Microbiology & Immunology platform focus on the microbiology & immunobiology issues to support the theoretical and methodological research on key pathogenic microorganisms and their pathogenesis and immune mechanisms, and to develop the bio-products (diagnosis reagents, vaccine, adjuvants, therapeutic drug and others) to control infectious diseases. The integrated M & I analysis platform will be constructed to support the life science research and to service the human health in the future.
Research fields:
1.Infection immunity: Structural and functions of viral genomes；Pathogenesis, innate immunity and immune evasion mechanisms of viral infections.
2.Microbial biology in human, animal, food, water and stress environments by epigenetics, comparative genomics and bioinformatics.
3.Regulation and adaptive evolution of key innate immune system during in different biological evolution. Enzymology of immune cells in viral infection and inflammation.
4.Sensing of MAMPs from bacteria, fungi, and viruses or DAMPs by immune PRRs and their compartments. Immune regulation roles of natural adjuvants (microbiota, natural components of commensal lactic acid bacteria, plants) or synthetic agonists on innate immunity.
5.Enzymology of immune cells in viral infection and inflammation. General scheme for the enrichment of microbial cells or biomarkers with affinity probes showed as following figure.
Innate immunity is the first line of host defense against invading pathogenic microorganisms, where type I interferon (IFN) production is initiated at the early stages and subsequently induces the expression of IFN-stimulated genes (ISGs) in an autocrine and paracrine manner, leading to the destruction of invading pathogens. In order to replicate and survive, viruses have evolved diverse strategies to evade IFN responses. One area of research in my laboratory is to understand the molecular mechanisms of evasion of innate immunity by pathogenic microorganisms.
Another goal of our research is to study the molecular mechanisms of severe fever with thrombocytopenia syndrome virus (SFTSV) and enteroviruss D68 pathogenesis.
Key scientific issues
1) Innate detection of viral pathogenic microorganisms;
2) The mechanism of ubiquitin in the antiviral signaling pathway;
3) The molecular mechanism of the generation and regulation of type I interferon and other important cytokines by natural immune activation;
4) The mechanism of cytokine secretion after natural immune activation;
l.Molecular mechanisms on pathogenesis and immunity of viruses and bacterial toxins.
2.The roles of cell-intrinsic restriction and recognition in innate immunity and inflammatory disease of viral infection.
3.Development the techniques for diagnosis and prevention of human and animal pathogenic microorganisms and their toxic products in food, water, and environment.
4.Functional genomics and engineering of resource microbes to promote human health.
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.
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 in the Chung group focuses on understanding the role of microglia in neuroinflammation. Inflammation is a key component of pathophysiology of both acute injuries and chronic diseases including Parkinson’s and Alzheimer’s. Microglia activation/chemotaxis is prerequisite for microglia function whether neuroprotective or inflammatory, making understanding essential for design of rational approaches for therapeutic modulation and regulation of microglia proliferation and chemotaxis. Emphasis is on control of activation/chemotaxis of resident microglia in the brain in early stages of neuroinflammation. Unraveling complex networks of signaling downstream of P2Y12 receptor during microglia chemotaxis is an important target. Elucidation of neurotoxic effects of microglia observed in depression is another area of research interests.
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.
Cytochrome P450 (CYP) monooxygenases, the nature’s most versatile biological catalysts have unique ability to catalyse regio-, chemo-, and stereospecific oxidation of a wide range of substrates under mild reaction conditions, thereby addressing a significant challenge in chemocatalysis. In the recent decades, the importance of CYPs is illustrated by the fact that they are responsible for the majority of Phase I reactions in human drug metabolism, and their substrates include a broad range of active pharmaceutical ingredients, environmental toxins, carcinogens, and food-derived chemicals. Therefore, a compilation of CYP monooxygenases is required for a rational comprehensive approach for elucidating the catalytic potentials and functional utilities of human CYPs for industrial approach. This urged us to generate the gene library of human cytochrome P450s to facilitate the glimpse of molecular mechanisms and metabolic diversity of P450s, thereby functionally explore and characterize the novel enzymes. Here I have listed the three major ongoing projects which I am currently engaged in Prof. Bureik's laboratory.
1. Construction of Human CYP Gene Library
2. Functional Expression of Human CYPs in Fission Yeast Reconstituted System
3. Systematic assessment of CYP-dependent metabolism with Differential Redox partners
The research of the Gao group covers medicinal chemistry and molecular targeting, synthetic chemistry and organo catalysis, and computer-aided drug design, aimed at the discovery of functional drug delivery carriers and understanding mechanisms of molecular targeting. Specific areas include a) strategies for development of small molecular anti-cancer drugs for targeted therapy, b) design and development of actively transportable small molecule drugs or protein-drug conjugates, c) discovery and development of novel drug-delivery carriers and pharmaceutics based on supramolecular chemistry, d) computer aided molecular design and modeling for innovative drug discovery and mechanistic study of drug transporters.
