Barry L. Karger
 

Director, 
James L. Waters Chair 
in Analytical Chemistry


The Barnett Institute, 341 Mugar
Northeastern University
360 Huntington Avenue
Boston MA 02115
email: b.karger@neu.edu
voice: 617-373-2867
fax: 617-373-2855
Karger Research Group Page

  
 

Education
 
1960 B.S., Chemistry, MIT
  1963 Ph.D. Chemistry, Cornell University
 
Research Interests
 

 

 

 

 
  1. Trace Level Comprehensive Characterization of Complex Proteins
    1. Use of large peptide fragment analysis for high sequence coverage of phosphorylated, glycosylated and other post-translationally modified structures. 
    2. Analysis of kinetics of phosphorylation upon stimulation by extra-cellular signals of tyrosine kinase receptors.
    3. Determination of binding partners of receptors upon stimulation by extra-cellular signals, e.g. drugs, after immunoprecipitation.
  1. Analysis of Complex Proteins Using a Combination of Collision Induced Dissociation (CID) and Electron Transfer Dissociation (ETD). 
    1. Trace level analysis of phosphorylated proteins using CID and ETD
    2. Glycosylation analysis using CID for structure and ETD for site localization
    3. Studies of fragmentation of charge reduced species
  1. Ultra-Trace Analysis of Proteomic Samples Using Very Narrow Bore LC Columns
    1. Monolithic packed columns of polystyrene divinylbenzene with 20 micron i.d..
    2. Ultra-trace analysis using 10 micron and lower porous layer open tubular (PLOT) columns
    3. Development of miniaturized on-line sample processing and analysis by LC/MS.
  1. Differential Quantitative Analysis of Laser Capture Micro-Dissection (LCM) Samples from Breast Cancer Tumors and Dysplastic Cells from Cervical Cancer.
    1. Trace analysis of LCM samples from breast cancer patients
    2. Discovery of biomarkers for dysplastic cells from cervical tracings as a means of improved diagnosis of pap smears.
    3. Analysis of paraffin embedded formalin fixed tissue.
  1. Proteomic Analysis of Microorganisms
    1. Discovery of energy conserved pathways of anaerobic bacteria (archaea) under carbon monoxide atmosphere – earliest form of life on earth.
    2. Pathway analysis of methane producing anaerobic bacteria as an alternative source of energy
    3. Use of proteomic analysis to enhance fermentation growth of microorganisms.
  1. Discovery and Implementation of Monoclonal Antibodies as Specific Reagents for Biomarker Analysis for Use in Clinical Diagnosis
    1. Discovery and generation of monoclonal antibodies to low-level disease specific markers in plasma.
    2. Implementation of protein microarray monoclonal antibodies for diagnostic analysis.
    3. Elucidation of clinical relevance of discovery of disease specific biomarkers.
  1. Implantable Devices for Monitoring of Biomarkers in Blood and Tissue
    1. Development of antibody coated nanoparticles for diagnostic purposes
    2. In collaboration with the Center for Nanomanufacturing at Northeastern, implementation of a nanodevice with antibody coated nanoparticles for implementation in the blood stream of mice.
    3. Determination of biomarker changes upon administration of drugs to mice.
    4. Ultimately develop implantable devices in humans for monitoring various physiological levels of the body.
  1. Development of Bioinformatic Tools for Proteomic Analysis
    1. Algorithms for quantitative analysis of label-free and isotopically labeled samples
    2. Novel tools for selection and annotation of CID spectra of glycopeptides
    3. De novo peptide sequencing and identification of PTMs
    4. Integration of proteomic data with metabolic and regulatory pathways
  1. New Methodologies for Proteomic Analysis
    1. Proteomic analysis of organisms with unsequenced genomes
    2. Identification of metabolic bottlenecks in the production of important valuable anti-cancer compounds in plant cell cultures
 
Awards (Partial Listing)
           
  (1)   American Chemical Society Award in Chromatography, sponsored by Supelco, Inc., Las Vegas, Nevada, 1982;
           
  (2)   American Chemical Society Award in Analytical Chemistry sponsored by the Fisher Scientific Company, 1990;
           
  (3)   1998 ACS Award in Separations Science and Technology sponsored by IBC Advanced Technologies, Inc. and Millipore Corporation, 15th ACS National Meeting, Dallas, TX, 1998;
           
  (4)   2002 Halasz Medal of the Hungarian Chemical Society for Chromatography and Separation Science;
         

 
  (5)   2003 CaSSS Award for Distinguished Contributions to Separation Science, San Francisco, CA, 2003;
           
  (6)   2004 Michael Widmer Award, sponsored by the New Swiss Chemical Society and Novartis, Salzburg, Austria 2004.


