Research Interest
1. Developing novel analytical methods for studying drug interactions
- Develop and establish novel analytical methods based on MS, such as ESI-MS，MALDI-MS and ICP-MS, to study the interaction between antitumor compounds and biological targets.
- Develop and establish secondary ion mass spectrometric imaging method to study the cellular uptake, distribution and destination of anticancer drugs inside cells.
2. Research and development of multi-targeted anticancer drugs
- Design and synthesis multi-targeted metal complexes targeting both key signal transduction proteins and DNA;
- In vitro and in vivo screening and evaluation of metal-based anti-tumour compounds;
- The structure-activity study of metal-based anti-tumour compounds;
- The pharmacological, toxicological, pharmacokinetic and metabolic studies of metal-based anti-tumour drugs;
3. Chemical biology study based on multi-functional molecular probes
- Design and develop multi-functional small-molecular probes that can recognize both specific signal transduction proteins and DNA;
- Study the interaction between the multi-functional molecular probes and the biological targets to explore the cellular signalling pathways and networks;
- Study the interactions between the multi-functional molecular probes and receptors and their regulation to the signal transduction network to discover and pharmacologically valuable and clinically promising lead compounds.
- Applying the multi-functional molecular probes to screen and identify biomarkers and drugable targets;
Current Research Projects
l 2012.1-2016.12, NSFC National Major Research Project on Scientific Instruments: High resolution and multi-functional chemical imaging system (21127901), 8.7 million CNY
l 2012.1-2016.12, NSFC Key Project：Methodology for investigations on interactions between regulating proteins and DNA damaged by drugs (21135006), 3 million CNY
l 2011.1-2013.12, NSFC Major International Cooperation Project: Methodology for interactromics of metal-based anticancer agents (21020102039)，2.6 million CNY
l 2010.1-2012.12, NSFC General Project: Investigation of interactions between organometallic ruthenium anticancer complexes and serum proteins (20975103), 0.35 million CNY
Resaerch Progresses
l We have successfully synthesized a series of ruthenium complexes by linking the cytotoxic organometallic ruthenium units with the derivatives of Gefitinib, a molecular targeting anticancer drug for treatment of a few types of tumors, through N-Ru bonds. A number of these compounds exhibit highly selective inhibition on EGF-stimulated growth of human breast cancer cell lines (MCF-7), representing a type of novel dual-targeting ruthenium anticancer complexes.
l To rapidly and cost-effectively screen the highly active protein kinase inhibitors, we have developed a MS-based method to quantify the phosphorylated substrates of protein kinases. This method applies the TiO2-nanoparticle deposited capillary column or TiO2 coated magnetic hollow mesoporous silicon spheres to enrich the phosphorylated peptide substrate of protein tyrosine kinase EGFR, and can also be applied to the in vitro screening of other types of protein kinase inhibitors.
l We developed bottom-up and top-down mass spectrometric method to qualitatively and quantitatively characterize the selective substitution and redox reactions of the metal-based anticancer complexes with proteins. The results provide theoretical bases for precisely tuning the reactivity of metal-based anticancer complexes with biological targets through diverse chemical synthesis.
l We also developed and established mass spectrometry based analytical methods to identify the binding sites of organometallic ruthenium anticancer complexes to DNA, and systematically studied the kinetics of interactions between organometallic ruthenium anticancer complexes and DNA, and the migration pathways of organometallic ruthenium anticancer complexes on DNA.
