The Molecular Medicine (Small Molecule Science) Platform is a fusion of medicinal chemistry, natural products chemistry, Traditional Chinese Medicine and pharmaceutical analysis. While each of these areas has its own identity and interests, the platform concept recognizes that there are many reasons for overlap between the areas, and these overlapping interests represent opportunities for collaborative research, leveraging the strengths of each discipline to build a discovery program that is greater than the sum of its parts. Modern research is inherently collaborative, so it is essential that we create a research environment that stimulates collaboration among a variety of scientists, allowing our students to learn how best to leverage the skills and knowledge of their colleagues and teachers to help solve their own research problems.
Nature is a rich source of novel molecules possessing complex biological activities. Most drugs used in Western medicine are either naturally occurring or are based on a natural product. The natural product chemist typically isolates interesting molecules having a biological activity and then identifies their chemical structure using a variety of spectroscopic and chemical methods. The medicinal chemist may then take such a lead structure, and synthesize it and related compounds to define the relationship between biological activity and structural features of the molecule. This structure-activity relationship (SAR) can be further refined via modular or combinatorial synthesis of libraries of closely related compounds, eventually leading to a drug candidate compound. The integration of Traditional Chinese Medicine into what could be described as a Western drug discovery program is an interesting and exciting opportunity. Most of the world’s population relies on some form of traditional medicine for their healthcare needs. While there is ample evidence that many traditional medical practices are effective in treating diseases, many in the West still consider them to be primitive and inferior to Western “modern” medicine. This misperception stems from the fact that science simply does not understand how or why traditional medicines work. Using the tools of natural products chemistry and modern analytical chemistry to study TCM will help us to understand the molecular basis of these useful and effective treatments. The Molecular Medicine Platform is a fusion of the various chemical disciplines involved in pharmaceutical research and development. In order to be a real drug discovery program, we rely on collaborations with the other, more biologically or biochemically focused platforms to develop and explore the pharmacologic targets that make chemistry relevant to treating disease.
The research of the Borris groups involves a) Validation of traditional medical practices, b) Discovery of novel biologically active natural products, c) Natural products used as dietary supplements, d) Phytochemical systematics, e) Application of NMR spectrometry to the structure determination of natural products, and f) Applications of high performance centrifugal partition chromatography to the isolation of biologically active natural products and other organic compounds.
Mycology, Biotechnology, and Synthetic Biology
Many valuable microbes are not usually evolved to produce desired products and this necessitates the need to improve/maximize their metabolic and regulatory networks through genetic engineering. The main aim of our research in Mario's laboratory of yeast synthetic biology is to re-engineer some key metabolic pathways from filamentous fungi into Saccharomyces cerevisiae (yeast) cells in other to enhance its abilities to synthesis natural products (NPs). Metabolic pathways associated with NPs are usually encoded into clusters of genes (biosynthetic gene clusters—BGCs) while the traditional methods for the integration of genes into the yeast genome rely on homologous recombination at the loci of auxotrophic markers. Our project is designed to establish a reliable protocol for the integration of multiple genes into the yeast genome in a single “shot” through CRISPR-Cas9 or CRISPR-Cas12a system with which allows multiple-integration protocol. This will allow us to build a different type of synthetic gene circuits such as complex digital transcription networks for application as biosensors, molecular classifiers, and DNA computing.
We are considering a pilot comparative study by assembling in yeast, the “natural” and a “retrosynthetic” gene cluster for a well-known NPs from different filamentous fungi, which grow in extreme conditions. We are also looking at a different way to enhancing their production. In this case, new transcriptional activators for these NPs are designed via the CRISPR-dCas9 system, where dCas9 means “deficient Cas9” i.e. a Cas9 stripped of its nuclease activity. Guide RNA molecules would be designed such that they bind only in the proximity of the target promoter without any off-target effects that could lead even to cell death. This issue might force us to consider other nuclease-deficient proteins (e.g. dCas12a) that bind the DNA in the presence of protospacer adjacent motifs (PAMs) distinct from those recognized by dCas9 (NGG and NAG). Finally, activation of transcription is optimized by fusing different activation domains, such as VPR and VP64, to the chosen deficient Cas protein.
The research of the Bao group involves 1) development of new analytical technologies, such as (a) wide bore electrophoresis (WBE), which increases sample loading significantly compared to capillary electrophoresis (CE) for better detection and easy interface with MS and other technologies;(b) WBE containing microchip systems; and (c) multi-dimensional separation systems; 2)development of innovative bio/analytical methods such as affinity CE and liquid phase microextraction (LPME) for proteomics and pharmaceutical analysis; 3) development of new separation media including various silica gel, polymeric resin, and even agarose gel based resins and their applications; and 4)new development of miniaturized and high throughput sample preparation techniques, such as fritless SPE, membraneSPE, supported liquid extraction (SLE) and fast protein precipitation, etc.
The research in the Bureik group encompasses two primary areas:
1) The study of human drug metabolizing enzymes and their use for organic synthesis.
A major goal in this project involves systematic testing of all variants of drug metabolizing cytochrome P450 enzymes (CYPs or P450s) and UDP glycosyltransferases (UGTs) identified in Chinese patients. This is expected to aid doctors in choosing the correct dosage for patients.
2) Investigation of human CYP4Z1 and exploitation of its activity for the treatment of breast cancer.
In this project, we have successfully identified CYP4Z1 to catalyze fatty acid in-chain hydroxylase and also ether cleavage. A primary aim is to search for compounds that can act as CYP4Z1-activated prodrugs and have potential for treatment of breast cancer.