MICROBIAL BIOTECHNOLOGY
NANOBIOTECHNOLOGY
Identification and characterization of new enzymes and new metabolic pathways in nature using a combination of bioinformatics, genetic, biochemical and biophysical methods.
We are interested in understanding the DNA repair mechanism in the germline. Especially, we have focused on investigating the epigenetic regulation of DNA damage response and repair. We use a microscopic size nematode C. elegans and mammalian cells to study epigenetic control of DNA repair mechanism. 1. The role of conserved Epigenetic regulators in DNA repair and damage response. 2.The role of novel and conserved gene of DNA repair and damage response.
We are recuiting hard working students. Post-doc or Students interested in working in Genetics or Molecular biology in my lab, send an E-mail to hm.k @ duke.edu
1998年-2001年在天津泌尿外科研究所畅继武教授课题组所做的课题为肿瘤热休克蛋白90-肽复合物的提取纯化，并用该复合物诱导T细胞转化为特异性细胞毒性T淋巴细胞，为肿瘤的生物治疗进行基础研究。2001年继续以肿瘤特异性CTL为核心以树突状细胞转化特异性CTL为方法，进行治疗肿瘤的基础及临床应用的研究，该研究获得天津市科学技术进步奖二等奖。
Paramagnetic NMR, Pseudocontact Shifts, MS Spectrometry.
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Our laboratory is interested in the cellular innate immune events that sense viral infection and inhibit viral replication.
We are particularly focusing on the following two aspects: (1) endogenous suppressors that modulate innate immune signaling, and (2) molecular mechanism of autoimmune disorders caused by aberrant immune responses.
Lorenzo Pecoraro research group interests mainly focus on a) fungal and bacterial biotechnology, bioremediation, medicinal mushrooms b) microbial taxonomy and community ecology, network analysis c) environmental microbiology for the study of microbial communities in different habitats using molecular analysis, with particular attention to human health related microbes d) plant-fungus interactions, including mycorrhizal associations and endophytic fungi, especially in medicinal plants e) animal associated microbes, gut microbiome analysis.
"I am recruiting PhD, MS students, and Postdoctoral researchers with strong background and interest in my research areas".
Overview of research activities:
Use of innovative substrates for mushrooms cultivation, study of mushrooms medicinal properties, isolation from nature of medicinal fungal species and analysis of their active compounds.
Fungal and bacterial communities in natural environments. Morphological and molecular species identification. Phylogenetics. Analysis of the influence of environmental biotic and abiotic factors on microbial distribution and diversity. Analysis of airborne microbial communities in indoor and outdoor environments, air quality monitoring.
Microbiome analysis on environmental samples. Metagenomics. Fungi from extreme environments, such as volcanic areas, high mountains, and hot springs. Fungal isolation and antibiotic activity.
Orchid mycorrhizal associations. Diversity and functional aspect. Molecular identification of orchid associated fungi. Phylogenetic analysis. Carbon and nitrogen stable isotope abundance analysis for understanding plant-fungus nutrient exchange.
Some examples of research projects performed in Lorenzo Pecoraro's lab:
Analysis of gut-associated fungi from Chinese mitten crab Eriocheir sinensis.
Chinese mitten crab, Eriocheir sinensis (Varunidae), is one of the most popular and widely cultivated freshwater crab species in the Chinese food industry, with high commercial importance and nutri- tional value. We analyzed the diversity of culturable fungi in the gut of E. sinensis collected from a rice-crab co-culture system in Tianjin, China. We isolated 41 fungal strains from the gut of analyzed male and female crabs, using the dilution plate method. Morphological and molecular identifica- tion based on nuclear ribosomal internal transcribed spacer (ITS) sequencing suggested that these isolates belonged to 16 genera in Ascomycota, Basidiomycota, and Mucoromycota. Aspergillus was the dominant identified genus followed by Penicillium and Talaromyces. Yeasts, including Candida, Clavispora, Meyerozyma, and Trichosporon genera, accounted for a significant portion (12.2%) of the isolated strains. Statistical analysis showed significant differences in gut-associated fungal communi- ties between female and male crabs, with female individuals showing a higher species diversity. Our study represents the first report on intestinal fungal communities of Chinese mitten crab, providing valuable microbiological information that could be essential for supporting the effective manage- ment and conservation of this crab species, and for the improvement of the economic performance of the crab industry.
