Natural product is an important source of new drug. Innovative technologies are urgently necessary to address three key problems of natural product research, chemical complexity， reliability of traditional activity/toxicity assays, and complexity of pharmacology. Multi-dimensional preparative chromatography separates extracts of natural product into multiple fractions or pure compounds, thus enables establishment of a huge valuable sample library originated from natural products. Cellular label-free integrative pharmacology (CLIP) technology can simultaneously identify the phenotypic activity and target of active species in natural product. Biomimicry, like organ-on-a-chip, organoid, or 3D bioprinting, enables in vitro physiological or disease models that correlates animal testing or clinical trial, which is considered revolutionary to the drug discovery industry. We explore these new technologies, aiming to increase the efficiency of drug discovery from natural products.
Natural product is an important source of new drug. Innovative technologies are urgently necessary to address three key problems of natural product research, chemical complexity， reliability of traditional activity/toxicity assays, and complexity of pharmacology. Multi-dimensional preparative chromatography separates extracts of natural product into multiple fractions or pure compounds, thus enables establishment of a huge valuable sample library originated from natural products. Cellular label-free integrative pharmacology (CLIP) technology can simultaneously identify the phenotypic activity and target of active species in natural product. Biomimicry, like organ-on-a-chip, organoid, or 3D bioprinting, enables in vitro physiological or disease models that correlates animal testing or clinical trial, which is considered revolutionary to the drug discovery industry. We explore these new technologies, aiming to increase the efficiency of drug discovery from natural products.
Organ-on-a-chip
Organ-on-a-chip is an effort to fulfill the long sought desire of researchers who have imagined recreating tissues and organs by etching grooves on silicon or plastic wafers to engineer a microenvironment that mimics the complex and physiological conditions in real organs.It has been selected as one of “Top Ten Emerging Technologies of 2016” at World Economic Forum 2016. We have established liver-on-a-chip, intestinal chip, diabetes chip, etc., attempted to establish disease models of NASH, IBD, diabetes, cancer, arteriosclerosis, etc, and used these models to study the pharmacology, efficacy, toxicity, and pharmacokinetics of compounds from natural product.
3D Bioprinting
3D bioprinting is the application of additive manufacturing technology in biomedical area. Its ability lies in recreation of the organ’s or tissue’s physiological structures in vitro. Artificial organ or tissue fabricated by 3D bioprinting is a powerful tool for drug screening when it is combined with fluidic technology. We developed an extrusion-based 3D bioprinter and organ-specific bio-inks, printed artificial liver lobule, blood vessel, and breast tumor, etc., attempted to establish disease models of NASH, IBD, diabetes, cancer, arteriosclerosis, etc, and used these models to study the pharmacology, efficacy, toxicity, and pharmacokinetics of compounds from natural product.
Other directions
Multi-dimensional Preparative Chromatography
Prof. Xiuli Zhang established several different kinds of multi-dimensional preparative chromatography methods, which has been used in preparation of alkaloid, phenolic acid，anthraquinoneandflavones, and further built a library with more than 100,000 samples and screened >8000 samples by cellular label-free integrative pharmacology profiling technology in Dalian Institute of Chemical Physics, Chinese Academy of Sciences. The story is continued in Soochow University.
Organoid
An organoid is a miniaturized and simplified version of an organ produced in vitro in three dimensions that shows realistic micro-anatomy. We collaborated with Shanghai Jiaotong University and Shenzhen Institute of Geriatrics to develop personalized organoid-on-a-chip. The more is coming.
Cellular Label-free Integrative Pharmacology Profiling
Prof. Xiuli Zhang firstly employed CLIP technology in natural product research in Asia, established 36 GPCR target screening models, and developed a set of pharmacology research protocols for natural products in Dalian Institute of Chemical Physics, Chinese Academy of Sciences. The story is continued in Soochow University