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.
A roadmap for natural product discovery based on large-scale genomics and metabolomics. Doroghazi JR, Albright JC, Goering AW, Ju K-S, Haines RR, Tchalukov KA, Labeda DP, Kelleher NL, and Metcalf WW. Nature Chemical Biology. 2014 November;10(11):963-968.
Site-specific human histone H3 methylation stability: fast K4me3 turnover. Zheng Y, Tipton JD, Thomas PM, Kelleher NL, and Sweet SMM. Proteomics. 2014 October;14(19):2190-2199.
Histone Methyltransferase MMSET/NSD2 Alters EZH2 Binding and Reprograms the Myeloma Epigenome through Global and Focal Changes in H3K36 and H3K27 Methylation. Popovic R, Martinez-Garcia E, Giannopoulou EG, Zhang Q, Zhang Q, Ezponda T, Shah MY, Zheng Y, Will CM, Small EC, Hua Y, Bulic M, Jiang Y, Carrara M, Calogero RA, Kath WL, Kelleher NL, Wang J-P, Elemento O, and Licht JD. PLoS Genetics. 2014 September 4;10(9):e1004566.
The C-Score: A Bayesian Framework to Sharply Improve Proteoform Scoring in High-Throughput Top Down Proteomics. LeDuc RD, Fellers RT, Early BP, Greer JB, Thomas PM, and Kelleher NL. Journal of Proteome Research. 2014 July 3;13(7):3231-3240.
Cell-free Protein Synthesis from a Release Factor 1 Deficient Escherichia coli Activates Efficient and Multiple Site-specific Nonstandard Amino Acid Incorporation. Hong SH, Ntai I, Haimovich AD, Kelleher NL, Isaacs FJ, and Jewett MC. ACS Synthetic Biology. 2014 June 20;3(6):398-409.
Applying Label-Free Quantitation to Top Down Proteomics. Ntai I, Kim K, Fellers RT, Skinner OS, Smith AD, Early BP, Savaryn JP, LeDuc RD, Thomas PM, and Kelleher NL. Analytical Chemistry. 2014 May 20;86(10):4961-4968.
The first pilot project of the consortium for top-down proteomics: A status report. Dang X, Scotcher J, Wu S, Chu RK, Tolic N, Ntai I, Thomas PM, Fellers RT, Early BP, Zheng Y, Durbin KR, LeDuc RD, Wolff JJ, Thompson CJ, Pan J, Han J, Shaw JB, Salisbury JP, Easterling M, Borchers CH, Brodbelt JS, Agar JN, Pasa-Tolic L, Kelleher NL, and Young NL. Proteomics. 2014 May;14(10):1130-1140.
Autopilot: An Online Data Acquisition Control System for the Enhanced High-Throughput Characterization of Intact Proteins. Durbin KR, Fellers RT, Ntai I, Kelleher NL, and Compton PD. Analytical Chemistry. 2014 February 4;86(3):1485-1492.
Strain-specific proteogenomics accelerates the discovery of natural products via their biosynthetic pathways. Albright JC, Goering AW, Doroghazi JR, Metcalf WW, and Kelleher NL. Journal of Industrial Microbiology & Biotechnology. 2014 February;41(2):451-459.
Large-scale Top-down Proteomics of the Human Proteome: Membrane Proteins, Mitochondria, and Senescence. Catherman AD, Durbin KR, Ahlf DR, Early BP, Fellers RT, Tran JC, Thomas PM, and Kelleher NL. Molecular & Cellular Proteomics. 2013 December 1;12(12):3465-3473.
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.
View all publications by Neil L. Kelleher listed in the National Library of Medicine (PubMed). Current and former IBiS students in blue.