA. Altered glutamate protein co-expression network topology linked to spine loss in the auditory cortex of schizophrenia. Biol Psychiatry. 2015 Jun 1;77(11):959-68. doi: 10.1016/j.biopsych.2014.09.006. Epub 2014 Nov 26. [link]
    5. Fang Q, Inanc B, Schamus S, Wang XH, Wei L, Brown AR, Svilar D, Sugrue KF, Goellner EM, Zeng X, Yates NA, Lan L, Vens C, Sobol RW. HSP90 regulates DNA repair via the interaction between XRCC1 and DNA polymerase β. Nat Commun. 2014 Nov 26;5:5513. doi: 10.1038/ncomms6513. [link]
    6. Strickler AG, Vasquez JG, Yates N, Ho J. Potential diagnostic significance of HSP90, ACS/TMS1, and L-plastin in the identification of melanoma. Melanoma Res. 2014 Dec;24(6):535-44. doi: 10.1097/CMR.0000000000000115. [link]
    7. Miedel MT, Zeng X, Yates NA, Silverman GA, Luke CJ. Isolation of serpin-interacting proteins in C. elegans using protein affinity purification. Methods. 2014 Aug 1;68(3):536-41. doi: 10.1016/j.ymeth.2014.04.019. Epub 2014 May 2. [link]
    8. Wang W, Choi BK, Li W, Lao Z, Lee AY, Souza SC, Yates NA, Kowalski T, Pocai A, Cohen LH. Quantification of intact and truncated stromal cell-derived factor-1α in circulation by immunoaffinity enrichment and tandem mass spectrometry. J Am Soc Mass Spectrom. 2014 Apr;25(4):614-25. doi: 10.1007/s13361-013-0822-7. Epub 2014 Feb 6. [link]
    9. Chappell DL, Lee AY, Castro-Perez J, Zhou H, Roddy TP, Lassman ME, Shankar SS, Yates NA, Wang W, Laterza OF. An ultrasensitive method for the quantitation of active and inactive GLP-1 in human plasma via immunoaffinity LC-MS/MS. Bioanalysis. 2014 Jan;6(1):33-42. doi: 10.4155/bio.13.280. [link]
    10. Antony ML, Lee J, Hahm ER, Kim SH, Marcus AI, Kumari V, Ji X, Yang Z, Vowell CL, Wipf P, Uechi GT, Yates NA, Romero G, Sarkar SN, Singh SV. Growth arrest by the antitumor steroidal lactone withaferin A in human breast cancer cells is associated with down-regulation and covalent binding at cysteine 303 of β-tubulin. J Biol Chem. 2014 Jan 17;289(3):1852-65. doi: 10.1074/jbc.M113.496844. Epub 2013 Dec 2. [link]
    11. Huang F, Zeng X, Kim W, Balasubramani M, Fortian A, Gygi SP, Yates NA, Sorkin A. Lysine 63-linked polyubiquitination is required for EGF receptor degradation. Proc Natl Acad Sci U S A. 2013 Sep 24;110(39):15722-7. doi: 10.1073/pnas.1308014110. Epub 2013 Sep 9. [link]
    12. Wang W, Walker ND, Zhu LJ, Wu W, Ge L, Gutstein DE, Yates NA, Hendrickson RC, Ogletree ML, Cleary M, Opiteck GJ, Chen Z. Quantification of circulating D-dimer by peptide immunoaffinity enrichment and tandem mass spectrometry. Anal Chem. 2012 Aug 7;84(15):6891-8. doi: 10.1021/ac301494d. Epub 2012 Jul 19. [link]
    13. Conway JP, Johns DG, Wang SP, Walker ND, McAvoy TA, Zhou H, Zhao X, Previs SF, Roddy TP, Hubbard BK, Yates NA, Hendrickson RC. Measuring H(2)(18)O tracer incorporation on a QQQ-MS platform provides a rapid, transferable screening tool for relative protein synthesis. J Proteome Res. 2012 Mar 2;11(3):1591-7. doi: 10.1021/pr2007494. Epub 2012 Feb 10. [link]
