- Nanoplatforms for cancer theranostics
- Monoclonal and Polyclonal Antibodies Research
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Photodynamic Therapy Research Studies
- HIV Research and Treatment
- Immune cells in cancer
- SARS-CoV-2 and COVID-19 Research
- Meta-analysis and systematic reviews
- Clinical practice guidelines implementation
- CAR-T cell therapy research
- Cancer Immunotherapy and Biomarkers
- Click Chemistry and Applications
- Experimental Behavioral Economics Studies
- Advanced Cellulose Research Studies
- RNA Interference and Gene Delivery
- vaccines and immunoinformatics approaches
- Bacteriophages and microbial interactions
- Porphyrin and Phthalocyanine Chemistry
- Nanocomposite Films for Food Packaging
- Immunotherapy and Immune Responses
- Glycosylation and Glycoproteins Research
- Online Learning and Analytics
- Nanoparticle-Based Drug Delivery
- Hydrogels: synthesis, properties, applications
- Advanced Drug Delivery Systems
West Virginia University
2023-2025
Footscray Hospital
2025
Western Health
2025
West Virginia University Hospitals
2025
National Institute of Allergy and Infectious Diseases
2021-2024
National Institutes of Health
2021-2024
Centre in Green Chemistry and Catalysis
2021-2024
McGill University
2021-2024
Cullinan Oncology (United States)
2023-2024
University of British Columbia
2018-2023
Defenses against SARS-CoV-2 variants Our key defense the COVID-19 pandemic is neutralizing antibodies virus elicited by natural infection or vaccination. Recent emerging viral have raised concern because of their potential to escape antibody neutralization. Wang et al . identified four from early-outbreak convalescent donors that are potent 23 variants, including concern, and characterized binding spike protein severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Yuan examined...
The rapid spread of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) B.1.1.529 (Omicron) variant and its resistance to neutralization by vaccinee convalescent sera are driving a search for monoclonal antibodies with potent neutralization. To provide insight into effective neutralization, we determined cryo-electron microscopy structures evaluated receptor binding domain (RBD) their ability bind neutralize B.1.1.529. Mutations altered 16% RBD surface, clustered on an ridge...
Photothermal therapy makes use of photothermal sensitizers and laser light to thermally ablate diseased tissues. Porphysome nanoparticles offer a nontoxic alternative inorganic nanocrystals for the efficient conversion into heat. Mn(3+) ions were incorporated directly building blocks our porphysome nanoparticles, thus imparting MRI sensitivity while simultaneously improving photostability maintaining high efficiency. Mn porphysomes are as photothermally effective free-base can rival...
PET friendly: Labels for imaging are incorporated into completely organic porphysomes by using a fast (30 min), one-pot, high-yielding (>95 %) procedure to produce highly stable (>48 h) radiolabeled nanoparticles that show the highest specific activity ever reported 64Cu-labeled nanoparticle. These 64Cu-porphysomes can be accurately and noninvasively tracked in vivo. Detailed facts of importance specialist readers published as "Supporting Information". Such documents peer-reviewed, but not...
Porphyrin based photosensitizers are useful agents for photodynamic therapy (PDT) and fluorescence imaging of cancer. Porphyrins also excellent metal chelators forming highly stable metallo-complexes making them efficient delivery vehicles radioisotopes. Here we investigated the possibility incorporating (64)Cu into a porphyrin-peptide-folate (PPF) probe developed previously as folate receptor (FR) targeted fluorescent/PDT agent, evaluated potential turning resulting (64)Cu-PPF positron...
Prostate cancer is the most common among men and second cause of male cancer-related deaths. There are currently three critical needs in prostate imaging to personalize treatment: (1) accurate intraprostatic for multiple foci extra-capsular extent; (2) monitoring local systemic treatment response predicting recurrence; (3) more sensitive occult bone metastases. Recently, our lab developed porphysomes, inherently multimodal, all-organic nanoparticles with flexible robust radiochemistry....
Assessing the process used to synthesize evidence in clinical practice guidelines enables users determine trustworthiness of recommendations. Clinicians are increasingly dependent on keep up with vast quantities medical literature, and followed avoid malpractice suits. We aimed assess whether systematic methods were when synthesizing for guidelines; type review cited support
Abstract Lassa virus (LASV) infection is expanding outside its traditionally endemic areas in West Africa, posing a pandemic biothreat. LASV-neutralizing antibodies, moreover, have proven difficult to elicit. To gain insight into LASV neutralization, here we develop prefusion-stabilized glycoprotein trimer (GPC), pan it against phage libraries comprising single-domain antibodies (nanobodies) from shark and camel, identify one, D5, which neutralizes LASV. Cryo-EM analyses reveal D5 recognize...
Significance Hyperpolarized [1- 13 C]pyruvate magnetic resonance spectroscopic imaging (MRSI), which measures C]pyruvate-to-[1- C]lactate conversion, has been widely explored as a metabolic-imaging modality interpreted to reflect LDHA activity and glycolytic flux. However, we show definitively that hyperpolarized conversion rates are primarily functional readout of transmembrane influx mediated by MCT1, providing mechanistic reinterpretation redirection clinical translation.
