DEPARTMENT OF CHEMISTRY

Affiliations

BMBCB and Feinberg School of Medicine

Director, Chemistry of Life Processes Institute (CLP)

Walter and Mary Elizabeth Glass Professor in the Life Sciences

Director, Northwestern Proteomics

Department of Molecular Biosciences

Feinberg School of Medicine

Research Statement

The Kelleher Group is comprised of three main sub-groups: Top Down Proteomics, Natural Products Biosynthesis/Discovery, and Chromatin Biology and is recognized as a significant force in each of these three areas. We have been successful in driving both technology development and applications of high performance mass spectrometry at the interface of chemistry and biology. Over the last decade, we have generated ~120 publications, ~50 Ph.D. students/postdoctoral trainees, and ProSight software via the web to over 650 labs worldwide. The core of the Kelleher Team is built around expertise in complex mixture analysis using Fourier-Transform Mass Spectrometry for targeted applications in proteomics and natural products research. More specifically, we pursue the biosynthesis and discovery of polyketides and non-ribosomally produced peptides from soil bacteria and are leading the way to use intact proteins directly (no proteases like trypsin) as the primary unit of measurement in proteomics to efficiently detect their post-translational modifications.

Selected 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.

Selected Honors/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