Functional Neuropeptidomics: The imbalance of peptide hormones and neurotransmitters causes many neurological disorders. Our research interests focus on developing novel mass spectrometry (MS)-based methodologies to study these complex and elusive set of signaling molecules, and reveal the roles of these chemical messengers play in modulating neural circuits and physiological behaviors. A bioanalytical platform has been constructed for high-definition sequencing, spatial distribution mapping, quantitative profiling, and functional analysis of novel neuropeptides, which includes bottom-up and top-down MS, MALDI imaging, ion mobility spectrometry, isotopic quantitative labeling, bioinformatics tools, data independent acquisition, etc. These studies fill technical gaps of identifying large signaling peptides (> 4 kDa) from organisms without a sequenced genome, improving the throughput and accuracy of quantitative peptidomics, probing the component of fragment ion isomers in gas-phase, and rapidly discriminating D-amino acid-containing peptide epimers. The MS-based functional analysis reveals the signaling pathways of these biomolecules and provides new insight into the neuroendocrine regulation of mental disorder and biomarker discovery of neurodegenerative diseases.
Quantitative Proteomics and Native Top-down Mass Spectrometry: Our research also focus on the study of protein arginine dimethylation and its implication in cancer by quantitative proteomic approaches and native mass spectrometry. We are developing a novel SILAC-based strategy by simultaneously incorporating various stable isotope labeled amino acids into proteins during cell culture, which allows site-specific characterization of dimethylarginine. We are applying this new strategy to screen the substrates of co-activator arginine methyltransferase (CARM1) in cancer cells. The results improve our understanding of how deregulated CARM1 function is implicated in cellular processes. Furthermore, we are developing improved native MS and ion mobility spectrometry protocols and methodologies to investigate the structures of the protein complex associated with apoptosis and proliferation of cancer cells.
- Jia C, Wu Z, Lietz CB, Liang Z, Cui Q and Li L* (2014) Gas-Phase Ion Isomer Analysis Reveals the Mechanism of Peptide Sequence Scrambling. Anal Chem. 86: 2917-2924. (Cover Story)
- Jia C, Lietz CB, Yu Q and Li L* (2014) Site-Specific Characterization of D-Amino Acid-Containing Peptide Epimers by Ion Mobility Spectrometry. Anal Chem. 86: 2972-2981. (Cover Story and “ACS Editors’ Choice”)
- Jia C, Hui L, Cao W, Lietz CB, Jiang X, Chen R, Catherman AD, Thomas PM, Ge Y, Kelleher NL and Li L* (2012) High-definition De Novo Sequencing of Crustacean Hyperglycemic Hormone (CHH)-family Neuropeptides. Mol Cel Proteomics 11:1951-1964.
- Jia C, Yu Q, Wang J and Li L* (2014) Qualitative and Quantitative Top-down Mass Spectral Analysis of Crustacean Hyperglycemic Hormones in Response to Feeding. Proteomics. 14:1185-1194. (A special issue for “top-down proteomics”
- Jia C, Lietz CB, Ye H, Hui L, Yu Q, Yoo S and Li L* (2013) A Multi-Scale Strategy for Discovery of Novel Endogenous Neuropeptides in the Crustacean Nervous System. J Proteomics 91:1-12.
- Jia C, Qi W* and He Z (2007) Cyclization Reaction of Peptide Fragment Ions During Multistage Collisionally Activated Decomposition: An Inducement to Lose Enternal Amino-acid Residues. J Am Soc Mass Spectrom 18:663-678.
- Jia C, Qi W*, He Z and Qiao B (2006) Multi-stage Collisionally-Activated Decomposition in an Ion Trap for Identification of Sequences, Structures and b(n) -> b(n-1) Fragmentation Pathways of Protonated Cyclic Peptides. Eur J Mass Spectrom 12:235-245.
- Jia C, Qi W*, He Z, Yang H and Qiao B (2006) Synthesis of Heptapeptides and Analysis of Sequence by Tandem Ion Trap Mass Spectrometry. Cent Eur J Chem 4:285-298. 9. Jia C, Qi W*, He Z and Qiao B (2006) Sequencing Peptides by Electrospray Ion-Trap Mass Spectrometry: A Useful Tool in Synthesis of Axinastatin 3. Cent Eur J Chem 4:620-631.