Recently published work:
In cooperation with the group of Prof. Gerhard Wolber (Free University Berlin, Germany) we recently published a homology model of a UGT1A5 variant (UGT1A5*8) which shows that the cofactor UDP-GA is placed in a much more favorable geometry in UGT1A5*8 as compared to the wild-type, thus explaining its increased catalytical activity (Yang et al., 2018):
(A) Structural homology model for UGT1A5*8 with bound cofactor Uridine-diphosphoglucoronic acid (UDP-GA). The secondary structure ribbon is shown in grey. Helix Q is highlighted in blue. The cofactor (colored turquois) is situated in the catalytic cleft between the N-terminal (left) and C-terminal (right) domains. (B) Superposition of C-terminal domains of the UGT2B7 crystal structure (yellow) and UGT1A5*8 homology model (grey) with a root-mean square root of 2. 1 Å. (C) Cofactor protein interaction diagram for UGT1A5 and UDP-GA. The glucuronic acid moiety of UDP-GA is hold in place by electrostatic interaction with Arg174 and hydrogen bonding to Ser376 and Asp397. The uridine-diphosphate moiety forms hydrogen bonds to Ser307, Leu308, His373, His377 and Gly378. Blue double-headed arrow represents electrostatic interaction. Red arrows represent hydrogen bond acceptance and green arrow hydrogen bond donation.
The research of the Chen group concerns isolation, identification, bioactivity, and mechanism of constituents from natural resources. In particular, the group focuses on functional mechanism and structure-activity relationships of macromolecules (polysaccharides and proteins) as well as small biomolecules. Methods are being developed in the group to quantify bioactivity of polysaccharides and small biomolecules from Traditional Chinese Medicine and natural resources. Additionally, the group investigates functional food and new medicine from natural sources.
Her research would be helpful to the investigation and utilization of natural resources. She has been the Primary Investigator (PI) in 15 projects such as the funds from National Natural Science Foundation of China (NSFC), National High Technology Research and Development Program ("863"Program) of China, Project of National Key Technology Research and Development Program for The 12th Five-year Plan, National Program on Key Basic Research Project (973 Program). More than 100 research papers of Dr. Haixia Chen have been published, and 73 of the papers are published on SCI/SCIE journals with Haixia Chen being the first author or correspondence author. She has participated in 8 published books. 35 Chinese patents have been applied and 17 of them were authorized. Her papers on the study of bioactive polysaccharides have been cited by many researchers around the world and the citation frequency reached 2200 times in SCI database with H index of 25. One of her paper has been cited more than 225 times at the end of April 2019. She has been the editorial board member of some journals such as EC Pharmacology and Toxicology, Journal of Food Safety & Quality, Pharmarceutical Journal of Chinese People’s Liberationl Armay. She has also been the reviewer of NSFC, MOST and MOE and many international journals and Chinese journals such as Frontiers in Pharmacology, Food Chemistry, Carbohydrate Polymers, International Journal of Biological Macromolecules, Food research international, Journal of Agricultural and Food Chemistry etc.
The research of the Chen group is focused on synthesis of biomaterials and development of modern separation and analysis technology. In particular, efforts include a) development of different methods to control the morphology and pore structure of the HPLC stationary phase, b) design mixed-mode chromatography (MMC) according to the structure of analytes and investigation into their mechanism, and c) exploitation of magnetic separation technology in the purification of biological samples. Additionally, efforts are extended towards chiral analysis of pharmacological compounds, including synthesis of chiral stationary phase of HPLC, and optimization of separation and identification methods in HPLC and LC-MS.
Our research is focused on developing and implementing proteomic strategies to gain new insights into the molecular mechanisms of diseases, especially cancer. The topics we are interested about are listed below.
1) To decipher the interactions between biological macromolecules, such as protein-protein interactions and long non-coding RNA (lncRNA)-protein interactions, by combing affinity purification, biological mass spectrometric analysis and bioinformatics, and also to understand their implications in cancer.
2) Systematic and comprehensive molecular profiling of tumor by multi-omics, integrating data from genetics, transcriptomics, proteomics, metabolomics, etc.
3) Single cell protein analysis. We employ a state-of-the-art technology called mass cytometry to analyze protein expressions in single cells. Multiplex analytical panels are designed to achieve precise sub-clustering of immune cells in the tumor microenvironment and to understand tumor heterogenesis.
Research in the Clark group focuses on microbial natural products as applied to drug discovery, metabolomics, and chemical ecology. Microbes have long been a source of potent antimicrobial and anticancer agents, and we have a particular interest in marine and extremophilic microbes as a source of new drug leads. We also investigate chemical ecology: what role the metabolites serve for the microbe itself, and how are they involved in the interaction of microbes with other organisms. The group uses molecular networking and multivariate statistical techniques in all of these research avenues in order to classify samples, identify active components, and elucidate the interactions of molecules and organisms. While microbes are the primary focus of the group we also have experience working with plants and marine organisms, if there are particularly interesting ecological questions to be addressed in these areas.
The research efforts of the Dai group encompass two areas: 1) The role of retinoid-related orphan receptor RORα in controlling skin homeostatis, and 2) Control of normal mitosis by protein kinase haspin. In the first area, the main interest is on the interplay between intra- and inter-cellular signaling pathways involved in control of skin tissue homeostasis and tumor development. Focuses on the role of the nuclear orphan receptor RORα in controlling keratinocyte differentiation and skin tumor formation, as well as the therapeutic potential of RORα agonists/antagonists in treatment of skin diseases. In the second area, the group is interested in exploring the role of haspin in cancer development and the potential of haspin inhibitors as anti-tumor drugs.
