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

Research Interests

Our laboratory’s research  focuses  on the areas of top-down proteomics, natural products discovery, and proteoform biology,  driving  both technology development and applications of high-performance  mass spectrometry  in proteomics and microbial natural products. More specifically, our main interests lie in the enzymology of natural product biosynthesis, development of Fourier Transform Mass Spectrometry (FTMS) technologies for Top Down Proteomics (i.e. analyzing intact proteins directly; no proteases), and translational studies of proteoforms across 4 disease-focused subgroups: cardioproteomics, oncoproteomics, neuroproteomics, and immunoproteomics.

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

Correlative metabologenomics of 110 fungi reveals metabolite–gene cluster pairs. Caesar LK, Butun FA, Robey MT, Ayon NJ, Gupta R, Dainko D, Bok JW, Nickles G, Stankey RJ, Johnson D, Mead D, Cank KB, Earp CE, Raja HA, Oberlies NH, Keller NP, and Kelleher NL. Nature Chemical Biology. 2023 July;19(7):846-854.

Mapping the KRAS proteoform landscape in colorectal cancer identifies truncated KRAS4B that decreases MAPK signaling. Adams LM, DeHart CJ, Drown BS, Anderson LC, Bocik W, Boja ES, Hiltke TM, Hendrickson CL, Rodriguez H, Caldwell M, Vafabakhsh R, and Kelleher NL. Journal of Biological Chemistry. 2023 January;299(1):102768.

Divergent Antibody Repertoires Found for Omicron versus Wuhan SARS-CoV-2 Strains Using Ig-MS. Forte E, Des Soye BJ, Melani RD, Hollas MAR, Kafader JO, Sha BE, Schneider JR, and Kelleher NL. Journal of Proteome Research. 2022 December 2;21(12):2987-2997.

Highly multiplexed, label-free proteoform imaging of tissues by individual ion mass spectrometry. Su P, McGee JP, Durbin KR, Hollas MAR, Yang M, Neumann EK, Allen JL, Drown BS, Butun FA, Greer JB, Early BP, Fellers RT, Spraggins JM, Laskin J, Camarillo JM, Kafader JO, and Kelleher NL. Science Advances. 2022 August 12;8(32):eabp9929.

The Blood Proteoform Atlas: A reference map of proteoforms in human hematopoietic cells. Melani RD, Gerbasi VR, Anderson LC, Sikora JW, Toby TK, Hutton JE, Butcher DS, Negrão F, Seckler HS, Srzentic K, Fornelli L, Camarillo JM, Leduc RD, Cesnik AJ, Lundberg E, Greer JB, Fellers RT, Robey MT, DeHart CJ, Forte E, Hendrickson CL, Abbatiello SE, Thomas PM, Kokaji AI, Levitsky J, and Kelleher NL. Science. 2022 January 28;375(6579):411-418. 

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