Our team is focusing on the signaling transduction pathway mediated translational medical research that aims to answer the clinically raised fundamental pathological questions from the basic research perspective and fulfill unmet medical needs from drug discovery point of view.To do this, we integrate multiple disciplines such as Chemistry, Biochemistry, Medicinal Chemistry, Chemical Biology, Structural Biology, Molecule Biology, Pharmacology, Bioinformatics and Pathology into the whole chain of drug discovery pipeline by application of Structural Based Drug design, Computer Aided Drug Design, NMR Mediated Fragment Based Drug Design, High Throughput Drug Screening and Combination Drug Regime Design technologies or concepts.We are specially interested in the kinase associated deregulated signaling transduction pathway in variety of disease contexts and try to employ the newly in house developed small molecule probes to address the fundamental pathological questions such as tumorigenesis and drug resistance mechanisms and subsequently develop the small molecule drugs to control the diseases.
Specifically, our research is divided into three different but related areas.
1. Small molecule probes discovery and development: We are trying to apply the SBDD, FBDD and CADD as well as chemical informatics strategies to develop variety of different mechanism based small molecule probes such as irreversible protein binding probes, reversible DNA replicating probes etc. In the meanwhile, we are validating the therapeutic potential of biological targets by application of such probes via the proof of concept preclinical evaluation and subsequently developing drug like candidate for the clinical trials.
2. Drug resistance mechanistic study: we are trying integrating the Chemical Biology and Molecule Biology to address the drug resistance problems in the clinic. Both the drug treatment induced on target acquired mutation resistance and intrinsic signal pathway adaptive resistance are critical fundamental problems for target therapies. By employing chemical genetics approaches in the complementary of traditional genetic technologies we try to reveal the basic mechanisms of such problems and in the meanwhile employing system biology concept to search for the rational drug combination therapies to confer the drug resistance via high throughput screening and knowledge based combination design.
3.Natural products drugs re-discovery: Chinese herbal regimes have provides a huge library of the bio-active natural product/s and have been validated in the long history of herbal occupied clinical application. We are trying to employ the new system biology concept and integrate the NMR, LC-MS and high throughput screening based technologies to study the proper bio-active ingredients combinations and in the meanwhile reveal the mechanism from the systematic signal transduction pathway network point of view.