Select Recent Publications   (Complete List) 
  • Csanky, E., Olivova, P., Rajnavolgyi, E., Hempel, W., Tardieu, N., Katalin, E.T., Jullien, A., Malderez-Bloes, C., Kuras, M., Duval, M.X., Nagy, L., Scholtz, B., Hancock, W.S., Karger, B.L., Guttman, A., Takacs, L., "Monoclonal Antibody Proteomics: Discovery and Prevalidation of Chronic Obstructive Pulmonary Disease Biomarkers in a Single Step", Electrophoresis, 28, #23, 4401-4406, (2007). pubmed
  • Gu, Y., Wu, S-L., Meyer, J.L., Hancock, W.S., Burg, L.J., Linder, J, Hanlon, D.W., and Karger B.L.   "Proteomic analysis of high-grade dysplastic cervical cells obtained from ThinPrep slides using laser capture microdissection and mass spectrometry."  J. Proteome Res. 6(11):4256-68, (2007). pubmed 
  • Wu, S-L., Hühmer, A.F., Hao, Z., and Karger, B.L. "On-line LC-MS approach combining collision-induced dissociation (CID), electron-transfer dissociation (ETD), and CID of an isolated charge-reduced species for the trace-level characterization of proteins with post-translational modifications."  J. Proteome Res. 6(11):4230-44, (2007). pubmed 
  • Zvonok, N., Yaddanapudi, S., Williams, J., Dai, S., Dong, K., Rejtar, T., Karger, B.L. and Makriyannis, A., " Comprehensive Proteomic Mass Spectrometric Chracterization of Human Cannabinoid CB2 Receptor", J. Proteome Research, 2068-2079, (2007).pubmed 
  • Zhang, J., Wu, S., Kim, J. and Karger, B.L., "Ultratrace liquid chromatography/mass spectrometry analysis of large peptides with post-translational modifications using narrow-bore poly(styrene- divinylbenzene) monolithic columns and extended range proteomic analysis", J. Chromatogr A., 1154, 295-307, (2007).pubmed 

  • Luo, Q., Yue, G., Valaskovic, G., Gu, Y., Wu., S-L. and Karger, B.L. "On-Line 1D and 2D PLOT/LC-ESI-MS Using 10 µm i.d. Poly(styrene-divinylbenzene) Porous Layer Open Tubular (PLOT) columns for Ultrasensitive Proteomic Analysis", Anal. Chem., 79(16):6174-81 (2007).pubmed 

  • Ren, J. M., Rejtar, T., Li, L. and Karger, B. L. "Automated N-Glycan Structure Annotation of Glycopeptides Using a Linearized Structure database (GlyDB)", J. of Proteome Research, accepted, (2007).pubmed 

  • Andreev, V., Li, L., Cao, L., Gu, Y., Rejtar, T., Wu, S-L. And Karger, B.L. "A New Algorithm Using Cross-Assignment for Label-Free Quantitation with LC/LTQ-FT MS", J. of Proteome Res., 6, 2186-2194, (2007). pubmed

  • Li, L., Li, Q., Rohlin, L., Kim, U., Salmon, K., Rejtar, T., Gunsalus, R.P., Karger, B.L. and Ferry, J.G. "Quantitative proteomic and microarray analysis of the archaeon Methanosarcina acetivorans grown with acetate versus methanol", J. of Proteome Res, 6, 759-771, (2007). pubmed

  • Yue G, Luo Q, Zhang J, Wu SL, Karger BL. "Ultratrace LC/MS proteomic analysis using 10-µm-i.d. Porous layer open tubular poly(styrene-divinylbenzene) (PLOT) capillary columns."  Anal Chem.  79(3):938-46, Feb 1 2007;  pubmed
  • Lessner, D., Li, L., Li, Q., Rejtar, T., Andreev, A., Reichlen, M., Hill, K., Moran, J., Karger, B.L. and Ferry, J. G. "An Unconventional Pathway for Reduction of CO2 to Methane in CO-grown Methanosarcina Acetivorans Revealed by Proteomics" PNAS (103) 17921, (2006). pubmed

