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Pharmaceutical Sciences Division

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Lingjun Li, Ph.D.

Professor

5125 Rennebohm Hall
Phone:608-265-8491
FAX: 608-262-5345
Email: lli@pharmacy.wisc.edu

Email Lingjun Li

Education:

  • B.E. 1992 Env. Analyt. Chem. - Beijing Polytechnic University
  • Ph.D. 2000 Analyt & Biomol Chem - University of Illinois at Urbana-Champaign (UIUC)
  • Postdoc 2002 Analyt Chem/NeuroSci - Pacific Northwest National Laboratory, Brandeis University, UIUC

Research:

Research in my laboratory focuses on developing and implementing an array of novel mass spectrometry based strategies to answer questions about the most complex and elusive set of signaling molecules, the neuropeptides, and gain new insights into the roles of peptide hormones and neurotransmitters play in the plasticity of neural circuits and behavior. While significant effort has been directed to analytical technique and method development, it is the biomedical importance of understanding the neuropeptidergic system that drives our research to continuously refine and improve the analytical capabilities to address challenging neuroscience problems. A large body of research strongly suggests that an imbalance of chemical messengers is associated with various neurological disorders. However, compared to classical neurotransmitters such as amines, the functional roles of many neuropeptides are still poorly understood. This is, in part, due to the lack of analytical capabilities to measure and identify these low abundance endogenous signaling molecules in a complex microenvironment. Clearly, development of highly sensitive and selective analytical tools for neuropeptide identification and quantitation is in great demand. Specifically, we are interested in understanding the roles that neuropeptides play in food intake, neural network development and response to environmental stresses.

We have chosen to work with a simpler and well-defined crustacean nervous system to both facilitate technology development and address fundamental neuroscience problems related to neuromodulation and network plasticity. We are developing a multi-faceted mass spectrometry-based analytical platform to probe peptidergic signaling with enhanced sensitivity and selectivity. By combining chemical labeling, micro-scale separation (capillary electrophoresis and nanoLC), and tandem mass spectrometry sequencing techniques, we have discovered a large number of novel neuropeptides in crustacean nervous systems. The physiological effects of these new peptides at the cellular and network levels are evaluated in collaboration with neurophysiologists (Eve Marder and Michael Nusbaum) in the field. Furthermore, both mass spectrometric imaging technology and in vivo microdialysis sampling tools have been implemented to follow neuropeptide distribution and secretion with unprecedented details. Finally, a differential display strategy in conjunction with isotopic labeling technique is being developed to allow functional discovery of neuropeptides in response to various physiological changes.

While the technology is developed using crustacean model system as a test-bed, the technology advancement resulting from our research is widely applicable to the large-scale analysis of peptides and proteins in many biological systems, including those of mammalian and humans. Towards this end, we have established several exciting collaborations targeted at neurochemical analysis in more complex systems. These collaborative projects include biomarker discovery in neurodegenerative diseases (with Albee Messing and Judd Aiken), peptide analysis and neuromodulation in mammalian rhythmic neural network (with Jan Marino (Nino) Ramirez), proteomic analysis neuroprotective factors secreted by astrocytes (with Jeffrey Johnson), and proteomic study of dioxin-induced cardiotoxicity in developing zebrafish (with Warren Heideman and Richard Peterson).

These synergistic projects span analytical mass spectrometry, capillary separations, peptide chemistry, bioinformatics, neurochemistry, and neurobiology. The improved analytical method development enables biological discovery, and the emerging biological questions require further advancement of analytical tools.

Li Lab Research Overview

Bio:

Background: Lingjun received her B.E. degree in Environmental Analytical Chemistry from Beijing Polytechnic University and a Ph.D. degree in Analytical Chemistry/Biomolecular Chemistry from University of Illinois at Urbana-Champaign. She did three-way postdoctoral research at the Pacific Northwest National Laboratory, Brandeis University, and University of Illinois before joining the School of Pharmacy faculty in 2002. She currently holds joint appointments in School of Pharmacy and Department of Chemistry at UW-Madison. Her research interests are in analytical neurochemistry, neuroproteomics and biological mass spectrometry.

Professional Interests: Drug Action and Drug Discovery

Highlighted Publications:

  • R. Chen, L. Hui, R. Sturm, and L. Li (2009). Three dimensional mapping of neuropeptides and lipids in crustacean brain by mass spectral imaging. Journal of American Society for Mass Spectrometry, doi:10.1016/j.jasms.2009.01.017.
  • M. Ma, R. Chen, Y. Ge, H. He, A.G. Marshall, and L. Li (2009). Combining bottom-up and top-down mass spectrometric strategies for de novo sequencing of the crustacean hyperglycemic hormone (CHH) from Cancer borealis. Analytical Chemistry, 81, 240-247.
  • A. Herbst, S. McIlwain, J. J. Schmidt, J. M. Aiken, C. D. Page, and L. Li (2009). Prion disease diagnosis by proteomic profiling. Journal of Proteome Research, DOI: 10.1021/pr800832s.
  • R. Chen, M. Ma, L. Hui, J. Zhang, and L. Li (2009). Measurement of neuropeptides in crustacean hemolymph via MALDI mass spectrometry. Journal of the American Society for Mass Spectrometry Published on-line on Dec 24, 2008, doi:10.1016/j.jasms.2008.12.007
  • X. Wei and L. Li (2009). Comparative glycoproteomics: approaches and applications. Briefings in Functional Genomics and Proteomics [Published on-line Dec 17, 2008, doi:10.1093/bfgp/eln053].
  • J. A. Dowell, D. C. Frost, J. Zhang, and L. Li (2008). Comparison of two-dimensional fractionation techniques for shotgun proteomics. Analytical Chemistry, 80, 6715-6723.
  • H. Behrens, R. Chen, and L. Li. Combining microdialysis, nanoLC-MS, and MALDI-TOF/TOF to monitor neuropeptide secretion in the crab, Cancer borealis. Analytical Chemistry, 80, 6949-6958.
  • J. Wang, M. Ma, R. Chen, and L. Li (2008). Enhanced neuropeptide profiling via capillary electrophoresis off-line coupled with MALDI FTMS. Analytical Chemistry, 80, 6168-6177.
  • L. Li and J.V. Sweedler (2008). Peptides in our brain: measurement approaches and challenges. Inaugural volume of Annual Review of Analytical Chemistry. 1, 451-483.
  • S.S. Cape, K. J. Rehm, M. Ma, E. Marder, and L. Li (2008). Mass spectral comparison of the neuropeptide complement of the stomatogastric ganglion and brain in the adult and embryonic lobster, Homarus americanus. Journal of Neurochemistry 105, 690-702.
  • J.J. Schmidt, S. S. McIlwain, D. Page, A. E. Christie, and L. Li (2008). Combining MALDI-FTMS and bioinformatics for rapid peptidomic comparisons. Journal of Proteome Research. 7, 887-896.
  • J. Wang, R. Chen, M. Ma, and L. Li (2008). MALDI MS sample preparation by using paraffin wax film: systematic study and application for peptide analysis. Analytical Chemistry 80, 491-500.
  • S.S. DeKeyser, K. K. Kutz-Naber, J. J. Schmidt, G.A. Barrett-Wilt, and L. Li (2007) Mass spectral imaging of neuropeptides in crustacean nervous tissue by MALDI TOF/TOF. Journal of Proteome Research 6, 1782-1791.
  • M. Ma, K, K. Kutz-Naber, and L. Li (2007). Methyl esterification assisted MALDI FTMS characterization of orcokinin neuropeptide family. Analytical Chemistry 79, 673-681.
  • S. S. DeKeyser and L. Li (2007). Mass spectrometric charting of neuropeptides in arthropod neurons. Analytical and Bioanalytical Chemistry 387, 29-35.
  • J. A. Dowell, W. Vander Heyden, and L. Li (2006). Rat neuropeptidomics by LC/MS/MS and MALDI-FTMS: enhanced dissection and extraction techniques coupled with 2D RP-RP HPLC separation. Journal of Proteome Research 5, 3368-3375.
  • S. DeKeyser and L. Li (2006). Matrix-assisted laser desorption/ionization Fourier transform mass spectrometry (MALDI FTMS) quantitation via in-cell combination (QUICC). Analyst 131, 281-290.
  • C. Zhang, B.R. Griffth, Q. Fu, X. Fu, C. Albermann, I.K. Lee, L. Li, and J.S. Thorson (2006). Exploiting the indiscriminate and reversible nature of the Calicheamicin Rhamnosyltransferase CalG1 for enediyne glycorandomization. Science 313, 1291-1294.
  • Q. Fu and L. Li (2006). Fragmentation of peptides with N-terminal dimethylation and imine/methylol adduction at tryptophan side chain. J. Am. Soc. Mass Spectrom. 17, 859-866.
  • Q. Fu and L. Li (2005). De novo sequencing of neuropeptides using reductive isotopic methylation and investigation of ESI QTOF MS/MS fragmentation pattern of neuropeptides with N-terminal dimethylation. Analytical Chemistry 77, 7783-7795.
  • Q. Fu, M. Goy, and L. Li (2005). Identification of neuropeptides from the sinus gland of the Jonah crab, Cancer borealis and the Maine lobster, Homarus americanus using nanoscale liquid chromatography tandem mass spectrometry. Biochem. Biophys. Res. Commun. 337, 765-778.
  • K. K. Kutz, J. J. Schmidt, and L. Li (2004). In situ tissue analysis of neuropeptides by MALDI FTMS in-cell accumulation. Analytical Chemistry 76, 5630-5640.