Application of Nanobiomaterials and Nanobiotechnology in the Diagnosis and Treatment of Some Major Diseases, Such as Cancer, Alzheimer’s disease, Heart disease, Infectious Diseases and etc.

Quantum dots based POCT test strip and reader for tumor markers . Targeting effect of multi-functional nanoprobe  in brest cancer and glioma of rats

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.

Dr. Chen focuses on exploring the functions of critical replicase proteins involved in the pathogenesis of life-threatening pathogens (Cytomegalovirus, Coronaviruses and Enterovirus 71, etc.) employing the structural biology approaches. He also performs structure-based inhibitor design, aiming at developing effective antiviral lead compounds. As shown below, Fig. 1 illustrates the crystal structure of Enterovirus 71 RNA-dependent RNA polymerase in complex with its primer precursor peptide VPg. Fig. 2 depicts the structure of feline infectious peritonitis virus main protease in complex with a structure-based inhibitor N3.

Figure 1. Crystal structure of Enterovirus 71 (EV71) RNA-dependent RNA polymerase (3D) in complex with its primer precursor peptide VPg (PDB entry 4IKA) and alignment with the structure of Cosackievirus B3 (CVB3) 3D-VPg complex (PDB entry 3CDW) and Poliovirus apo 3D (PDB entry 1RDR).

Figure 2. Crystal structure of feline infectious peritonitis virus main protease in complex with a structure-based inhibitor N3 (PDB entry 5EU8).

(1) Research on the catalytic activity of nanomaterials including metal nanoparticles, metal nanoclusters, graphene oxide, carbon dots, quantum dots, molybdenum disulfide, etc on chemiluminescent reations.

(2) Develop novel chemiluminescent immunoassay, sequence-specific DNA detection method, protease activity assay, and small molecules sensing method based on the unique properties of those nanomaterials.

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.

The preparation of biomelcular detection platform for desease diagnosis

1.Preparation of the quantum dot nanobeads-based immunochromatography test strip for the  high sensitive and quantitative detection different cancer biomarkers.

2.The fabrication of Microfluidic Protein Chip based on the quantum dots encoding microbeads for multimoleculars detection 

The preparation of mucus-penetrating nanoparticles for drug delivery to mucosal tissues

3.Preparation of magnetic mucus-penetrating nanoparticles for vaginal drug delivery.

4.The study of mucus-penetrating nanoparticles penetrating human cystic fibrosis sputum and controlling inflammation in a murine model of lung inflammation.

The research my group lies at the interaction of virus and host proteins, such as the interaction of accessory protein of HIV-1,HIV-2 and SIV with host protein of E3 ligase,SAMHD1 and so on, another study is about molecular epidemiology of virus, including Enterovirus 71A and Coxsackievirus A16.

1.A novel motif  in Vpx and Vpr of HIV/SIV was identified which is critical for Vpx-mediated degradation of nuclear SAMHD1 and Vpr-induced G2 arrest.

2.In the study of circulating HFMD-Associated Coxsackievirus A16, we found that it is genetically and phenotypically distinct from the prototype CV-A16.

3.Map the founction region of host protein SAMHD1 which is critical for nuclear localization and Vpx-Mediated degradation.

1. Molecular mechanism of plant stomatal movement under drought stress

Focused on signal transduction in plant hormone abscisic acid (ABA) regulates stomatal movement under drought stress, and biological function of the protein kinase GHR1 in Arabidopsis. Plant physiology and molecular techniques were used to study the phenotype of the ghr1 mutant. The results showed a new protein kinase GHR1 that interacts with, phosphorylates, and regulates slow anion channel associated1 (SLAC1). We also uncover GHR1 is negatively regulated by ABA Insensitive2 (ABI2) but not by ABI1.

2. Design molecular markers for assisted breeding of melon.

From melon transcriptome sequencing, find information and design molecular markers (SSR and SNP) for melon molecular assisted breeding.

The research of the Huang group encompasses the following main areas:  

1) Molecular design (AIDD & Chiral Catalyst/ligand Design)

3) New Chemical Space Exploration

1 Plant Molecular Biology: Phosphate signaling pathway

2 Bioinformatics:

Nan Li is working in the field of nanomedicine to develop various functional nanomaterials and nanotechnologies for cancer diagnosis and therapy, particular for phototherapy and photodynamic therapy of cancer.

(1) Cancer Immunoengineering

(2) Non-viral Delivery of Nucleic Acid Drugs

(3) Live Cell Mediated Drug Delivery

1. Bioengineering of spider fibroins

Spider silks are proteinaceous biopolymers with extraordinary physical properties and biomimetic potential. This research focuses on the structure-based engineering and design of silk fibroins for the production of artificial spider silks with desirable mechanical properties.

2. NMR structural & functional studies on p75NTR signaling

p75 neurotrophin receptor (p75NTR) is a member of the Tumor Necreosis Factor Superfamily and its signaling actively contributes to neurodegeneration. The aim of this project is to elucidate structural mechanisms of p75NTR signaling in the nervous system and to discover drugs for neurodegenerative diseases and nerve injury. 

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.

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.

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

Investigation of interaction between small molecule and protein

The binding mechanism such as binding constant, binding distance, thermodynamic parameter and conformational change of protein is studied.

