Lingjun Li
PhD, University of Illinois at Urbana-Champaign
Assistant Professor Pharmacy and Chemistry

Contact Information:
5125 Rennebohm
777 Highland Ave.
Madison, WI 53705-2222
Phone: (608) 265-8491
E-mail: lli@pharmacy.wisc.edu
Web: Pharmacy
Web: Lab

Research Statement

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. 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 have developed several unique sample preparation strategies and instrumentation protocols that enable sensitive analysis of neuropeptides directly from minute quantities of neural tissues. By combining chemical labeling, micro-scale separation, and tandem mass spectrometry sequencing techniques, we have discovered a large number of novel neuropeptides used in crustacean nervous systems. The physiological effects of these new peptides at the cellular and network levels are evaluated in collaboration with laboratories of Eve Marder and Michael Nusbaum. Furthermore, both mass spectrometric imaging techniques 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 mammalian systems. These collaborative projects include the discovery of prion disease biomarkers in cerebral spinal fluids and serum (in collaboration with Judd Aiken and David Page), proteomic analysis neuroprotective factors secreted by astrocytes (in collaboration with Jeff Johnson), and proteomic study of dioxin-induced cardiotoxicity in developing zebrafish (in collaboration with Warren Heideman and Dick Peterson). We are also interested in developing new collaborations with other investigators at the Waisman Center to help transform advances in analytical tools into important findings that lead to new diagnosis and therapeutic strategies.

Representative Publications

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.

Q. Fu, L. Tang, E. Marder, and L. Li (2007). Mass spectrometric characterization and physiological actions of VPNDWAHFRGSWamide, a novel B-type allatostatin in Cancer crabs. Journal of Neurochemistry 101, 1099-1107.

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.

S.R. Saideman, M. Ma, K. K. Kutz-Naber, A. Cook, P. Torfs, L. Schoofs, L. Li, and M. P. Nusbaum (2007). Modulation of rhythmic motor activity by pyrokinin peptides. Journal of Neurophysiology 97, 579-595.

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. DeKeyser and L. Li (2007). Mass spectrometric charting of neuropeptides in arthropod neurons. Analytical and Bioanalytical Chemistry 387, 29-35.

S. DeKeyser and L. Li (2006). Matrix-assisted laser desorption/ionization Fourier transform mass spectrometry (MALDI FTMS) quantitation via in-cell combination (QUICC). Analyst. Invited contribution to the special issue of Emerging Investigators. 131, 281-290.

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, K. K. Kutz, J. J. Schmidt, Y-W.A. Hsu, S. D. Cain, J. M. Edwards, L. V. Ambroggio, T. G. Halatchev, A. E. Christie, and L. Li (2005). Hormone complement of the Cancer productus sinus gland and pericardial organ: an anatomical and mass spectrometric investigation. Journal of Comparative Neurology 493, 607-626.

Click here to search National Library of Medicine and PubMed for other publications by Dr. Li.

Awards & Honors