Neil L. Kelleher Top-down proteomics, natural products discovery, chromatic oncobiology, & computational proteomics

Research Interests

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.

Selected Publications

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.

View all publications by Neil L. Kelleher listed in the National Library of Medicine (PubMed). Current and former IBiS students in blue.