The research area of the Du group involves investigation of hypervalent iodine (III) – mediated transformations, including oxidative coupling, rearrangement, cascade reactions, and asymmetric reactions. Additionally, the group develops metal-free methodology for the constructionof heterocyclic compounds and pharmaceutical agents.
The research of the Gao group encompasses three main areas, including 1) Production of active constituents by biotechnology in medicinal plants, b) Development of functional products from Traditional Chinese Medicine and natural products, and c) Development of new drugs from Traditional Chinese Medicine and natural products.
MICROBIAL BIOTECHNOLOGY
NANOBIOTECHNOLOGY
Design and synthesis of novel Cholera Toxin inhibitor based on the rim-differentiated C5-symmetrical Tiara-Pillar[5]arene scaffold.
Gold(III) and gold(I) complexes with anti-tumour activity with similar structures to Auranofin and cis-platin.
The 'hardness' and 'softness' of metal ions and ligands correlates with their polarizabiliry: Metal ions which are small and highly charged e.g. Au(III), and ligands which are small and electronegative, are 'hard', Large, polarizable metal ion or ligand donor atoms are 'soft', The trans-influence is the influence that a ligand has on the strength of the metal-ligand bond trans to itself and increases with the softness of the influencing ligand and influences drug activity. The sequence of increasing softness of some common ligands is: Cl- < Br- < RS- < R3P <ylide < Ar- < R-. Our research has thus been aimed at synthesising similar molecules to test for their anti-tumour properties.
Identification and characterization of new enzymes and new metabolic pathways in nature using a combination of bioinformatics, genetic, biochemical and biophysical methods.
The research of the Jiang group includes, a) carbohydrate chemistry with the use of sugars as chiral starting materials in synthesis, b) studies on the shikimic acid and shikimate pathway with particular interests in designing enzyme inhibitors as potential antimicrobial agents against bacterial, fungal and parasitical pathogens, c) process research and development for Active Pharmaceutical Ingredients and related intermediates in collaboration with industry, and d) development of fluorine-18 labelled radiopharmaceuticals used in Positron Emission Tomography
Wang’s research addresses production of traditional Chinese medicine (TCM) active compounds through biotechnology. 1. Analysis of TCM active compounds biosynthesis pathway. 2. Studies on TCM active compounds metabolism regulation. 3. Large scale tissue culture of TCM active compounds.
The research in the group of Li involves investigations into Traditional Chinese Medicines (TCM). The emphasis is on the genetic relationship among medicinal plants based on macromolecules, such as starch and polysaccharides, and the development of process techniques for herbal materials. Additionally, the group is involved in the development of functional foods from TCM and their effective constituents. Functional products with throat clearing, hypoglycemic, hypolipidemic and aperient bowel functions have been developed.
Li’s research addresses development and application of electrophoresis techniques,heterogeneous catalysis and applications, chiral separation and applications, sample preparation and applications, and high throughput drug screening based on hollow fiber member system development.
Supramolecular Chemistry
The research in the group of Olson is focused on systems chemistry with emphasis in surface science/surface chemistry and molecular recognition and self-assembly. Focus is on the role of long-range non-covalent interactions and electrostatics in synthetic macromolecules and how these forces affect the thermodynamic equilibrium and kinetics of self-assembly in solution, on surfaces, and at the solvent-nanoparticle interface. Specific directions include, 1) development of functional information of rich structural motifs and investigation of their performance characteristics in solution as molecular entities, 2) carry over of successful systems into the macromolecular world of polymer scaffolds, colloids, and nanoparticulates, eventually leading to 3) incorporation of these macromolecular components into device setting.
Supramolecular chemistry
Natural Product Drug Discovery, Pharmacognosy
My research fields span from pollination and insect behavioral ecology, the reproductive biology of orchids, plant-animal interactions through floral cues, and pollination applied to agroecological models. Key crops on which I worked are native Vanilla and Cacao. I have also investigated the composition, biodiversity, and human health implications of bee products and food sources; among these honey, bee venom, nectar, pollen, and ground-nesting bees' provision.
The research in the group of Srinivasan encompasses two main areas, 1) Developing new reaction methodologies: The research topics under this area include bioorthogonal reactions, late-stage modification of advanced chemical entities, C-H activation, and high-throughput amenable synthesis – aiming at advancing the way organic molecules are made for drug discovery and chemical biology applications. 2) Inhibitor discovery based on fragment-based approaches: Design and synthesis of ‘unconventional’ fragments with rich structural diversity. These fragments will be used as a starting point towards novel inhibitors for unexplored biological targets such as the AurB-INCENP interaction.
The research in the group of Su encompasses three main areas, including a) Isolation and identification of bioactive natural compounds from medicinal plants, b) Quality control of traditional chinese medicines, 3) Research & development of new medicines of natural origin
Asymmetric Synthesis.
Organocatalysis.
Organometallic Catalysis.
SuFEx Chemistry.
Developing innovative synthetic methodologies in photo-catalysis and earth-abundant
metal catalysis, with particular interest in constructing organo-fluorine compounds
and related drug modifications.