  • Correia, F., D'Onofrio, A., Rejtar,T., Li, L., Karger, B.L., Makarova, K., Koonin, E.V., and Lewis, K., "Kinase Activity of Overexpressed HipA is Required for Growth Arrest and Multidrug Tolerance in Escherichia coli", J. of Bacteriology, vol. 188 (24) 8360-8367, (2006).pubmed 

  • Wu, S.L., Kim, J., Bandle, R., Liotta, L., Petricoin, E. And Karger, B.L., "Dynamic profiling of the post-translational modifications and interaction partners of epidermal growth factor receptor signaling after stimulation by EGF using extended range proteomic analysis (ERPA)", Mol. Cell,. 5, 1610-1627, 2006. pubmed 
  • Andreev, V., Li, L., Cao, L., Gu, Y., Kim, J., Rejtar, T., Wu, S. And Karger, B.L., "A New Algorithm for 15N/14N Quantitation with LC-ESI-MS Using an LTQ-FT Mass Spectrometer", J. of Proteome Res, 5; 2039-2045, 2006. pubmed 

  • Moskovets,E., Preisler, J., Chen, H.S., Rejtar, T., Andreev, V. and Karger. B.L., "High-Throughput Axial MALDI-TOF MS Using a 2 kHz Repetition Rate Laser", Anal. Chem., 78, 912-919 (2006). pubmed

  • Li, Q., Li, L., Rejtar, T., Lessner, D., Karger, B.L. and Ferry, J.G., "Electron Transport in the Pathway of Acetate Conversion to Methane in the Marine Archaeon Methanosarcina acetivorans", J. of Bacteriol., 188(2), 702-710, (2006).pubmed
  • Karger, Barry L. "Shigeru Terabe, a Colleague and Outstanding Scientist", J. of Chrom, A., 3, 1106 (2006).

  • Chen, H., Rejtar, T., Andreev, V., Moskovets, E. and Karger, B.L., "A New Strategy for Enhanced Characterization of Complex Proteomic Samples Using LC-MALDI MS/MS: Exclusion of Redundant Peptides from MS/MS Analysis in Replicate Runs" Anal. Chem, 77, 7816 -7825 (2005).
  • Wu, S., Kim, J., Hancock, W.S., Karger, B.L., "Extended Range Proteomic Analysis (ERPA): New and Sensitive LC-MS Platform for High Seqeucne Coverage of Complex Proteins with Extensive Posttranslational Modifications -Comprehensive Analysis of Beta-Casein and Epidermal Growth Factor Receptor", J. of Proteome Res., 4(4); 1155-1170 (2005).

  • Li-Sucholeiki, X., Tomita-Mitchell, A., Arnold, K., Glassner, B., Thompson, T., Murthy, J., Berk, L., Lange, C., Leong-Morgenthaler, P., MacDougall, D., Munro, J., Cannon, D., Mistry, T., Miller, A., Deka, C., Karger, B.L., Gillespie, K., Ekstrom, P., Todd, J. and Thilly, W. " Detection and Frequency Estimation of Rare Variants in Pools of Genomic DNA from Large Populations Using Mutational Spectrometry", Mutation Research, 570, 267-280 (2005).
  • Li, Q., Deka, C., Glassner, B., Arnold, K., Li-Sucholeiki, X., Tomita-Mitchell, A., Thilly, W. and Karger, B.L., "Design of an Automated Instrument with Fraction Collection for DNA Mutation Discovery by Constant Denaturant Capillary Electrophoresis (CDCE)." J. of Separation Science, 28 1375-1389 (2005).
  • Chen, H., Rejtar, T., Andreev, V., Moskovets, E. and Karger, B.L. "High Speed - High Resolution Monolithic Capillary LC-MALDI MS Using an Off-line Continuous Deposition Interface for Proteomic Analysis", Anal. Chem., 77, 2323-2331 (2005).

  • Pashkova, A., Chen, H., Rejtar, T., Zang, X., Giese, R., Andreev, V., Moskovets, E. Karger, Barry L. "Coumarin Tags for Improved Analysis of Peptides by MALDI-TOF MS and MS/MS. II. Alexa Fluor 350 Tag for Increased Peptide and Protein Identification by LC-MALDI-TOF/TOF MS", Anal. Chem., .77(7); 2085-2096, (2005).
  • Li , Q, Li, L, Rejtar, T, Karger, B.L. and Ferry, J. "The Proteome of Methanosarcina acetivorans. Part II, Comparison of Protein Abundance in Acetate- and Methanol-Grown Cells", J. of Proteome Res., 4(1); 129-135. (2005)
  • Li , Q, Li, L, Rejtar, T, Karger, B.L. and Ferry, J. "The Proteome of Methanosarcina acetivorans. Part I, An Expanded View of the Biology of the Cell", J. of Proteome Res., 4(1), 112-128 (2005).