Analysis of culturable airborne fungi in outdoor environments in Tianjin, China.
Fungal spores dispersed in the atmosphere may become cause of different pathological conditions and allergies for human beings. A number of studies have been performed to analyze the diversity of airborne fungi in different environments worldwide, and in particular in many urban areas in China. We investigated, for the first time, the diversity, concentration and distribution of airborne fungi in Tianjin city. We sampled 8 outdoor environments, using open plate method, during a whole winter season. Isolated fungi were identified by morphological and molecular analysis. Environmental factors which could influence the airborne fungi concentration (temperature, humidity, wind speed, and air pressure) were monitored and analyzed. The effect of different urban site functions (busy areas with high traffic flow and commercial activities vs. green areas) on airborne fungal diversity was also analyzed. A total of 560 fungal strains, belonging to 110 species and 49 genera of Ascomycota (80 %), Basidiomycota (18 %), and Mucoromycota (2 %) were isolated in this study. The dominant fungal genus was Alternaria (22 %), followed by Cladosporium (18.4 %), Naganishia (14.1 %), Fusarium (5.9 %), Phoma (4.11 %), and Didymella (4.8 %). A fungal concentration ranging from 0 to 3224.13 CFU m−3 was recorded during the whole study. Permutational multivariate analysis showed that the month was the most influential factor for airborne fungal community structure, probably because it can be regarded as a proxy of environmental variables, followed by wind speed. The two analyzed environments (busy vs. green) had no detectable effect on the air fungal community, which could be related to the relatively small size of parks in Tianjin and/or to the study season. Our study shed light on the highly diverse community of airborne fungi characterizing the outdoor environments of Tianjin, and clarified the role that different environmental factors played in shaping the analyzed fungal community. The dominant presence of fungi with potential hazardous effect on human health, such as Alternaria, Cladosporium and Naganishia, deserves further attention. Our results may represent a valuable source of information for air quality monitoring, microbial pollution control, and airborne diseases prevention.
Analysis of Soil Fungal and Bacterial Communities in Tianchi Volcano Crater, Northeast China.
High-altitude volcanoes, typical examples of extreme environments, are considered of particular interest in biology as a possible source of novel and exclusive microorganisms. We analyzed the crater soil microbial diversity of Tianchi Volcano, northeast China, by combining molecular and morphological analyses of culturable microbes, and metabarcoding based on Illumina sequencing, in order to increase our understanding of high-altitude volcanic microbial community structure. One-hundred and seventeen fungal strains belonging to 51 species and 31 genera of Ascomycota, Basidiomycota and Mucoromycota were isolated. Penicillium, Trichoderma, Cladosporium, Didymella, Alternaria and Fusarium dominated the culturable fungal community. A considerable number of isolated microbes, including filamentous fungi, such as Aureobasidium pullulans and Epicoccum nigrum, yeasts (Leucosporidium creatinivorum), and bacteria (Chryseobacterium lactis and Rhodococcus spp.), typical of high-altitude, cold, and geothermal extreme environments, provided new insights in the ecological characterization of the investigated environment, and may represent a precious source for the isolation of new bioactive compounds. A total of 1254 fungal and 2988 bacterial operational taxonomic units were generated from metabarcoding. Data analyses suggested that the fungal community could be more sensitive to environmental and geographical change compared to the bacterial community, whose network was characterized by more complicated and closer associations.