Supramolecular chemistry
Exploration of Stereoselective Processes, and Applications to Medicinal Chemistry
Development of new stereoselective approaches to the synthesis of medicinally important heterocycles specifically nuclear substituted 3,3′-disubstituted oxindole’s and oxazaridines, thalidomide’s, other biologically important molecules via the C-N, C-O bond formation strategies
Extractions, purification and biological characterization of sea anemone's native toxins.
Recombinant techniques of peptides and peptide synthesis.
Structural elucidation of peptides by NMR.
The research in the group of Wang encompasses four main areas, including 1) Functional polymeric materials (biodegradable polymeric materials, smart polymeric materials such as thermo-sensitive and pH sensitive polymers, dendrimers etc.), 2) Nanotechnology for solubility improvement of water-insoluble drugs, 3) Targeted and controlled drug release systems, and 4) Self-assembled nanostructures for controlled drug release.
The research in the group of Wang involves the design, synthesis, and biological activity evaluation of new compounds, with focus on industrialization of generic drugs, intermediates, and fine chemicals. Specific areas include 1) Design and synthesis of the Rho kinase inhibitor, 2) Design and synthesis of the PDE4 inhibitor, and 3) Design and synthesis of antihistamine drugs
To support the projects of the research groups in the SPST by offering a state-of-the-art X-ray crystallography facility.
To contribute to the study of diffuse scattering and defect structure simulation by developing new and improving existing methods.
To understand the structure of crystalline materials and the relationships between the structure and properties of these materials.
The research in the group of Yang involves the fields of natural products, medicinal chemistry and biochemistry research focused at the discovery and development of bioactive natural products and their analogs as clinical trials drug candidates. Work is carried out to understand the relationship between bioactive constituents and therapeutic effects of traditional Chinese medicine. Using basic natural products and medicinal chemistry principles coupled with modern technologies, including new analytical techniques, computational techniques, and mechanism of action or target-based medicinal chemistry research evaluation methods, the group works towards discovery and development of potential therapeutic drugs and functional foods.
Natural Products Chemistry is the science that studies the secondary metabolites present in living organisms and their possible use in different fields, mostly in pharmaceutic as a new drugs. In the last 3 decades 53% of the compounds developed as new medicines are related to natural products as lead compounds, as a starting material for semi-synthetic drugs or as inspiration for the synthesis of natural product mimics.
We focus our research in microbial natural products, which are an excellent source of new biologically active compounds. The starting point of the research is the collection of microorganism samples following the culture of the microorganisms, isolation of pure microbial strains, identification, extraction and biological testing of such. Biological active extracts are further more analyzed using GC-MS and LC-MS and compared with data bases as to concentrate efforts to the identification and isolation of new active compounds. Once active compounds have isolated, modification of the culture media and growing conditions of the microorganisms is done as to increase or decrease production of metabolites or even initiate the biosynthesis of others compounds that could present interesting biological activities.
The research in the group of Zhang is encompassed in the areas of chiral separation and proteomics analysis.
研究方向为疾病药物靶点发现、疾病诊断、安全评价等，承担和参与国家自然科学基金面上项目以及科技部、中医药管理局等重大研发计划，近5年作为主通讯作者在Hepatology、Nature Communications、JECCR等杂志上发表多篇SCI论文。担任美国毒理学会官方杂志《Toxicological Sciences》副主编、美国生物化学和分子生物学会杂志《Journal of Lipid Research》编委、国内杂志《Medicine Advances》编委。
Our group research interest lies in investigating basic mechanism of bio-active molecular (including nitric oxide, hydride and methyl et al.) transfer reaction in enzyme or in solution, with a goal of 1) design of more efficient chemical catalysis as well as the designed enzyme; 2) rational design of corresponding inhibitor/drug basing on the mechanism exploration. This inspiring research area requires the combination the application of physical organic chemistry, biochemistry, chemical biology and molecular biology.
The most recently work refers to the understanding the role of compaction in methyl transfer reactions with the target of finding how the molecular motion in enzymes would affect the catalytic ability in the methyl transfer reaction. This study about the methyl transfer system had/will extended from catechol-O-methyltransferase (COMT) to glycine-N-methyltransferase (GNMT), Nicotinamide N-Methyltransferase (NNMT) and DNA\RNA demethylation with various experimental approaches such kinetic isotope effect, binding isotope effect, time-resolved spectrometers, hydrogen deuterium exchange with mass spectrometry (HDX-MS) as well as computational simulation.
The research interests include 1) MS-based multi-omics studies of clinical tissues (PTC) – biomarker / target screening for diagnosis and drug discovery; 2) Mass spectrometry methodology in pharmaceutical analysis; 3) combinatorial studies of non-covalent interactions in gas-phase and in solution; 4) mechanistic studies of OM-mediated homogenous catalytic reactions.
medical chemistry，medical synthetic chemistry, organic chemistry, organic reaction mechanism research
药物化学，药物合成化学，有机化学，有机反应机理研究
for detail information please see our group page：
https://www.x-mol.com/groups/chunzhang
The research in the group of Zhou encompasses three main areas, including, 1) Investigation of molecular pathogenesis of diseases and cell signaling pathways, and pharmacological mechanism of drug action, 2) Development of new small molecule based targeting anticancer drugs, e.g., TRAF6 as a new target of anti-tumor therapy, 3) Development of cells and C. elegans models, for high-throughput screenings, e.g., anti-aging drugs.
