Comprehensive characterization of all signaling molecules in a nervous system with chemical, spatial and temporal information is often critical to deciphering the functionality of a neural circuit yet it presents a daunting challenge. In this presentation, I will present our recent progress on the development of a multi-faceted MS-based analytical platform to probe neuronal signaling with enhanced sensitivity and selectivity. By combining chemical labeling, micro-scale separation, and tandem MS sequencing techniques, we discovered more than 300 novel neuropeptides in crustacean nervous systems. The novel utility of ion mobility spectrometry for enhanced peptide identification and characterization will be highlighted. More recently, we expanded our research efforts to biomarker discovery in several neurological disorders including autism and Alzheimer’s disease. Using a combination of matrix-assisted laser desorption/ionization (MALDI) mass spectrometric imaging (MSI) and top-down proteomics, the utility of MALDI-MSI as a discovery tool for potential biomarkers is highlighted. Furthermore, endogenous peptidome of the cerebrospinal fluid samples were also examined for the first time to reveal potential AD biomarkers. Finally, novel dimethylated leucine (DiLeu) isobaric tagging reagents have been developed and evaluated for their utility in large-scale multiplexed quantitative proteomics. Several on-going efforts and future perspectives provided by these enabling technologies will be discussed. https://pharmacy.wisc.edu/li-lab/
Bio: Dr. Lingjun Li is a Vilas Distinguished Achievement Professor and the Janis Apinis Professor of Pharmaceutical Sciences and Chemistry at the University of Wisconsin-Madison. Dr. Li received her B.E. degree in Environmental Analytical Chemistry from Beijing University of Technology, China and her Ph.D. degree in Analytical Chemistry/Biomolecular Chemistry from the University of Illinois at Urbana-Champaign under Jonathan Sweedler in 2000. She then did joint postdoctoral research at the Pacific Northwest National Laboratory (w/ Richard Smith) and Brandeis University (w/ Eve Marder) before joining the faculty at UW-Madison in December 2002. Dr. Li’s research interests include the development of novel mass spectrometry (MS)-based tools such as new isotopic and isobaric labeling strategies that enable hyperplexing for quantitative proteomics, microscale separations, in vivo microdialysis and imaging MS for functional discovery of neuropeptides and protein biomarkers in neurodegenerative diseases. Her lab also explores novel use of ion mobility MS to address technical challenges in peptidomic research, including site-specific peptide epimer analysis and improvement of isobaric tandem MS quantitation. Professor Li has established a highly productive research program and published more than 190 peer-reviewed research journal papers. She has given more than 170 invited talks. She has been recognized with numerous awards, including ASMS Research Award, NSF CAREER Award, Sloan Fellowship, PittCon Achievement Award, and 2014 ASMS Biemann Medal, and was named one of the Top 50 most influential women in the analytical sciences and was included in the 2016 Analytical Scientist Power List. Dr. Li served as an Associate Editor for Analytical Methods during 2013-2016. She is currently serving as an Associate Editor for the Journal of The American Society for Mass Spectrometry (JASMS). Dr. Li has served on the ASMS Education Committee, Asilomar Conference Committee, the US HUPO Board of Directors, and is currently the President for the Chinese American Society for Mass Spectrometry (CASMS).