Molecular evidence supports simultaneous association of the achlorophyllous orchid Chamaegastrodia inverta with ectomycorrhizal Ceratobasidiaceae and Russulaceae
Achlorophyllous orchids are mycoheterotrophic plants, which lack photosynthetic ability and associate with fungi to acquire carbon from different environmental sources. In tropical latitudes, achlorophyllous forest orchids show a preference to establish mycorrhizal relationships with saprotrophic fungi. However, a few of them have been recently found to associate with ectomycorrhizal fungi and there is still much to be learned about the identity of fungi associated with tropical orchids. The present study focused on mycorrhizal diversity in the achlorophyllous orchid C. inverta, an endangered species, which is endemic to southern China. The aim of this work was to identify the main mycorrhizal partners of C. inverta in different plant life stages, by means of morphological and molecular methods. Microscopy showed that the roots of analysed C. inverta samples were extensively colonized by fungal hyphae forming pelotons in root cortical cells. Fungal ITS regions were amplified by polymerase chain reaction, from DNA extracted from fungal mycelia isolated from orchid root samples, as well as from total root DNA. Molecular sequencing and phylogenetic analyses showed that the investigated orchid primarily associated with ectomycorrhizal fungi belonging to a narrow clade within the family Ceratobasidiaceae, which was previously detected in a few fully mycoheterotrophic orchids and was also found to show ectomycorrhizal capability on trees and shrubs. Russulaceae fungal symbionts, showing high similarity with members of the ectomycorrhizal genus Russula, were also identified from the roots of C. inverta, at young seedling stage. Ascomycetous fungi including Chaetomium, Diaporthe, Leptodontidium, and Phomopsis genera, and zygomycetes in the genus Mortierella were obtained from orchid root isolated strains with unclear functional role. This study represents the first assessment of root fungal diversity in the rare, cryptic and narrowly distributed Chinese orchid C. inverta. Our results provide new insights on the spectrum of orchid-fungus symbiosis suggesting an unprecedented mixed association between the studied achlorophyllous forest orchid and ectomycorrhizal fungi belonging to Ceratobasidiaceae and Russulaceae. Ceratobasidioid fungi as dominant associates in the roots of C. inverta represent a new record of the rare association between the identified fungal group and fully mycoheterotrophic orchids in nature.
Plant Growth Promoting Rhizobacteria, Arbuscular Mycorrhizal Fungi and Their Synergistic Interactions to Counteract the Negative Effects of Saline Soil on Agriculture: Key Macromolecules and Mechanisms.
Soil saltiness is a noteworthy issue as it results in loss of profitability and development of agrarian harvests and decline in soil health. Microorganisms associated with plants contribute to their growth promotion and salinity tolerance by employing a multitude of macromolecules and pathways. Plant growth promoting rhizobacteria (PGPR) have an immediate impact on improving profitability based on higher crop yield. Some PGPR produce 1-aminocyclopropane-1-carboxylic (ACC) deaminase (EC 4.1.99.4), which controls ethylene production by diverting ACC into α-ketobutyrate and ammonia. ACC deaminase enhances germination rate and growth parameters of root and shoot in different harvests with and without salt stress. Arbuscular mycorrhizal fungi (AMF) show a symbiotic relationship with plants, which helps in efficient uptake of mineral nutrients and water by the plants and also provide protection to the plants against pathogens and various abiotic stresses. The dual inoculation of PGPR and AMF enhances nutrient uptake and productivity of several crops compared to a single inoculation in both normal and stressed environments. Positively interacting PGPR + AMF combination is an efficient and cost-effective recipe for improving plant tolerance against salinity stress, which can be an extremely useful approach for sustainable agriculture.
Figure. PGPR-mediated salt tolerance by multiple rhizospheric interactions in soil. (1) Release of plant growth regulators to improve nutrition uptake. (2) Production of antioxidant enzymes. (3) Maintenance of ionic homeostasis via transporters. (4) Increased water uptake by improving permeability and soil aggregation through EPS production. (5) Production of osmolytes such as proline and glycine that act as osmoprotectants. (6) Inhibition of ethylene production to reduce stress levels in the plant.
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
The research in the group of Sun involves investigation of B cell development and B cell related diseases. In recent years, immunotherapies with antibodies to depleting B cells are widely used in autoimmune diseases and B cell lymphoma. The strategy in this group is to design cytokine antagonist peptides using computer-aided design, fuse the peptides with human IgG Fc to form peptibodies by gene engineering, and analyze their activity in vitro and in vivo. Several peptibodies inhibiting B lymphocyte stimulator (BLyS), a critical factor for B cell maturation and survival, are currently tested in cell culture and SLE animal models in this lab. Because overexpression of BLyS is involved in pathogenesis and development of autoimmune diseases and B cell malignances, the BLyS antagonists designed and analyzed may be potential therapeutic reagents for these diseases.
The Zhang lab identifies and characterizes new enzymes and new metabolic pathways in nature using a combination of bioinformatics, genetic, biochemical and biophysical methods. In particular, the Zhang lab has a long term interest in metal trafficking, metalloenzymes. and their catalytic mechanisms. Other projects in the Zhang lab include synthetic biology, and immuno-based human disease diagnosis.
For more information about the Zhang Lab, please visit
Expression and regulation of important enzymes in some metabolic pathways in microorganisms.
The research in the group of ZHANG focuses on two areas: 1) Mechanisms of transcriptional regulation involved in cancer，oxidative stress response and a variety of health disorders by means of molecular biology method, 2) Mechanism study on interaction of host factors with retroelements and HIV-1 such as helicases, interferon-stimulate genes and RNA binding proteins etc.