The Molecular Medicine (Small Molecule Science) Platform is a fusion of medicinal chemistry, natural products chemistry, Traditional Chinese Medicine and pharmaceutical analysis. While each of these areas has its own identity and interests, the platform concept recognizes that there are many reasons for overlap between the areas, and these overlapping interests represent opportunities for collaborative research, leveraging the strengths of each discipline to build a discovery program that is greater than the sum of its parts. Modern research is inherently collaborative, so it is essential that we create a research environment that stimulates collaboration among a variety of scientists, allowing our students to learn how best to leverage the skills and knowledge of their colleagues and teachers to help solve their own research problems.
Nature is a rich source of novel molecules possessing complex biological activities. Most drugs used in Western medicine are either naturally occurring or are based on a natural product. The natural product chemist typically isolates interesting molecules having a biological activity and then identifies their chemical structure using a variety of spectroscopic and chemical methods. The medicinal chemist may then take such a lead structure, and synthesize it and related compounds to define the relationship between biological activity and structural features of the molecule. This structure-activity relationship (SAR) can be further refined via modular or combinatorial synthesis of libraries of closely related compounds, eventually leading to a drug candidate compound. The integration of Traditional Chinese Medicine into what could be described as a Western drug discovery program is an interesting and exciting opportunity. Most of the world’s population relies on some form of traditional medicine for their healthcare needs. While there is ample evidence that many traditional medical practices are effective in treating diseases, many in the West still consider them to be primitive and inferior to Western “modern” medicine. This misperception stems from the fact that science simply does not understand how or why traditional medicines work. Using the tools of natural products chemistry and modern analytical chemistry to study TCM will help us to understand the molecular basis of these useful and effective treatments. The Molecular Medicine Platform is a fusion of the various chemical disciplines involved in pharmaceutical research and development. In order to be a real drug discovery program, we rely on collaborations with the other, more biologically or biochemically focused platforms to develop and explore the pharmacologic targets that make chemistry relevant to treating disease.
The research of the Borris groups involves a) Validation of traditional medical practices, b) Discovery of novel biologically active natural products, c) Natural products used as dietary supplements, d) Phytochemical systematics, e) Application of NMR spectrometry to the structure determination of natural products, and f) Applications of high performance centrifugal partition chromatography to the isolation of biologically active natural products and other organic compounds.
1，Synthesis of plant natural products
2，Glycyl radical enzymes
3，Cyanophages
Mycology, Biotechnology, and Synthetic Biology
Many valuable microbes are not usually evolved to produce desired products and this necessitates the need to improve/maximize their metabolic and regulatory networks through genetic engineering. The main aim of our research in Mario's laboratory of yeast synthetic biology is to re-engineer some key metabolic pathways from filamentous fungi into Saccharomyces cerevisiae (yeast) cells in other to enhance its abilities to synthesis natural products (NPs). Metabolic pathways associated with NPs are usually encoded into clusters of genes (biosynthetic gene clusters—BGCs) while the traditional methods for the integration of genes into the yeast genome rely on homologous recombination at the loci of auxotrophic markers. Our project is designed to establish a reliable protocol for the integration of multiple genes into the yeast genome in a single “shot” through CRISPR-Cas9 or CRISPR-Cas12a system with which allows multiple-integration protocol. This will allow us to build a different type of synthetic gene circuits such as complex digital transcription networks for application as biosensors, molecular classifiers, and DNA computing.
We are considering a pilot comparative study by assembling in yeast, the “natural” and a “retrosynthetic” gene cluster for a well-known NPs from different filamentous fungi, which grow in extreme conditions. We are also looking at a different way to enhancing their production. In this case, new transcriptional activators for these NPs are designed via the CRISPR-dCas9 system, where dCas9 means “deficient Cas9” i.e. a Cas9 stripped of its nuclease activity. Guide RNA molecules would be designed such that they bind only in the proximity of the target promoter without any off-target effects that could lead even to cell death. This issue might force us to consider other nuclease-deficient proteins (e.g. dCas12a) that bind the DNA in the presence of protospacer adjacent motifs (PAMs) distinct from those recognized by dCas9 (NGG and NAG). Finally, activation of transcription is optimized by fusing different activation domains, such as VPR and VP64, to the chosen deficient Cas protein.
The research of the Bao group involves 1) development of new analytical technologies, such as (a) wide bore electrophoresis (WBE), which increases sample loading significantly compared to capillary electrophoresis (CE) for better detection and easy interface with MS and other technologies;(b) WBE containing microchip systems; and (c) multi-dimensional separation systems; 2)development of innovative bio/analytical methods such as affinity CE and liquid phase microextraction (LPME) for proteomics and pharmaceutical analysis; 3) development of new separation media including various silica gel, polymeric resin, and even agarose gel based resins and their applications; and 4)new development of miniaturized and high throughput sample preparation techniques, such as fritless SPE, membraneSPE, supported liquid extraction (SLE) and fast protein precipitation, etc.
The research in the Bureik group encompasses two primary areas:
1) The study of human drug metabolizing enzymes and their use for organic synthesis.
A major goal in this project involves systematic testing of all variants of drug metabolizing cytochrome P450 enzymes (CYPs or P450s) and UDP glycosyltransferases (UGTs) identified in Chinese patients. This is expected to aid doctors in choosing the correct dosage for patients.
2) Investigation of human CYP4Z1 and exploitation of its activity for the treatment of breast cancer.
In this project, we have successfully identified CYP4Z1 to catalyze fatty acid in-chain hydroxylase and also ether cleavage. A primary aim is to search for compounds that can act as CYP4Z1-activated prodrugs and have potential for treatment of breast cancer.
