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.

无内容

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 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.

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.

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

1. MICROBIAL BIOTECHNOLOGY

2. NANOBIOTECHNOLOGY
   

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

(1) Cancer Immunoengineering

(2) Non-viral Delivery of Nucleic Acid Drugs

(3) Live Cell Mediated Drug Delivery

The main interest is focused on structural and functional studies of biologically and medically important macromolecules, mainly through protein crystallography, in couple with biochemical, cell biology and other approaches, to gain insights into structure-function relationship of these macromolecules.

We are interested in the structural and mechanistic basis of developmental signaling that are important in stem cell biology, cancer metastasis, and regenerative medicine. At structural levels, we want to understand: how developmental signaling molecules are regulated by extracellular micro-environment, how these molecules are recognized by cell surface receptors, and how these molecules are engaged with intracellular signaling cascades through lipid bilayer. At functional levels, we focus on understanding how ligand isoforms are distinguished by their targeted cells to generate distinct cellular outcomes, and how developmental signaling is involved in stem cell self-renewal and differentiation. Eventually, we want to explore potentials in therapeutic development against cancer and other human diseases.

Research Interest: Osteoimmunology, bone biology, osteoporosis, tissue engeneering (bone and cartilage regeneration)

My research is mainly focus on to unravle the mechanism of systemic inflammation-induced osteoporosis. 

Fig: Mechanism of inflammation-induced osteoporosis

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

Fractionation and Screening of Tinospora cordifolia plant extracts and Bioassay for Anti-diabetic activity in the rodent animal model

Studies on inhibition of Human serum Paraoxonase: Effect of physiological and environmental toxic molecules. 

The research in the group of Wang involves research and development related to drug advancements and medicinal chemistry, including cardiovascular drugs, anti asthmatic drugs, anti-tumor drugs, anti-virus drugs, anti inflammatory and anti-bacteria drugs, anti-diabetes drugs, benzodiazepine-type hypnotic drugs, non-patented drug development and industrialization.  Synthesis of natural products and their structural modification is carried out in this group.

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

The research in the Woycechowsky group focuses on the supramolecular chemistry of proteins. In particular, we are interested in proteins that assemble into symmetrical, closed-shell, polyhedral capsid structures. Protein capsids can act as molecular containers and delivery vehicles for a variety of molecular cargoes, and therefore are useful for bionanotechnological applications, such as drug delivery, catalysis, and materials synthesis. Protein engineering strategies are used to explore and exploit the supramolecular chemistry of protein capsids. This approach is inherently interdisciplinary, utilizing methods from biochemistry, biophysics, molecular biology, organic chemistry, and cell biology. Research projects in our lab fall into three main areas, including 1) capsid self-assembly, 2) molecular encapsulation, and 3) drug delivery.

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

http://zhangyanlab.org 

Include 1 or 2 small representative pictures of good quality

Research in the Yan lab focuses on structure biology of protein or protein complex with significant biology function, particularly on structure and function of those important membrane proteins, such as photosynthetic membrane proteins, intramembrane proteases, membrane transporters, ion channels and cancer-related viral membrane proteins, etc.

The Cartoon below shows substrate transport across membrane by transporter protein.

The qualitative and quantitative analysis of complex system based on HRMS

The research in the group of Zhang is encompassed in the areas of chiral separation and proteomics analysis.

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。