Explore the effects of macromolecular crowding on protein properties using various spectroscopic approaches and nonlinear science fractal theory.

1. Structural insight into properties of protoporphyrinogen oxidases

    Determined the structures of Bacillus subtilis and human PPOs\

2. Determined the structures of SAMHD1

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.

My research is focused on two specific areas, one is hydrophobin and another one is biology and disease of urothelium. For the hydrophobin study, my research is involved but not limited to: 1) Study protein-protein interaction and protein assembly in vitro and in vivo. 2) Protein expression, purification and characterization in both prokaryotic and eukaryotic systems.  3) Hydrophobin based drug and gene delivery systems. 4) Hydrophobin based chip and sensors. 5) Antibody production and purification. 6) Large-scale high-density fermentation and downstream separation. For the urothelium study, my research is involved but not limited to: 1) Study the urothelial disease like bacterial urinary tract infection and bladder. 2) study of ATP release channel of urothelium in mouse model. 3) Drug release and delivery by adenovirus and liposome in urothelium. 4) Characterization and function study of lipid raft proteins. 5) Study the stem cell of the urothelium.

Developing innovative methods of nanomaterials synthesis and fabrication techniques for directed assembly of multi-functional nanocomplex from polymers, mental naoparticles and organic-inorganic hybrids.

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.

Investigate interactions between innate immunity and Hepatitis B virus infection

Probing the mechanism of how innate immune cells (eg: gd T cells) affected by HBV infectious environment as well as roles of innate immune cells in diseases progression

Use different type of nanoparticles as vector, explore new way in diagnosis and treatment of liver fibrosis and hepatocarcinoma.

Crystal structures of protein complexes in the areas of innate immune response and DNA repair.

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 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.

Human long interspersed elements 1 (LINE-1 or L1) is the only autonomous non-LTR retroelement in humans and has been associated with genome instability, inherited genetic diseases, and the development of cancer.  Certain human APOBEC3 family proteins are known to have LINE-1 restriction activity.  Our group focuses on exploring the mechanisms of APOBEC3 family proteins on LINE-1 restriction.  Some of A3 proteins interact with LINE-1 ORF1p to target LINE-1 ribonucleoprotein particles in an RNA-dependent manner and further Inhibit the LINE-1 reverse transcriptase activity. 

Figure Inhibitory effect of A3B and A3DE on LINE-1 mobility. The A3B- or A3DE-expressing vector was co-transfected with L1_RP-EGFP, and flow cytometry was used to detect the EGFP-positive cells. Representative flow cytometry dot diagrams for A3B and A3DE in LINE-1 restriction. The percentage of EGFP-positive events is shown in the upper right corner of each panel.

Extracellular nucleotides, such as uridine 5'-triphosphate (UTP) and adenosine 5'- triphosphate (ATP), were previously reported to induce contraction of gastric smooth muscle (SM). A dinucleotide uridine adenosine tetraphosphate (Up4A) is a newly identified endothelium-derived contraction factor (EDCF), and induces contraction in vascular SM. It was not tested whether Up4A also induces contraction of gastric SM. Our hypothesis was that Up4A induces contractions of gastric SM, which may differ in circular and longitudinal muscle (CM and LM, respectively). CM and LM were isolated from rat gastric fundus for the measurement of isometric tension using tissue bioassay. Addition of Up4A to tissue bath induced transient contractile responses in both CM and LM, which were similar to those induced by ATP and UTP. In CM, the ranks of potencies and efficacies were UTP > Up4A > ATP. In LM, however, Up4A was much more potent than UTP and ATP. P2X1,2,4,5,7 and P2Y1,2,4,6 receptors were detected in gastric SM using RT-PCR. Up4A failed to induce any contraction in either LM or CM in the absence of extracellular Ca2+ or in the presence of nimodipine, an inhibitor of voltage-dependent Ca²⁺ channel. IP5I (5 μM), a P2X antagonist, did not attenuate Up4A-induced contractions in both LM and CM, but suramin (5 μM), a P2Y receptor antagonist, significantly inhibited Up4A contraction in CM, but not in LM. Up4A contraction in CM, but not in LM, was also inhibited by pretreatment with indomethacin (100 nM), a cyclooxygenase inhibitor, Y-27632 (500 nM), an inhibitor for Rho-activated kinase (ROCK). Therefore, we conclude that Up4A induces extracellular Ca²⁺-dependent contractions in rat gastric LM and CM, and Up4A contraction in CM is through suramin-sensitive P2Y receptor and subsequent activation of the cyclooxygenase and ROCK pathways. 

Effects of Y-27632 on Up4A-induced contractions of CM and LM preparations. (*p < 0.01, n=5).

1. Cadmium-induced activation of HOG and CWI pathway through its upstream elements in budding yeast.

2. Two membrane transporters involved in cadmium stress were regulated by MAPKs pathway.

The research in the group of Zhao encompasses four main areas, including (1) Stimuli-responsive drug delivery systems; (2) Ferroptosis-targeting nanomedicines; (3) Photo-triggered microtubule inhibitors; (4) Pharmaceutical micelles, biomaterials and nanomaterials.

(1) Development of novel phototherapy molecules for disease treatment

(2) Develop new biological probes to assist disease diagnosis and biological mechanism research