Recently published work:
In cooperation with the group of Prof. Gerhard Wolber (Free University Berlin, Germany) we recently published a homology model of a UGT1A5 variant (UGT1A5*8) which shows that the cofactor UDP-GA is placed in a much more favorable geometry in UGT1A5*8 as compared to the wild-type, thus explaining its increased catalytical activity (Yang et al., 2018):
(A) Structural homology model for UGT1A5*8 with bound cofactor Uridine-diphosphoglucoronic acid (UDP-GA). The secondary structure ribbon is shown in grey. Helix Q is highlighted in blue. The cofactor (colored turquois) is situated in the catalytic cleft between the N-terminal (left) and C-terminal (right) domains. (B) Superposition of C-terminal domains of the UGT2B7 crystal structure (yellow) and UGT1A5*8 homology model (grey) with a root-mean square root of 2. 1 Å. (C) Cofactor protein interaction diagram for UGT1A5 and UDP-GA. The glucuronic acid moiety of UDP-GA is hold in place by electrostatic interaction with Arg174 and hydrogen bonding to Ser376 and Asp397. The uridine-diphosphate moiety forms hydrogen bonds to Ser307, Leu308, His373, His377 and Gly378. Blue double-headed arrow represents electrostatic interaction. Red arrows represent hydrogen bond acceptance and green arrow hydrogen bond donation.
The research of the Chen group concerns isolation, identification, bioactivity, and mechanism of constituents from natural resources. In particular, the group focuses on functional mechanism and structure-activity relationships of macromolecules (polysaccharides and proteins) as well as small biomolecules. Methods are being developed in the group to quantify bioactivity of polysaccharides and small biomolecules from Traditional Chinese Medicine and natural resources. Additionally, the group investigates functional food and new medicine from natural sources.
Her research would be helpful to the investigation and utilization of natural resources. She has been the Primary Investigator (PI) in 15 projects such as the funds from National Natural Science Foundation of China (NSFC), National High Technology Research and Development Program ("863"Program) of China, Project of National Key Technology Research and Development Program for The 12th Five-year Plan, National Program on Key Basic Research Project (973 Program). More than 100 research papers of Dr. Haixia Chen have been published, and 73 of the papers are published on SCI/SCIE journals with Haixia Chen being the first author or correspondence author. She has participated in 8 published books. 35 Chinese patents have been applied and 17 of them were authorized. Her papers on the study of bioactive polysaccharides have been cited by many researchers around the world and the citation frequency reached 2200 times in SCI database with H index of 25. One of her paper has been cited more than 225 times at the end of April 2019. She has been the editorial board member of some journals such as EC Pharmacology and Toxicology, Journal of Food Safety & Quality, Pharmarceutical Journal of Chinese People’s Liberationl Armay. She has also been the reviewer of NSFC, MOST and MOE and many international journals and Chinese journals such as Frontiers in Pharmacology, Food Chemistry, Carbohydrate Polymers, International Journal of Biological Macromolecules, Food research international, Journal of Agricultural and Food Chemistry etc.
The research of the Chen group is focused on synthesis of biomaterials and development of modern separation and analysis technology. In particular, efforts include a) development of different methods to control the morphology and pore structure of the HPLC stationary phase, b) design mixed-mode chromatography (MMC) according to the structure of analytes and investigation into their mechanism, and c) exploitation of magnetic separation technology in the purification of biological samples. Additionally, efforts are extended towards chiral analysis of pharmacological compounds, including synthesis of chiral stationary phase of HPLC, and optimization of separation and identification methods in HPLC and LC-MS.
Our research is focused on developing and implementing proteomic strategies to gain new insights into the molecular mechanisms of diseases, especially cancer. The topics we are interested about are listed below.
1) To decipher the interactions between biological macromolecules, such as protein-protein interactions and long non-coding RNA (lncRNA)-protein interactions, by combing affinity purification, biological mass spectrometric analysis and bioinformatics, and also to understand their implications in cancer.
2) Systematic and comprehensive molecular profiling of tumor by multi-omics, integrating data from genetics, transcriptomics, proteomics, metabolomics, etc.
3) Single cell protein analysis. We employ a state-of-the-art technology called mass cytometry to analyze protein expressions in single cells. Multiplex analytical panels are designed to achieve precise sub-clustering of immune cells in the tumor microenvironment and to understand tumor heterogenesis.
Research in the Clark group focuses on microbial natural products as applied to drug discovery, metabolomics, and chemical ecology. Microbes have long been a source of potent antimicrobial and anticancer agents, and we have a particular interest in marine and extremophilic microbes as a source of new drug leads. We also investigate chemical ecology: what role the metabolites serve for the microbe itself, and how are they involved in the interaction of microbes with other organisms. The group uses molecular networking and multivariate statistical techniques in all of these research avenues in order to classify samples, identify active components, and elucidate the interactions of molecules and organisms. While microbes are the primary focus of the group we also have experience working with plants and marine organisms, if there are particularly interesting ecological questions to be addressed in these areas.
The research efforts of the Dai group encompass two areas: 1) The role of retinoid-related orphan receptor RORα in controlling skin homeostatis, and 2) Control of normal mitosis by protein kinase haspin. In the first area, the main interest is on the interplay between intra- and inter-cellular signaling pathways involved in control of skin tissue homeostasis and tumor development. Focuses on the role of the nuclear orphan receptor RORα in controlling keratinocyte differentiation and skin tumor formation, as well as the therapeutic potential of RORα agonists/antagonists in treatment of skin diseases. In the second area, the group is interested in exploring the role of haspin in cancer development and the potential of haspin inhibitors as anti-tumor drugs.
