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.
Oncogene-induced cellular senescence elicits an anti-Warburg effect. Li M, Durbin KR, Sweet SMM, Tipton JD, Zheng Y, and Kelleher NL. Proteomics. 2013 September;13(17):2585-2596.
Complete Protein Characterization Using Top-Down Mass Spectrometry and Ultraviolet Photodissociation. Shaw JB, Li W, Holden DD, Zhang Y, Griep-Raming J, Fellers RT, Early BP, Thomas PM, Kelleher NL, and Brodbelt JS. Journal of the American Chemical Society. 2013 August 28;135(34):12646-12651.
Measurement of acetylation turnover at distinct lysines in human histones identifies long-lived acetylation sites. Zheng Y, Thomas PM, and Kelleher NL. Nature Communications. 2013 July 29;4:2203.
Proteomics Guided Discovery of Flavopeptins: Anti-proliferative Aldehydes Synthesized by a Reductase Domain-Containing Non-ribosomal Peptide Synthetase. Chen Y, McClure RA, Zheng Y, Thomson RJ, and Kelleher NL. Journal of the American Chemical Society. 2013 July 17;135(28):10449-10456.
Discovery of the Antibiotic Phosacetamycin via a New Mass Spectrometry-Based Method for Phosphonic Acid Detection. Evans BS, Zhao C, Gao J, Evans CM, Ju K-S, Doroghazi JR, van der Donk WA, Kelleher NL, and Metcalf WW. ACS Chemical Biology. 2013 May 17;8(5):908-913.
EZH2 Is Required for Germinal Center Formation and Somatic EZH2 Mutations Promote Lymphoid Transformation. Béguelin W, Popovic R, Teater M, Jiang Y, Bunting KL, Rosen M, Shen H, Yang SN, Wang L, Ezponda T, Martinez-Garcia E, Zhang H, Zheng Y, Verma SK, McCabe MT, Ott HM, Van Aller GS, Kruger RG, Liu Y, McHugh CF, Scott DW, Chung YR, Kelleher N, Shaknovich R, Creasy CL, Gascoyne RD, Wong K-K, Cerchietti L, Levine RL, Abdel-Wahab O, Licht JD, Elemento O, and Melnick AM. Cancer Cell. 2013 May 13;23(5):677-692.
Metabolic Perturbation of an Essential Pathway: Evaluation of a Glycine Precursor of Coenzyme A. Rothmann M, Kang M, Villa R, Ntai I, La Clair JJ, Kelleher NL, Chapman E, and Burkart MD. Journal of the American Chemical Society. 2013 April 24;135(16):5962-5965.
Differential lysine acetylation profiles of Erwinia amylovora strains revealed by proteomics. Wu X, Vellaichamy A, Wang D, Zamdborg L, Kelleher NL, Huber SC, and Zhao Y. Journal of Proteomics. 2013 February 21;79:60-71.
Top Down Proteomics of Human Membrane Proteins from Enriched Mitochondrial Fractions. Catherman AD, Li M, Tran JC, Durbin KR, Compton PD, Early BP, Thomas PM, and Kelleher NL. Analytical Chemistry. 2013 February 5;85(3):1880-1888.
Quantitative Peptidomics for Discovery of Circadian-Related Peptides from the Rat Suprachiasmatic Nucleus. Lee JE, Zamdborg L, Southey BR, Atkins N, Mitchell JW, Li M, Gillette MU, Kelleher NL, and Sweedler JV. Journal of Proteome Research. 2013 February 1;12(2):585-593.
View all publications by Neil L. Kelleher listed in the National Library of Medicine (PubMed). Current and former IBiS students in blue.