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.
In Vitro Reconstruction of Nonribosomal Peptide Biosynthesis Directly from DNA Using Cell-Free Protein Synthesis. Goering AW, Li J, McClure RA, Thomson RJ, Jewett MC, and Kelleher NL. ACS Synthetic Biology. 2017 January 20;6(1):39-44.
Characterization of Methanobactin from Methylosinus sp. LW4. Kenney GE, Goering AW, Ross MO, DeHart CJ, Thomas PM, Hoffman BM, Kelleher NL, and Rosenzweig AC. Journal of the American Chemical Society. 2016 September 7;138(35):11124-11127.
A researcher's guide to mass spectrometry-based proteomics. Savaryn JP, Toby TK, and Kelleher NL. Proteomics. 2016 September;16(18):2435-2443.
New Aspercryptins, Lipopeptide Natural Products, Revealed by HDAC Inhibition in Aspergillus nidulans. Henke MT, Soukup AA, Goering AW, McClure RA, Thomson RJ, Keller NP, and Kelleher NL. ACS Chemical Biology. 2016 August 19;11(8):2117-2123.
Modern mass spectrometry for synthetic biology and structure-based discovery of natural products. Henke MT and Kelleher NL. Natural Product Reports. 2016 August 1;33(8):942-950.
Epiproteomics: quantitative analysis of histone marks and codes by mass spectrometry. Zheng Y, Huang X, and Kelleher NL. Current Opinion in Chemical Biology. 2016 August;33:142-150.
Mapping Proteoforms and Protein Complexes From King Cobra Venom Using Both Denaturing and Native Top-down Proteomics. Melani RD, Skinner OS, Fornelli L, Domont GB, Compton PD, and Kelleher NL. Molecular & Cellular Proteomics. 2016 July 1;15(7):2423-2434.
Comparative top down proteomics of peripheral blood mononuclear cells from kidney transplant recipients with normal kidney biopsies or acute rejection. Savaryn JP, Toby TK, Catherman AD, Fellers RT, LeDuc RD, Thomas PM, Friedewald JJ, Salomon DR, Abecassis MM, and Kelleher NL. Proteomics. 2016 July;16(14):2048-2058.
Progress in Top-Down Proteomics and the Analysis of Proteoforms. Toby TK, Fornelli L, and Kelleher NL. Annual Review of Analytical Chemistry. 2016 June;9:499-519.
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.
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.
View all publications by Neil L. Kelleher listed in the National Library of Medicine (PubMed). Current and former IBiS students in blue.