A5022156448- Bacteriophages and microbial interactions
- Influenza Virus Research Studies
- RNA and protein synthesis mechanisms
- Plant Virus Research Studies
- Nanoparticle-Based Drug Delivery
- Advanced Electron Microscopy Techniques and Applications
- Transgenic Plants and Applications
- Virus-based gene therapy research
- Microfluidic and Bio-sensing Technologies
- Animal Virus Infections Studies
- Cytomegalovirus and herpesvirus research
- Respiratory viral infections research
- Immunotherapy and Immune Responses
- Herpesvirus Infections and Treatments
- SARS-CoV-2 and COVID-19 Research
- RNA Interference and Gene Delivery
- interferon and immune responses
- Escherichia coli research studies
- Virology and Viral Diseases
- Advanced Drug Delivery Systems
- Characterization and Applications of Magnetic Nanoparticles
- Nanocluster Synthesis and Applications
- Viral Infections and Immunology Research
- Biosensors and Analytical Detection
- Protein Interaction Studies and Fluorescence Analysis
National Institute of Allergy and Infectious Diseases
2018-2023
National Institutes of Health
2018-2023
Case Western Reserve University
2014-2019
University School
2015
Platform technologies based on plant virus nanoparticles (VNPs) and virus-like particles (VLPs) are attracting the attention of researchers clinicians because biocompatible, biodegradable, noninfectious in mammals, can readily be chemically genetically engineered to carry imaging agents drugs. When Physalis mottle (PhMV) coat protein is expressed Escherichia coli, resulting VLPs nearly identical viruses formed vivo. Here, we isolated PhMV-derived from ClearColi cells carried out external...
Molecular imaging approaches and targeted drug delivery hold promise for earlier detection of diseases treatment with higher efficacy while reducing side effects, therefore increasing survival rates quality life. Virus-based nanoparticles are a promising platform because their scaffold can be manipulated both genetically chemically to simultaneously display targeting ligands carrying payloads diagnosis or therapeutic intervention. Here, we displayed 12-amino-acid peptide ligand, GE11...
Nanoparticle camouflage with serum albumin is formulation specific, does not produce antibodies against the coating, and shields nanoparticle antibody recognition.
Abstract Negative‐stain transmission electron microscopy (EM) is a technique that has provided nanometer resolution images of macromolecules for about 60 years. Developments in cryo‐EM image processing have maximized the information gained from averaging large numbers particles. These developments can now be applied back to negative‐stain analysis ascertain domain level molecular structure (10 20 Å) more quickly and efficiently than possible by atomic cryo‐EM. Using uranyl acetate stained...
Shaping contrast agents for macrophage imaging.
Abstract Influenza virus continues to be a major health problem due the continually changing immunodominant head regions of surface glycoprotein, hemagglutinin (HA). However, some emerging vaccine platforms designed by biotechnology efforts, such as recombinant influenza virus-like particles (VLPs) have been shown elicit protective antibodies antigenically different viruses. Here, using biochemical analyses and cryo-electron microscopy methods coupled image analysis, we report composition 3D...
Abstract The 2014 Ebola epidemic is the largest to date. There no cure or treatment for this deadly disease; therefore there an urgent need develop new diagnostics accurately detect Ebola. Current RT-PCR assays lack sensitive and reliable positive controls. To address critical need, we devised a bio-inspired control use in diagnostics: encapsulated scrambled RNA sequences inside of tobacco mosaic virus create biomimicry that non-infectious, but stable could serve as diagnostic assays. Here,...
Nanoparticles offer great potential in drug delivery and imaging, but shielding strategies are necessary to increase circulation time performance. Structure-function studies required define the design rules achieve effective shielding. With several formulations reaching clinical testing approval, ability assess detail nanoparticle at single particle level is becoming increasingly important. To address this need, we use cryo-electron tomography (cryo-ET) investigate stealth-coated...
Abstract Immunoelectron microscopy is a powerful technique for identifying viral antigens and determining their structural localization organization within vaccines viruses. While traditional negative staining transmission electron provides information, identity of components sample may be confounding. allows identification visualization relative positions particulate sample. This simple qualitative analysis samples including whole virus, components, viral‐like particles. article describes...
Despite the availability of seasonal vaccines and antiviral medications, influenza virus continues to be a major health concern pandemic threat due continually changing antigenic regions surface glycoprotein, hemagglutinin (HA). One emerging strategy for development more efficacious universal is structure-guided design nanoparticles that display conserved HA, such as stem. Using H1 HA subtype establish proof concept, we found tandem copies an alpha-helical fragment from stem region (helix-A)...
Multiple administrations of nanoparticle-based formulations are often a clinical requirement for drug delivery and diagnostic imaging applications. Steady pharmacokinetics nanoparticles is desirable to achieve efficient therapeutic or outcomes over such repeat administrations. While clearance through mononuclear phagocytic system key determinant nanoparticle persistence in vivo, multiple could potentially result altered by evoking innate adaptive immune responses. Plant viral (VNPs)...
Human papillomavirus (HPV) is linked to nearly all cases of cervical cancer. Despite available vaccines, a deeper understanding the immune response HPV needed. α-defensin 5 (HD5), an innate effector peptide, blocks infection multiple sero-types HPV, including high-risk HPV16. While common mechanism anti-viral activity against nonenveloped viruses such as has emerged, there limited how α-defensins bind viral capsids block infection.We have used cryo-electron microscopy (cryoEM), mass...
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Abstract Despite the availability of seasonal vaccines and antiviral medications, influenza virus continues to be a major health concern pandemic threat due continually changing antigenic regions surface glycoprotein, hemagglutinin (HA). One emerging strategy for development more efficacious universal is structure-guided design nanoparticles that display conserved HA, such as stem. Using H1 HA subtype establish proof concept, we found an alpha-helical fragment (helix-A) from stem region can...
Defensins are peptides of the innate immune system with potent antimicrobial activity.Despite strong interest in defensins as potential pharmaceutical compounds, commercial development these has been challenging.New generations modified being pursued to improve their pharmaceuticals.Strategies include peptide mimetics, hybrid peptides, congeners, stabilized conjugates and immobilized [1].Our laboratories have working on understanding molecular mechanisms against adenovirus characterize key...
Pharmacokinetic studies of adenovirus (Ad) vectors after intravascular delivery demonstrate that the majority an administered virus dose is rapidly sequestered from circulation by liver. The molecular determinants target Ad to liver have been found on each capsid proteins, including hexon, penton, and fiber. penton protein in serotypes comprises a hypervariable loop containing RGD motif has shown interact with number cellular integrins upon entry into cell. binding triggers internalization...
Influenza viruses cause millions of infections each year.Unlike influenza A viruses, B infection appears restricted to humans and no zoonotic reservoirs have been identified [1].Although numerous structural studies reported [2-4], less is known about the organization B. Additionally, organizations packaged unpackaged segmented genomic ribonucleoprotein complexes (RNPs) not studied in detail [5].The lack such information hinders on how adaption different culture systems could affect...