Neil L. Kelleher
Walter and Mary E. Glass Professor
Our laboratory has three main areas of research: custom instrumentation for Fourier Transform Mass Spectrometry (FTMS), Nuclear Signaling and Natural Products. More specifically, our main interests lie in the enzymology of natural product biosynthesis, mass spectrometric-based studies of the "Histone Code," and development of Fourier Transform Mass Spectrometry (FTMS) for Top Down Proteomics (i.e. analyzing intact proteins directly; no proteases).
A core activity is measuring chemical modifications to proteins in both hypothesis-driven and discovery modes. Our pioneering efforts in "Top Down" proteomics involve fragmenting intact protein ions in the gas phase and developing custom bioinformatics to characterize unexpected post-translational modifications (PTMs) in methane-producing microbes, yeast, and human cancer cells. In both human cell biology and antibiotic biosynthesis, key proteins harbor over 20 PTMs that present a "code" of biological logic written in the language of protein modifications. We construct, automate, and apply custom mass spectrometry and algorithms to detect and decode this logic.
Mass Spectrometry Imaging and Identification of Peptides Associated with Cephalic Ganglia Regeneration in Schmidtea mediterranea. Ong T-H, Romanova EV, Roberts-Galbraith RH, Yang N, Zimmerman TA, Collins JJ, Lee JE, Kelleher NL, Newmark PA, and Sweedler JV. Journal of Biological Chemistry. 2016 April 8;291(15):8109-8120.
Quantitation and Identification of Thousands of Human Proteoforms below 30 kDa. Durbin KR, Fornelli L, Fellers RT, Doubleday PF, Narita M, and Kelleher NL. Journal of Proteome Research. 2016 March 4;15(3):976-982.
Unabridged Analysis of Human Histone H3 by Differential Top-Down Mass Spectrometry Reveals Hypermethylated Proteoforms from MMSET/NSD2 Overexpression. Zheng Y, Fornelli L, Compton PD, Sharma S, Canterbury J, Mullen C, Zabrouskov V, Fellers RT, Thomas PM, Licht JD, Senko MW, and Kelleher NL. Molecular & Cellular Proteomics. 2016 March 1;15(3):776-790.
An informatic framework for decoding protein complexes by top-down mass spectrometry. Skinner OS, Havugimana PC, Haverland NA, Fornelli L, Early BP, Greer JB, Fellers RT, Durbin KR, Do Vale LHF, Melani RD, Seckler HS, Nelp MT, Belov ME, Horning SR, Makarov AA, LeDuc RD, Bandarian V, Compton PD, and Kelleher NL. Nature Methods. 2016 March;13(3):237-240.
Metabologenomics: Correlation of Microbial Gene Clusters with Metabolites Drives Discovery of a Nonribosomal Peptide with an Unusual Amino Acid Monomer. Goering AW, McClure RA, Doroghazi JR, Albright JC, Haverland NA, Zhang Y, Ju K-S, Thomson RJ, Metcalf WW, and Kelleher NL. ACS Central Science. 2016 February 24;2(2):99-108.
Antigen clasping by two antigen-binding sites of an exceptionally specific antibody for histone methylation. Hattori T, Lai D, Dementieva IS, Montaño SP, Kurosawa K, Zheng Y, Akin LR, Swist-Rosowska KM, Grzybowski AT, Koide A, Krajewski K, Strahl BD, Kelleher NL, Ruthenburg AJ, and Koide S. PNAS. 2016 February 23;113(8):2092-2097.
Targeted analysis of recombinant NF kappa B (RelA/p65) by denaturing and native top down mass spectrometry. Savaryn JP, Skinner OS, Fornelli L, Fellers RT, Compton PD, Terhune SS, Abecassis MM, and Kelleher NL. Journal of Proteomics. 2016 February 16;134:76-84.
A Method for Label-Free, Differential Top-Down Proteomics. Ntai I, Toby TK, LeDuc RD, and Kelleher NL. Methods in Molecular Biology. 2016 February 12;1410:121-133.
Integrated Bottom-Up and Top-Down Proteomics of Patient-Derived Breast Tumor Xenografts. Ntai I, LeDuc RD, Fellers RT, Erdmann-Gilmore P, Davies SR, Rumsey J, Early BP, Thomas PM, Li S, Compton PD, Ellis MJC, Ruggles KV, Fenyö D, Boja ES, Rodriguez H, Townsend RR, and Kelleher NL. Molecular & Cellular Proteomics. 2016 January 1;15(1):45-56.
Mass Spectrometry and Antibody-Based Characterization of Blood Vessels from Brachylophosaurus canadensis. Cleland TP, Schroeter ER, Zamdborg L, Zheng W, Lee JE, Tran JC, Bern M, Duncan MB, Lebleu VS, Ahlf DR, Thomas PM, Kalluri R, Kelleher NL, and Schweitzer MH. Journal of Proteome Research. 2015 December 4;14(12):5252-5262.
Evolution of translation machinery in recoded bacteria enables multi-site incorporation of nonstandard amino acids. Amiram M, Haimovich AD, Fan C, Wang Y-S, Aerni H-R, Ntai I, Moonan DW, Ma NJ, Rovner AJ, Hong SH, Kelleher NL, Goodman AL, Jewett MC, Söll D, Rinehart J, and Isaacs FJ. Nature Biotechnology. 2015 December;33(12):1272-1279.
Mechanism of Inactivation of GABA Aminotransferase by (E)- and (Z)-(1S,3S)-3-Amino-4-fluoromethylenyl-1-cyclopentanoic Acid. Lee H, Le HV, Wu R, Doud E, Sanishvili R, Kellie JF, Compton PD, Pachaiyappan B, Liu D, Kelleher NL, and Silverman RB. ACS Chemical Biology. 2015 September 18;10(9):2087-2098.
Reducing protein oxidation in low-flow electrospray enables deeper investigation of proteoforms by top down proteomics. Kim K, Compton PD, Toby TK, Thomas PM, Wilkins JT, Mutharasan RK, and Kelleher NL. EuPA Open Proteomics. 2015 September;8:40-47.
Large-Scale Metabolomics Reveals a Complex Response of Aspergillus nidulans to Epigenetic Perturbation. Albright JC, Henke MT, Soukup AA, McClure RA, Thomson RJ, Keller NP, and Kelleher NL. ACS Chemical Biology. 2015 June 19;10(6):1535-1541.
View all publications by Neil L. Kelleher listed in the National Library of Medicine (PubMed). Current and former IBiS students in blue.