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。
Microbiology & Immunology platform focus on the microbiology & immunobiology issues to support the theoretical and methodological research on key pathogenic microorganisms and their pathogenesis and immune mechanisms, and to develop the bio-products (diagnosis reagents, vaccine, adjuvants, therapeutic drug and others) to control infectious diseases. The integrated M & I analysis platform will be constructed to support the life science research and to service the human health in the future.
Research fields:
1.Infection immunity: Structural and functions of viral genomes；Pathogenesis, innate immunity and immune evasion mechanisms of viral infections.
2.Microbial biology in human, animal, food, water and stress environments by epigenetics, comparative genomics and bioinformatics.
3.Regulation and adaptive evolution of key innate immune system during in different biological evolution. Enzymology of immune cells in viral infection and inflammation.
4.Sensing of MAMPs from bacteria, fungi, and viruses or DAMPs by immune PRRs and their compartments. Immune regulation roles of natural adjuvants (microbiota, natural components of commensal lactic acid bacteria, plants) or synthetic agonists on innate immunity.
5.Enzymology of immune cells in viral infection and inflammation. General scheme for the enrichment of microbial cells or biomarkers with affinity probes showed as following figure.
Innate immunity is the first line of host defense against invading pathogenic microorganisms, where type I interferon (IFN) production is initiated at the early stages and subsequently induces the expression of IFN-stimulated genes (ISGs) in an autocrine and paracrine manner, leading to the destruction of invading pathogens. In order to replicate and survive, viruses have evolved diverse strategies to evade IFN responses. One area of research in my laboratory is to understand the molecular mechanisms of evasion of innate immunity by pathogenic microorganisms.
Another goal of our research is to study the molecular mechanisms of severe fever with thrombocytopenia syndrome virus (SFTSV) and enteroviruss D68 pathogenesis.
Key scientific issues
1) Innate detection of viral pathogenic microorganisms;
2) The mechanism of ubiquitin in the antiviral signaling pathway;
3) The molecular mechanism of the generation and regulation of type I interferon and other important cytokines by natural immune activation;
4) The mechanism of cytokine secretion after natural immune activation;
l.Molecular mechanisms on pathogenesis and immunity of viruses and bacterial toxins.
2.The roles of cell-intrinsic restriction and recognition in innate immunity and inflammatory disease of viral infection.
3.Development the techniques for diagnosis and prevention of human and animal pathogenic microorganisms and their toxic products in food, water, and environment.
4.Functional genomics and engineering of resource microbes to promote human health.
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.
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 in the Chung group focuses on understanding the role of microglia in neuroinflammation. Inflammation is a key component of pathophysiology of both acute injuries and chronic diseases including Parkinson’s and Alzheimer’s. Microglia activation/chemotaxis is prerequisite for microglia function whether neuroprotective or inflammatory, making understanding essential for design of rational approaches for therapeutic modulation and regulation of microglia proliferation and chemotaxis. Emphasis is on control of activation/chemotaxis of resident microglia in the brain in early stages of neuroinflammation. Unraveling complex networks of signaling downstream of P2Y12 receptor during microglia chemotaxis is an important target. Elucidation of neurotoxic effects of microglia observed in depression is another area of research interests.
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.
Cytochrome P450 (CYP) monooxygenases, the nature’s most versatile biological catalysts have unique ability to catalyse regio-, chemo-, and stereospecific oxidation of a wide range of substrates under mild reaction conditions, thereby addressing a significant challenge in chemocatalysis. In the recent decades, the importance of CYPs is illustrated by the fact that they are responsible for the majority of Phase I reactions in human drug metabolism, and their substrates include a broad range of active pharmaceutical ingredients, environmental toxins, carcinogens, and food-derived chemicals. Therefore, a compilation of CYP monooxygenases is required for a rational comprehensive approach for elucidating the catalytic potentials and functional utilities of human CYPs for industrial approach. This urged us to generate the gene library of human cytochrome P450s to facilitate the glimpse of molecular mechanisms and metabolic diversity of P450s, thereby functionally explore and characterize the novel enzymes. Here I have listed the three major ongoing projects which I am currently engaged in Prof. Bureik's laboratory.
1. Construction of Human CYP Gene Library
2. Functional Expression of Human CYPs in Fission Yeast Reconstituted System
3. Systematic assessment of CYP-dependent metabolism with Differential Redox partners
The research of the Gao group covers medicinal chemistry and molecular targeting, synthetic chemistry and organo catalysis, and computer-aided drug design, aimed at the discovery of functional drug delivery carriers and understanding mechanisms of molecular targeting. Specific areas include a) strategies for development of small molecular anti-cancer drugs for targeted therapy, b) design and development of actively transportable small molecule drugs or protein-drug conjugates, c) discovery and development of novel drug-delivery carriers and pharmaceutics based on supramolecular chemistry, d) computer aided molecular design and modeling for innovative drug discovery and mechanistic study of drug transporters.
