University of Pittsburgh Department of Cell Biology

Yates Lab

Yates and colleagues are focused on advancing mass spectrometry as an important bioanalytical tool for life sciences research and drug development. In contrast to antibody-based methods that measure one protein at a time, mass spectrometry allows thousands of proteins to be examined together with unprecedented speed and sensitivity. One of their strategies, differential mass spectrometry, couples state-of-the-art, high-resolution Fourier-transform mass spectrometry with cloud-computing image processing tools to identify and quantify proteins that exhibit a statistically significant change in abundance as a function of time, treatment, or condition. This new quantitative proteomics technique creates many avenues for studying the nature and function of proteins in cells, tissue, or clinically accessible bio fluids. Importantly, mass spectrometry also provides a direct path for translating these discoveries into new assays or diagnostic tests that measure biologically relevant proteins with absolute molecular specificity.

This work is highly multidisciplinary, bringing together people with expertise in biochemistry, high-resolution mass spectrometry, and informatics; with collaborative publications related to Cancer, Schizophrenia, Alzheimer's disease, and Metabolic Disorders. Working closely with the pharmaceutical industry, we have a special interest in proteomic methods that identify novel drug-target interactions and elucidate novel on/off-target effects of medicines. Driving experimental innovations towards commercial development is a key objective of the lab and we actively partner with companies to make new technologies accessible to the broader scientific community.

  1. Bell-Temin H, Yousefzadeh MJ, Bondarenko A, Quarles E, Jones-Laughner J, Robbins PD, Ladiges W, Niedernhofer LJ, Yates NA. Measuring biological age in mice using differential mass spectrometry.. Aging (Albany NY). 2019 Feb 11;11(3):1045-1061. doi: 10.18632/aging.101810. PubMed PMID: 30745468;
  2. Khetarpal SA, Zeng X, Millar JS, Vitali C, Somasundara AVH, Zanoni P, Landro JA, Barucci N, Zavadoski WJ, Sun Z, de Haard H, Toth IV, Peloso GM, Natarajan P, Cuchel M, Lund-Katz S, Phillips MC, Tall AR, Kathiresan S, DaSilva-Jardine P, Yates NA, Rader DJ. A human APOC3 missense variant and monoclonal antibody accelerate apoC-III clearance and lower triglyceride-rich lipoprotein levels.. Nat Med. 2017 Sep;23(9):1086-1094. doi: 10.1038/nm.4390. PubMed PMID: 28825717;
  3. 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;
  4. 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]
  5. 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]
  6. 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]
  7. 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]
  8. 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]
  9. 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]
  10. 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]
  11. 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]
  12. 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]
  13. 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]
  14. 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]
  15. 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]
  16. 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]
  17. 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]
  18. 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]
  19. 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]
  20. 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]
  21. 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]
  22. 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]
  23. 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]
Postal Address:
University of Pittsburgh
Department of Cell Biology
Biomedial Science Tower 3, 9043B
Telephone:  732-718-9739