Understanding the full puzzle of proteins: A chemistry engineer works to improve a flawed test for a common cancer

Top-down proteomics approach gets to the bottom of cancer

Neil L. Kelleher, PhD

Walter and Mary Glass Professor of Molecular Biosciences and Professor of Chemistry, Weinberg College of Arts and Sciences
Professor of Medicine, Feinberg School of Medicine

Member, Chemistry of Life Processes Institute
Faculty Director, Northwestern Proteomics, Chemistry of Life Processes Institute

Neil L. Kelleher, PhD, is the Walter and Mary E. Glass Professor of Molecular Biosciences and professor of chemistry in the Weinberg College of Arts and Sciences. He is also a professor of medicine in the Feinberg School of Medicine. His primary research interests include top down proteomics, natural products discovery, and cancer biology. Kelleher is faculty director of Northwestern Proteomics, a member of the Chemistry of Life Processes Institute and the Robert H. Lurie Comprehensive Cancer Center.

Neil Kelleher’s research group is focused on top-down proteomics, chromatin biology, and natural product biosynthesis and discovery. Contributing to both technology development and application of mass spectrometry in chemistry and biology, The Kelleher Research Group is interested in the biosynthesis and discovery of novel natural products with potential pharmacological activities. The lab is leveraging top-down proteomics — the analysis of intact proteins for precise localization of post-translational modifications — to advance and contribute to the understanding of chromatin and cancer biology.  Kelleher is both a pioneer and champion of the top-down approach.

Kelleher received a B.S. and B.A. from Pacific Lutheran University in 1992, a Fulbright Fellowship the following year, and a Ph.D. from Cornell University in 1997 completing his joint graduate work with Tadhg Begley and Fred McLafferty.  In 1999, after a NIH Postdoctoral Fellowship at Harvard Medical School with Chris Walsh, Kelleher joined the faculty at University of Illinois at Urbana-Champaign where he established his research program in proteomics. In 2010, he joined the faculty at Northwestern University.

Kelleher is the recipient of many honors, including the Arthur P. Sloan Foundation Fellowship, Packard Fellowship, Dreyfus Award for New Investigators, Camille Dreyfus Teacher-Scholar Award, Lilly Analytical Chemistry Award, and NIH Career Transition Award. He was also a Burroughs Wellcome Fund Young Investigator and a Searle Scholar. In 2004, he received the Presidential Early Career Award for Scientists and Engineers, the nation’s highest honor for professionals at the outset of their independent research careers.

Kelleher has written more than 300 publications. The ProSight software suite developed by Kelleher is used by more than 1,000 labs around the world.  He is the founder and president of the Consortium for Top Down Proteomics.

Publications

Durbin, K.R., Tran, J.C., Zamdborg, L., Sweet, S.M., Catherman, A.D., Lee, J.E., Li, M., Kellie, J.K., Kelleher, N.L. “Intact Mass Detection, Interpretation, and Visualization to Automate Top-Down Proteomics on a Large Scale” Proteomics [Epub ahead of print].

Kellie, J.F., Tran J.C., Lee, J.E., Ahlf, D.R., Thomas, H.M., Ntai, I., Catherman, A.D., Durbin, K.R., Zamdborg, L., Vellaichamy, A., Thomas, P.M., Kelleher, N.L. “The Emerging Process of Top Down Mass Spectrometry for Protein Analysis: Biomarkers, Protein-Therapeutics, and Achieving High Throughput” Mol. Biosyst., 2010, 6, 1532-1539.

Sweet, S.M., Li, M., Thomas, P.M., Durbin, K.R., Kelleher, N.L. “Kinetics of Re-establising H3 K79 Methylation Marks in Global Human Chromatin” J. Biol. Chem., 2010, epub ahead of print.

Evans, B.S., Robinson, S.J., Kelleher, N.L. “Surveys of Non-Robosomal Peptide and Polyketide Assembly Lines in Fungi and Prospects for Their Analysis in vitro and in vivo” Fungal Genet. Biol., 2010, epub ahead of print.

Zheng, Y., John S., Pesavento, J.J., Schultz-Norton, J.R., Schiltz, R.L., Baek, S., Nardulli, A.M., Hager, G.L., Kelleher, N.L., Mizzen, C.A. “Histone H1 Phosphorylation is Associated with Transcription by RNA Polymerase I and II” J. Cell Biol., 2010, 189, 407-415.

Romanova, E.V., Lee, J.E., Kelleher, N.L., Sweedler, J.V., Gulley, J.M. “Mass Spectrometry Screening Reveals Peptides Modulated Differentially in the Medial Prefrontal Cortex of Rats with Disparate Initial Sensitivity to Cocaine” AAPS Journal, 2010, 12, 443-454.

Johannes, T.W., Desieno, M.A., Griffin, B.M., Thomas, P.M., Kelleher, N.L., Metcalf, W.W., Zhao, H. “Deciphering the Late Biosynthetic Steps of Antimalarial Compound FR-900098” Chem. Biol., 2010, 17, 57-64.

Vellaichamy, A., Tran, J.C., Catherman, A.D., Lee, J.E., Kellie, J.F., Sweet, S.M., Zamdborg, L., Thomas, P.M., Ahlf, D.R., Durbin, K.R., Valaskovic, G.A., Kelleher, N.L. “Size-Sorting Combined with Improved Nanocapillary Liquid Chromatography-Mass Spectrometry for Identification of Intact Proteins up to 80 kDa” Anal. Chem., 2010, 82, 1234-1244.

Lee, J.E., Atkins, N. Jr., Hatcher, N.G., Zamdborg, L., Gillette, M.U., Sweedler, J.V., Kelleher, N.L. “Endogenous Peptide Discovery of the Rat Circadian Clock: A Focused Study of the Suprachiasmatic Nucleus by Ultrahigh Performance Tandem Mass Spectrometry” Mol. Cell. Proteomics, 2010, 9, 285-297.

Li, M., Jiang L., Kelleher, N.L. “Global Histone Profiling by LC–FTMS After Inhibition and Knockdown of Deacetylases in Human Cells” J. Chrom. B., 2009, 877, 3885-3892.

Select Honors and Awards

Biemann Medal (American Society for Mass Spectrometry), 2009
Pittsburgh Conference Achievement Award (American Chemical Society, DAC), 2008
Pfizer Award in Enzyme Chemistry (American Chemical Society, DBC), 2006
A.F. Findeis Award in Measurement Science (American Chemical Society, DAC), 2006
Presidential Early Career Award in Science and Engineering, 2005
Camille Dreyfus Teacher-Scholar Award, 2004
Sloan Fellow, 2003
Packard Fellowship, 2002-2007
Cottrell Scholars Award, 2002
National Science Foundation CAREER Award, 2002-2007
Research Corporation Innovation Award, 2001
Burroughs Wellcome Award in the Pharmacological Sciences, 2000-2003
Searle Scholar Award, 2000-2003
NIH (NIAID) K22 Career Transition Award, 2000-2002
American Society of Mass Spectrometry Research Award, 2000
Henry Dreyfus New Faculty Award, 1999-2000