MICROBIAL BIOTECHNOLOGY
NANOBIOTECHNOLOGY
Identification and characterization of new enzymes and new metabolic pathways in nature using a combination of bioinformatics, genetic, biochemical and biophysical methods.
We are interested in understanding the DNA repair mechanism in the germline. Especially, we have focused on investigating the epigenetic regulation of DNA damage response and repair. We use a microscopic size nematode C. elegans and mammalian cells to study epigenetic control of DNA repair mechanism. 1. The role of conserved Epigenetic regulators in DNA repair and damage response. 2.The role of novel and conserved gene of DNA repair and damage response.
We are recuiting hard working students. Post-doc or Students interested in working in Genetics or Molecular biology in my lab, send an E-mail to hm.k @ duke.edu
1998年-2001年在天津泌尿外科研究所畅继武教授课题组所做的课题为肿瘤热休克蛋白90-肽复合物的提取纯化，并用该复合物诱导T细胞转化为特异性细胞毒性T淋巴细胞，为肿瘤的生物治疗进行基础研究。2001年继续以肿瘤特异性CTL为核心以树突状细胞转化特异性CTL为方法，进行治疗肿瘤的基础及临床应用的研究，该研究获得天津市科学技术进步奖二等奖。
Paramagnetic NMR, Pseudocontact Shifts, MS Spectrometry.
Our laboratory is interested in the cellular innate immune events that sense viral infection and inhibit viral replication.
We are particularly focusing on the following two aspects: (1) endogenous suppressors that modulate innate immune signaling, and (2) molecular mechanism of autoimmune disorders caused by aberrant immune responses.
Lorenzo Pecoraro research group interests mainly focus on a) fungal and bacterial biotechnology, bioremediation, medicinal mushrooms b) microbial taxonomy and community ecology, network analysis c) environmental microbiology for the study of microbial communities in different habitats using molecular analysis, with particular attention to human health related microbes d) plant-fungus interactions, including mycorrhizal associations and endophytic fungi, especially in medicinal plants e) animal associated microbes, gut microbiome analysis.
"I am recruiting PhD, MS students, and Postdoctoral researchers with strong background and interest in my research areas".
Overview of research activities:
Use of innovative substrates for mushrooms cultivation, study of mushrooms medicinal properties, isolation from nature of medicinal fungal species and analysis of their active compounds.
Fungal and bacterial communities in natural environments. Morphological and molecular species identification. Phylogenetics. Analysis of the influence of environmental biotic and abiotic factors on microbial distribution and diversity. Analysis of airborne microbial communities in indoor and outdoor environments, air quality monitoring.
Microbiome analysis on environmental samples. Metagenomics. Fungi from extreme environments, such as volcanic areas, high mountains, and hot springs. Fungal isolation and antibiotic activity.
Orchid mycorrhizal associations. Diversity and functional aspect. Molecular identification of orchid associated fungi. Phylogenetic analysis. Carbon and nitrogen stable isotope abundance analysis for understanding plant-fungus nutrient exchange.
Some examples of research projects performed in Lorenzo Pecoraro's lab:
Analysis of gut-associated fungi from Chinese mitten crab Eriocheir sinensis.
Chinese mitten crab, Eriocheir sinensis (Varunidae), is one of the most popular and widely cultivated freshwater crab species in the Chinese food industry, with high commercial importance and nutri- tional value. We analyzed the diversity of culturable fungi in the gut of E. sinensis collected from a rice-crab co-culture system in Tianjin, China. We isolated 41 fungal strains from the gut of analyzed male and female crabs, using the dilution plate method. Morphological and molecular identifica- tion based on nuclear ribosomal internal transcribed spacer (ITS) sequencing suggested that these isolates belonged to 16 genera in Ascomycota, Basidiomycota, and Mucoromycota. Aspergillus was the dominant identified genus followed by Penicillium and Talaromyces. Yeasts, including Candida, Clavispora, Meyerozyma, and Trichosporon genera, accounted for a significant portion (12.2%) of the isolated strains. Statistical analysis showed significant differences in gut-associated fungal communi- ties between female and male crabs, with female individuals showing a higher species diversity. Our study represents the first report on intestinal fungal communities of Chinese mitten crab, providing valuable microbiological information that could be essential for supporting the effective manage- ment and conservation of this crab species, and for the improvement of the economic performance of the crab industry.