Background The presence of a highly immunosuppressive tumor microenvironment has limited the success immune checkpoint therapy (ICT). Immune suppressing myeloid cells with increased production reactive oxygen species are critical drivers this microenvironment. Strategies to limit these needed enhance response ICT. Methods To evaluate contribution myeloperoxidase (MPO), lineage-restricted enzyme and major source species, mediating ICT response, we compared treatment outcome composition in...
A solid-phase method favors the formation of Shiff-bases from chitosan and aldehydes subsequent reduction. This provides access to alkylated chitosans with high degrees functionalization low process mass intensity.
The COVID-19 pandemic highlights an urgent need for vaccines that confer protection from SARS-CoV-2 infection. One approach to effective vaccine may be through the display of spikes on surface virus-like particles, in a manner structurally mimicking native virus. Here we report development Newcastle disease particles (NDVLPs) displaying prefusion-stabilized spike ectodomain (S2P). Immunoassays with SARS-CoV-2-neutralizing antibodies revealed antigenicity S2P-NDVLP generally similar soluble...
Since the outbreak of COVID-19 pandemic, widespread infections have allowed SARS-CoV-2 to evolve in human, leading emergence multiple circulating variants. Some these variants show increased resistance vaccine-elicited immunity, convalescent plasma, or monoclonal antibodies. In particular, mutations spike drawn attention. To facilitate isolation neutralizing antibodies and monitoring vaccine effectiveness against variants, we designed produced biotin-labeled molecular probes variant spikes...
Abstract Cholangiocyte organoids can be used to model liver biliary disease; however, both a defined matrix emulate cholangiocyte self‐assembly and the mechano‐transduction pathways involved therein remain elusive. A series of viscoelastic hyaluronan hydrogels culture primary cholangiocytes are designed it is found that by mimicking stress relaxation rate tissue, organoid growth induced expression Yes‐associated protein (YAP) target genes could significantly increased. Strikingly, inhibition...
We report the development and characterization of an organic, photonic nanoparticle, Mn-porphysome. Capable photothermal therapy, photoacoustic tomography, magnetic resonance imaging, exhibiting exception photostability, Mn-porphysomes show great promise.
Repeat antigens, such as the Plasmodium falciparum circumsporozoite protein (PfCSP), use both sequence degeneracy and structural diversity to evade immune response. A few PfCSP-directed antibodies have been identified that are effective at preventing malaria infection, including CIS43, but how these repeat-targeting might be improved has unclear. Here, we engineered a humanized mouse model in which B cells expressed inferred human germline CIS43 (iGL-CIS43) cell receptors used vaccination...
The emergence of highly transmissible SARS-CoV-2 variants concern (VOC) that are resistant to therapeutic antibodies highlights the need for continuing discovery broadly reactive antibodies. We identify four receptor-binding domain targeting from three early-outbreak convalescent donors with potent neutralizing activity against 12 including B.1.1.7 and B.1.351 VOCs. Two them ultrapotent, sub-nanomolar neutralization titers (IC50 <0.0006 0.0102 μ g/mL; IC80 < 0.0006 0.0251 g/mL). define...
Elicitation of antibodies that neutralize the tier-2 neutralization-resistant isolates typify HIV-1 transmission has been a long-sought goal. Success with prefusion-stabilized envelope trimers eliciting autologous neutralizing reported in multiple vaccine-test species, though not humans. To investigate elicitation humans, here, we analyze B cells from phase I clinical trial "DS-SOSIP"-stabilized trimer strain BG505, identifying two antibodies, N751-2C06.01 and N751-2C09.01 (named for...
Immunotherapies are effective for cancer treatment but limited in 'cold' tumor microenvironments due to a lack of infiltrating CD8+ T cells, key players the anti-cancer immune response. The onset COVID-19 pandemic sparked widespread use mRNA-formulated vaccines and is well documented that vaccination induces Th1-skewed Here, we evaluated effects an intratumoral injection mRNA vaccine subcutaneous melanoma mouse models. Tumor growth survival studies following single showed significant...
ABSTRACT Introduction There are numerous guidelines offering varying advice on the management of adrenal incidentalomas. The American College Radiology (ACR) white paper recommends no follow‐up for lesions with benign appearances. Our aim was to audit indications CT in context ACR recommendations and assess long‐term outcome these incidental lesions. Methods A retrospective cohort study performed identifying patients who had undergone from 1 January 2016 31 December 2018. Patients symptoms...
Abstract Pancreatic ductal adenocarcinoma (PDAC) is a deadly disease with survival rate under 13%. Treatments like immunotherapy and chemotherapy are ineffective in PDAC due to the immunosuppressive tumor microenvironment, which tumor-associated neutrophils (TANs) major component. The function of TANs has been shown depend upon increased production reactive oxygen species, myeloperoxidase being source it. We investigated contribution mediating immunosuppression using orthotopic models...