  • Kautz, R., Goetzinger, W. and Karger, B.L. "High Throughput Microcoil NMR of Compound Libraries Using Zero-Dispersion Segmented Flow Analysis." The Journal of Combinatorial Chemistry, 7(1); 14-20 (2005).

  • Wu, S., Jardine, I., Hancock, W.I. and Karger, B.L. "A New and Sensitive On-Line LC-MS Approach for Top-Down Protein Analysis: The Comprehensive Analysis of Human Growth Hormone in an E. coli Lysate Using a Hybrid Linear Ion Trap Fourier Transform Ion Cyclotron Resonance (FTICR) Mass Spectrometer", Rapid Comm. Mass Spec., 19, 2201-2207 (2004).

  • Rejtar, T., Chen, H., Andreev, V., Moskovets, E., and Karger, B.L. "Increased Identification by Peptides by Enhanced Data Processing of High Resolution MALDI TOF/TOF Mass Spectra Prior to Database Searching", Anal. Chem., 76, 6017-6028 (2004).

  • Pashkova, A., Moskovets, E. Karger, Barry L. "Coumarin Tags for Improved Analysis of Peptides by MALDI-TOF MS and MS/MS I. Enhancement in MALDI MS Signal ntensities", Anal. Chem., 76, 4550-4557 (2004).

  • Zang, L., Palmer-Toy, D., Hancock, W.S., Sgroi, D. and Karger, B.L. "Proteomic Analysis of Ductal Carcinoma of the Breast Using Laser Capture Microdissection, LC-MS and 16O/18O Isotopic Labeling", J. Proteome Res.,3, 604-612 (2004).

  • Paba, J.; Ricart, C. A. O.; Fontes, W.; Santana, J. M.; Teixeira, A. R. L.; Marchese, J.; Williamson, B.; Hunt, T.; Karger, B. L. Sousa, M. V., "Proteomic Analysis of Trypanosoma cruzi Developmental Stages Using Isotope-Coded Affinity Tag Reagents", J. Proteome Res., 3, 517-524, (2004).

  • Lazar, I.M., Horvath,C., Yang, Y., Karger, B.L."Microfluidic Device for Capillary Electrochromatography-Mass Spectrometry", Electrophoresis, 24, 3655-3662, (2003).

  • Moskovets, E., Chen, H., Pashkova, A., Rejtar, T., Andreev, V.P., Karger, B.L. "Closely Spaced External Standards: A Universal Method of Achieving 5 ppm Mass Accuracy Over the Entire MALDI Plate in MALDI-TOF MS", Rapid Commun. in Mass Spect., 17, 2177-2187, (2003).

  • Andreev, V.P., Rejtar, T., Moskovets, E., Ivanov, A., Karger, B.L."A Universal Denoising and Peak Picking Algorithm for LC-MS Based on Matched Filtration in the Chromatographic Time Domain", Anal. Chem., 75(22), 6314-6326 (2003).

  • Ivanov, A., Zang, L., Karger, B.L."Low Attomole ESI-MS and MS/MS Analysis of Protein Digests Using 20-µm I.D. Polystyrene-Divinylbenzene Monolithic Capillary Columns", Anal. Chem., 75(20), 5306-5316 (2003).

  • Ivanov, A., Horvath, C., Karger, B.L."High-Efficiency Peptide Analysis on Monolithic Multi-Mode Capillary Columns: Pressure Assisted CEC/CE Coupled to UV and ESI-MS", Electrophoresis, 24, 3663-3673, (2003).

  • Guttman, A., Karger, B.L., "Capillary Electrophoresis and the Human Genome Project", Genomic/Proteomic Tech., 3, #3, 12-20, April/May (2003).

  • Moskovets Eugene, Karger, B.L."Mass Calibration of MALDI-TOF MS Including Rise Time of the Delayed Extraction Pulse", Rapid Commun. in Mass Spec., 17, 229-237 (2003).
 

 

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