Analysis of culturable airborne fungi in outdoor environments in Tianjin, China.
Fungal spores dispersed in the atmosphere may become cause of different pathological conditions and allergies for human beings. A number of studies have been performed to analyze the diversity of airborne fungi in different environments worldwide, and in particular in many urban areas in China. We investigated, for the first time, the diversity, concentration and distribution of airborne fungi in Tianjin city. We sampled 8 outdoor environments, using open plate method, during a whole winter season. Isolated fungi were identified by morphological and molecular analysis. Environmental factors which could influence the airborne fungi concentration (temperature, humidity, wind speed, and air pressure) were monitored and analyzed. The effect of different urban site functions (busy areas with high traffic flow and commercial activities vs. green areas) on airborne fungal diversity was also analyzed. A total of 560 fungal strains, belonging to 110 species and 49 genera of Ascomycota (80 %), Basidiomycota (18 %), and Mucoromycota (2 %) were isolated in this study. The dominant fungal genus was Alternaria (22 %), followed by Cladosporium (18.4 %), Naganishia (14.1 %), Fusarium (5.9 %), Phoma (4.11 %), and Didymella (4.8 %). A fungal concentration ranging from 0 to 3224.13 CFU m−3 was recorded during the whole study. Permutational multivariate analysis showed that the month was the most influential factor for airborne fungal community structure, probably because it can be regarded as a proxy of environmental variables, followed by wind speed. The two analyzed environments (busy vs. green) had no detectable effect on the air fungal community, which could be related to the relatively small size of parks in Tianjin and/or to the study season. Our study shed light on the highly diverse community of airborne fungi characterizing the outdoor environments of Tianjin, and clarified the role that different environmental factors played in shaping the analyzed fungal community. The dominant presence of fungi with potential hazardous effect on human health, such as Alternaria, Cladosporium and Naganishia, deserves further attention. Our results may represent a valuable source of information for air quality monitoring, microbial pollution control, and airborne diseases prevention.
Analysis of Soil Fungal and Bacterial Communities in Tianchi Volcano Crater, Northeast China.
High-altitude volcanoes, typical examples of extreme environments, are considered of particular interest in biology as a possible source of novel and exclusive microorganisms. We analyzed the crater soil microbial diversity of Tianchi Volcano, northeast China, by combining molecular and morphological analyses of culturable microbes, and metabarcoding based on Illumina sequencing, in order to increase our understanding of high-altitude volcanic microbial community structure. One-hundred and seventeen fungal strains belonging to 51 species and 31 genera of Ascomycota, Basidiomycota and Mucoromycota were isolated. Penicillium, Trichoderma, Cladosporium, Didymella, Alternaria and Fusarium dominated the culturable fungal community. A considerable number of isolated microbes, including filamentous fungi, such as Aureobasidium pullulans and Epicoccum nigrum, yeasts (Leucosporidium creatinivorum), and bacteria (Chryseobacterium lactis and Rhodococcus spp.), typical of high-altitude, cold, and geothermal extreme environments, provided new insights in the ecological characterization of the investigated environment, and may represent a precious source for the isolation of new bioactive compounds. A total of 1254 fungal and 2988 bacterial operational taxonomic units were generated from metabarcoding. Data analyses suggested that the fungal community could be more sensitive to environmental and geographical change compared to the bacterial community, whose network was characterized by more complicated and closer associations.