The research area of the Du group involves investigation of hypervalent iodine (III) – mediated transformations, including oxidative coupling, rearrangement, cascade reactions, and asymmetric reactions. Additionally, the group develops metal-free methodology for the constructionof heterocyclic compounds and pharmaceutical agents.
The research of the Gao group encompasses three main areas, including 1) Production of active constituents by biotechnology in medicinal plants, b) Development of functional products from Traditional Chinese Medicine and natural products, and c) Development of new drugs from Traditional Chinese Medicine and natural products.
MICROBIAL BIOTECHNOLOGY
NANOBIOTECHNOLOGY
Design and synthesis of novel Cholera Toxin inhibitor based on the rim-differentiated C5-symmetrical Tiara-Pillar[5]arene scaffold.
Gold(III) and gold(I) complexes with anti-tumour activity with similar structures to Auranofin and cis-platin.
The 'hardness' and 'softness' of metal ions and ligands correlates with their polarizabiliry: Metal ions which are small and highly charged e.g. Au(III), and ligands which are small and electronegative, are 'hard', Large, polarizable metal ion or ligand donor atoms are 'soft', The trans-influence is the influence that a ligand has on the strength of the metal-ligand bond trans to itself and increases with the softness of the influencing ligand and influences drug activity. The sequence of increasing softness of some common ligands is: Cl- < Br- < RS- < R3P <ylide < Ar- < R-. Our research has thus been aimed at synthesising similar molecules to test for their anti-tumour properties.
Identification and characterization of new enzymes and new metabolic pathways in nature using a combination of bioinformatics, genetic, biochemical and biophysical methods.
The research of the Jiang group includes, a) carbohydrate chemistry with the use of sugars as chiral starting materials in synthesis, b) studies on the shikimic acid and shikimate pathway with particular interests in designing enzyme inhibitors as potential antimicrobial agents against bacterial, fungal and parasitical pathogens, c) process research and development for Active Pharmaceutical Ingredients and related intermediates in collaboration with industry, and d) development of fluorine-18 labelled radiopharmaceuticals used in Positron Emission Tomography
Wang’s research addresses production of traditional Chinese medicine (TCM) active compounds through biotechnology. 1. Analysis of TCM active compounds biosynthesis pathway. 2. Studies on TCM active compounds metabolism regulation. 3. Large scale tissue culture of TCM active compounds.
Synthetic Organic Chemistry
Natural product synthesis
macrocyclisation
catalysis
The research in the group of Li involves investigations into Traditional Chinese Medicines (TCM). The emphasis is on the genetic relationship among medicinal plants based on macromolecules, such as starch and polysaccharides, and the development of process techniques for herbal materials. Additionally, the group is involved in the development of functional foods from TCM and their effective constituents. Functional products with throat clearing, hypoglycemic, hypolipidemic and aperient bowel functions have been developed.
Li’s research addresses development and application of electrophoresis techniques,heterogeneous catalysis and applications, chiral separation and applications, sample preparation and applications, and high throughput drug screening based on hollow fiber member system development.
Supramolecular Chemistry
The research in the group of Olson is focused on systems chemistry with emphasis in surface science/surface chemistry and molecular recognition and self-assembly. Focus is on the role of long-range non-covalent interactions and electrostatics in synthetic macromolecules and how these forces affect the thermodynamic equilibrium and kinetics of self-assembly in solution, on surfaces, and at the solvent-nanoparticle interface. Specific directions include, 1) development of functional information of rich structural motifs and investigation of their performance characteristics in solution as molecular entities, 2) carry over of successful systems into the macromolecular world of polymer scaffolds, colloids, and nanoparticulates, eventually leading to 3) incorporation of these macromolecular components into device setting.
Supramolecular chemistry
Natural Product Drug Discovery, Pharmacognosy
My research fields span from pollination and insect behavioral ecology, the reproductive biology of orchids, plant-animal interactions through floral cues, and pollination applied to agroecological models. Key crops on which I worked are native Vanilla and Cacao. I have also investigated the composition, biodiversity, and human health implications of bee products and food sources; among these honey, bee venom, nectar, pollen, and ground-nesting bees' provision.
The research in the group of Srinivasan encompasses two main areas, 1) Developing new reaction methodologies: The research topics under this area include bioorthogonal reactions, late-stage modification of advanced chemical entities, C-H activation, and high-throughput amenable synthesis – aiming at advancing the way organic molecules are made for drug discovery and chemical biology applications. 2) Inhibitor discovery based on fragment-based approaches: Design and synthesis of ‘unconventional’ fragments with rich structural diversity. These fragments will be used as a starting point towards novel inhibitors for unexplored biological targets such as the AurB-INCENP interaction.
The research in the group of Su encompasses three main areas, including a) Isolation and identification of bioactive natural compounds from medicinal plants, b) Quality control of traditional chinese medicines, 3) Research & development of new medicines of natural origin
Asymmetric Synthesis.
Organocatalysis.
Organometallic Catalysis.
SuFEx Chemistry.
Developing innovative synthetic methodologies in photo-catalysis and earth-abundant
metal catalysis, with particular interest in constructing organo-fluorine compounds
and related drug modifications.