    14. Lee AY, Yates NA, Ichetovkin M, Deyanova E, Southwick K, Fisher TS, Wang W, Loderstedt J, Walker N, Zhou H, Zhao X, Sparrow CP, Hubbard BK, Rader DJ, Sitlani A, Millar JS, Hendrickson RC. Measurement of fractional synthetic rates of multiple protein analytes by triple quadrupole mass spectrometry. Clin Chem. 2012 Mar;58(3):619-27. doi: 10.1373/clinchem.2011.172429. Epub 2012 Jan 16. [link]
    15. Chen F, Lam R, Shaywitz D, Hendrickson RC, Opiteck GJ, Wishengrad D, Liaw A, Song Q, Stewart AJ, Cummings CE, Beals C, Yarasheski KE, Reicin A, Ruddy M, Hu X, Yates NA, Menetski J, Herman GA. Evaluation of early biomarkers of muscle anabolic response to testosterone. J Cachexia Sarcopenia Muscle. 2011 Mar;2(1):45-56. Epub 2011 Feb 26. [link]
    16. Falick AM, Lane WS, Lilley KS, MacCoss MJ, Phinney BS, Sherman NE, Weintraub ST, Witkowska HE, Yates NA. ABRF-PRG07: advanced quantitative proteomics study. J Biomol Tech. 2011 Apr;22(1):21-6. [link]
    17. Friedman DB, Andacht TM, Bunger MK, Chien AS, Hawke DH, Krijgsveld J, Lane WS, Lilley KS, MacCoss MJ, Moritz RL, Settlage RE, Sherman NE, Weintraub ST, Witkowska HE, Yates NA, Turck CW. The ABRF Proteomics Research Group studies: educational exercises for qualitative and quantitative proteomic analyses. Proteomics. 2011 Apr;11(8):1371-81. doi: 10.1002/pmic.201000736. Epub 2011 Mar 11. [link]
    18. Zhao X, Southwick K, Cardasis HL, Du Y, Lassman ME, Xie D, El-Sherbeini M, Geissler WM, Pryor KD, Verras A, Garcia-Calvo M, Shen DM, Yates NA, Pinto S, Hendrickon RC. Peptidomic profiling of human cerebrospinal fluid identifies YPRPIHPA as a novel substrate for prolylcarboxypeptidase. Proteomics. 2010 Aug;10(15):2882-6. doi: 10.1002/pmic.201000145. [link]
    19. Mazur MT, Cardasis HL, Spellman DS, Liaw A, Yates NA, Hendrickson RC. Quantitative analysis of intact apolipoproteins in human HDL by top-down differential mass spectrometry. Proc Natl Acad Sci U S A. 2010 Apr 27;107(17):7728-33. doi: 10.1073/pnas.0910776107. Epub 2010 Apr 13. [link]
    20. Paweletz CP, Wiener MC, Bondarenko AY, Yates NA, Song Q, Liaw A, Lee AY, Hunt BT, Henle ES, Meng F, Sleph HF, Holahan M, Sankaranarayanan S, Simon AJ, Settlage RE, Sachs JR, Shearman M, Sachs AB, Cook JJ, Hendrickson RC. Application of an end-to-end biomarker discovery platform to identify target engagement markers in cerebrospinal fluid by high resolution differential mass spectrometry. J Proteome Res. 2010 Mar 5;9(3):1392-401. doi: 10.1021/pr900925d. [link]
    21. Sietsema KE, Meng F, Yates NA, Hendrickson RC, Liaw A, Song Q, Brass EP, Ulrich RG. Potential biomarkers of muscle injury after eccentric exercise. Biomarkers. 2010 May;15(3):249-58. doi: 10.3109/13547500903502802. [link]

     

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