Molecular evidence supports simultaneous association of the achlorophyllous orchid Chamaegastrodia inverta with ectomycorrhizal Ceratobasidiaceae and Russulaceae
Achlorophyllous orchids are mycoheterotrophic plants, which lack photosynthetic ability and associate with fungi to acquire carbon from different environmental sources. In tropical latitudes, achlorophyllous forest orchids show a preference to establish mycorrhizal relationships with saprotrophic fungi. However, a few of them have been recently found to associate with ectomycorrhizal fungi and there is still much to be learned about the identity of fungi associated with tropical orchids. The present study focused on mycorrhizal diversity in the achlorophyllous orchid C. inverta, an endangered species, which is endemic to southern China. The aim of this work was to identify the main mycorrhizal partners of C. inverta in different plant life stages, by means of morphological and molecular methods. Microscopy showed that the roots of analysed C. inverta samples were extensively colonized by fungal hyphae forming pelotons in root cortical cells. Fungal ITS regions were amplified by polymerase chain reaction, from DNA extracted from fungal mycelia isolated from orchid root samples, as well as from total root DNA. Molecular sequencing and phylogenetic analyses showed that the investigated orchid primarily associated with ectomycorrhizal fungi belonging to a narrow clade within the family Ceratobasidiaceae, which was previously detected in a few fully mycoheterotrophic orchids and was also found to show ectomycorrhizal capability on trees and shrubs. Russulaceae fungal symbionts, showing high similarity with members of the ectomycorrhizal genus Russula, were also identified from the roots of C. inverta, at young seedling stage. Ascomycetous fungi including Chaetomium, Diaporthe, Leptodontidium, and Phomopsis genera, and zygomycetes in the genus Mortierella were obtained from orchid root isolated strains with unclear functional role. This study represents the first assessment of root fungal diversity in the rare, cryptic and narrowly distributed Chinese orchid C. inverta. Our results provide new insights on the spectrum of orchid-fungus symbiosis suggesting an unprecedented mixed association between the studied achlorophyllous forest orchid and ectomycorrhizal fungi belonging to Ceratobasidiaceae and Russulaceae. Ceratobasidioid fungi as dominant associates in the roots of C. inverta represent a new record of the rare association between the identified fungal group and fully mycoheterotrophic orchids in nature.
Plant Growth Promoting Rhizobacteria, Arbuscular Mycorrhizal Fungi and Their Synergistic Interactions to Counteract the Negative Effects of Saline Soil on Agriculture: Key Macromolecules and Mechanisms.
Soil saltiness is a noteworthy issue as it results in loss of profitability and development of agrarian harvests and decline in soil health. Microorganisms associated with plants contribute to their growth promotion and salinity tolerance by employing a multitude of macromolecules and pathways. Plant growth promoting rhizobacteria (PGPR) have an immediate impact on improving profitability based on higher crop yield. Some PGPR produce 1-aminocyclopropane-1-carboxylic (ACC) deaminase (EC 4.1.99.4), which controls ethylene production by diverting ACC into α-ketobutyrate and ammonia. ACC deaminase enhances germination rate and growth parameters of root and shoot in different harvests with and without salt stress. Arbuscular mycorrhizal fungi (AMF) show a symbiotic relationship with plants, which helps in efficient uptake of mineral nutrients and water by the plants and also provide protection to the plants against pathogens and various abiotic stresses. The dual inoculation of PGPR and AMF enhances nutrient uptake and productivity of several crops compared to a single inoculation in both normal and stressed environments. Positively interacting PGPR + AMF combination is an efficient and cost-effective recipe for improving plant tolerance against salinity stress, which can be an extremely useful approach for sustainable agriculture.
Figure. PGPR-mediated salt tolerance by multiple rhizospheric interactions in soil. (1) Release of plant growth regulators to improve nutrition uptake. (2) Production of antioxidant enzymes. (3) Maintenance of ionic homeostasis via transporters. (4) Increased water uptake by improving permeability and soil aggregation through EPS production. (5) Production of osmolytes such as proline and glycine that act as osmoprotectants. (6) Inhibition of ethylene production to reduce stress levels in the plant.
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
The research in the group of Sun involves investigation of B cell development and B cell related diseases. In recent years, immunotherapies with antibodies to depleting B cells are widely used in autoimmune diseases and B cell lymphoma. The strategy in this group is to design cytokine antagonist peptides using computer-aided design, fuse the peptides with human IgG Fc to form peptibodies by gene engineering, and analyze their activity in vitro and in vivo. Several peptibodies inhibiting B lymphocyte stimulator (BLyS), a critical factor for B cell maturation and survival, are currently tested in cell culture and SLE animal models in this lab. Because overexpression of BLyS is involved in pathogenesis and development of autoimmune diseases and B cell malignances, the BLyS antagonists designed and analyzed may be potential therapeutic reagents for these diseases.
The Zhang lab identifies and characterizes new enzymes and new metabolic pathways in nature using a combination of bioinformatics, genetic, biochemical and biophysical methods. In particular, the Zhang lab has a long term interest in metal trafficking, metalloenzymes. and their catalytic mechanisms. Other projects in the Zhang lab include synthetic biology, and immuno-based human disease diagnosis.
For more information about the Zhang Lab, please visit
Expression and regulation of important enzymes in some metabolic pathways in microorganisms.
The research in the group of ZHANG focuses on two areas: 1) Mechanisms of transcriptional regulation involved in cancer，oxidative stress response and a variety of health disorders by means of molecular biology method, 2) Mechanism study on interaction of host factors with retroelements and HIV-1 such as helicases, interferon-stimulate genes and RNA binding proteins etc.
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。