Supramolecular chemistry
Exploration of Stereoselective Processes, and Applications to Medicinal Chemistry
Development of new stereoselective approaches to the synthesis of medicinally important heterocycles specifically nuclear substituted 3,3′-disubstituted oxindole’s and oxazaridines, thalidomide’s, other biologically important molecules via the C-N, C-O bond formation strategies
Extractions, purification and biological characterization of sea anemone's native toxins.
Recombinant techniques of peptides and peptide synthesis.
Structural elucidation of peptides by NMR.
The research in the group of Wang encompasses four main areas, including 1) Functional polymeric materials (biodegradable polymeric materials, smart polymeric materials such as thermo-sensitive and pH sensitive polymers, dendrimers etc.), 2) Nanotechnology for solubility improvement of water-insoluble drugs, 3) Targeted and controlled drug release systems, and 4) Self-assembled nanostructures for controlled drug release.
The research in the group of Wang involves the design, synthesis, and biological activity evaluation of new compounds, with focus on industrialization of generic drugs, intermediates, and fine chemicals. Specific areas include 1) Design and synthesis of the Rho kinase inhibitor, 2) Design and synthesis of the PDE4 inhibitor, and 3) Design and synthesis of antihistamine drugs
To support the projects of the research groups in the SPST by offering a state-of-the-art X-ray crystallography facility.
To contribute to the study of diffuse scattering and defect structure simulation by developing new and improving existing methods.
To understand the structure of crystalline materials and the relationships between the structure and properties of these materials.
The research in the group of Yang involves the fields of natural products, medicinal chemistry and biochemistry research focused at the discovery and development of bioactive natural products and their analogs as clinical trials drug candidates. Work is carried out to understand the relationship between bioactive constituents and therapeutic effects of traditional Chinese medicine. Using basic natural products and medicinal chemistry principles coupled with modern technologies, including new analytical techniques, computational techniques, and mechanism of action or target-based medicinal chemistry research evaluation methods, the group works towards discovery and development of potential therapeutic drugs and functional foods.
Natural Products Chemistry is the science that studies the secondary metabolites present in living organisms and their possible use in different fields, mostly in pharmaceutic as a new drugs. In the last 3 decades 53% of the compounds developed as new medicines are related to natural products as lead compounds, as a starting material for semi-synthetic drugs or as inspiration for the synthesis of natural product mimics.
We focus our research in microbial natural products, which are an excellent source of new biologically active compounds. The starting point of the research is the collection of microorganism samples following the culture of the microorganisms, isolation of pure microbial strains, identification, extraction and biological testing of such. Biological active extracts are further more analyzed using GC-MS and LC-MS and compared with data bases as to concentrate efforts to the identification and isolation of new active compounds. Once active compounds have isolated, modification of the culture media and growing conditions of the microorganisms is done as to increase or decrease production of metabolites or even initiate the biosynthesis of others compounds that could present interesting biological activities.
The research in the group of Zhang is encompassed in the areas of chiral separation and proteomics analysis.
研究方向为疾病药物靶点发现、疾病诊断、安全评价等，承担和参与国家自然科学基金面上项目以及科技部、中医药管理局等重大研发计划，近5年作为主通讯作者在Hepatology、Nature Communications、JECCR等杂志上发表多篇SCI论文。担任美国毒理学会官方杂志《Toxicological Sciences》副主编、美国生物化学和分子生物学会杂志《Journal of Lipid Research》编委、国内杂志《Medicine Advances》编委。
Our group research interest lies in investigating basic mechanism of bio-active molecular (including nitric oxide, hydride and methyl et al.) transfer reaction in enzyme or in solution, with a goal of 1) design of more efficient chemical catalysis as well as the designed enzyme; 2) rational design of corresponding inhibitor/drug basing on the mechanism exploration. This inspiring research area requires the combination the application of physical organic chemistry, biochemistry, chemical biology and molecular biology.
The most recently work refers to the understanding the role of compaction in methyl transfer reactions with the target of finding how the molecular motion in enzymes would affect the catalytic ability in the methyl transfer reaction. This study about the methyl transfer system had/will extended from catechol-O-methyltransferase (COMT) to glycine-N-methyltransferase (GNMT), Nicotinamide N-Methyltransferase (NNMT) and DNA\RNA demethylation with various experimental approaches such kinetic isotope effect, binding isotope effect, time-resolved spectrometers, hydrogen deuterium exchange with mass spectrometry (HDX-MS) as well as computational simulation.
The research interests include 1) MS-based multi-omics studies of clinical tissues (PTC) – biomarker / target screening for diagnosis and drug discovery; 2) Mass spectrometry methodology in pharmaceutical analysis; 3) combinatorial studies of non-covalent interactions in gas-phase and in solution; 4) mechanistic studies of OM-mediated homogenous catalytic reactions.
medical chemistry，medical synthetic chemistry, organic chemistry, organic reaction mechanism research
药物化学，药物合成化学，有机化学，有机反应机理研究
for detail information please see our group page：
https://www.x-mol.com/groups/chunzhang
The research in the group of Zhou encompasses three main areas, including, 1) Investigation of molecular pathogenesis of diseases and cell signaling pathways, and pharmacological mechanism of drug action, 2) Development of new small molecule based targeting anticancer drugs, e.g., TRAF6 as a new target of anti-tumor therapy, 3) Development of cells and C. elegans models, for high-throughput screenings, e.g., anti-aging drugs.
