A5077226777- Monoclonal and Polyclonal Antibodies Research
- Glycosylation and Glycoproteins Research
- Radiopharmaceutical Chemistry and Applications
- CAR-T cell therapy research
- Protein purification and stability
- Bacteriophages and microbial interactions
- T-cell and B-cell Immunology
- Global Cancer Incidence and Screening
- Glioma Diagnosis and Treatment
- Galectins and Cancer Biology
- Cell Image Analysis Techniques
- Transgenic Plants and Applications
- Toxin Mechanisms and Immunotoxins
- ATP Synthase and ATPases Research
- Pediatric health and respiratory diseases
- Viral gastroenteritis research and epidemiology
- 14-3-3 protein interactions
- Autoimmune Bullous Skin Diseases
- Ubiquitin and proteasome pathways
- Axon Guidance and Neuronal Signaling
- Phagocytosis and Immune Regulation
- Cancer Research and Treatments
- Colorectal Cancer Screening and Detection
- Bacterial Infections and Vaccines
- Antibiotic Resistance in Bacteria
University of Ottawa
2019-2025
National Research Council Canada
2015-2024
National Academies of Sciences, Engineering, and Medicine
2024
McMaster University
2023
Juravinski Hospital
2022
Philadelphia University
2020
Temple University
2020
Rutgers, The State University of New Jersey
2014
University of Utah
2012-2013
Huntsman Cancer Institute
2013
Previous studies found that uninsured and Medicaid insured cancer patients have poorer outcomes than with private insurance. We examined the association between health insurance status survival of New Jersey 18-64 diagnosed seven common cancers during 1999-2004. Hazard ratios (HRs) 95% confidence intervals for 5-year cause-specific were calculated from Cox proportional hazards regression models; was primary predictor adjustment other significant factors in univariate chi-square or...
ABSTRACT Siderophores have been identified as virulence factors in the opportunistic fungal pathogen Aspergillus fumigatus . The 14-pass transmembrane protein MirB is postulated to function a siderophore transporter, responsible for uptake of hydroxamate N,N ′, N ″-triacetylfusarinine C (TAFC). Our aim was identify amino acids A. that are crucial TAFC. Site-directed mutagenesis used create mutants. Expression wild-type and mutant proteins Saccharomyces cerevisiae strain PHY14, which lacks...
Northern peatlands are important global C reservoirs, largely because of their slow rates microbial mineralization. Particularly in sites that heavily influenced by anthropogenic disturbances, there is scant information about ecology and whether or not community structure influences greenhouse gas production. This work characterized communities bacteria archaea using terminal restriction fragment length polymorphism sequence analysis 16S rRNA functional genes across eight natural, mined,...
Prolonged serum half-life is required for the efficacy of most protein therapeutics. One strategy extension to exploit long circulating albumin by incorporating a binding moiety that recognizes albumin. Here, we describe camelid single-domain antibodies (VHHs) bind albumins multiple species with moderate high affinity at both neutral and endosomal pH significantly extend half-lives proteins in rats from minutes days. We serendipitously identified an additional VHH (M75) naturally...
Antibodies that cross-react with multiple isoforms or homologue of a given protein are often desirable, especially in therapeutic applications. Here, we report the identification several unique, clonally unrelated, single-domain antibodies (sdAbs) bind to serum albumin orthologues (human, rhesus, rat and mouse) low-to-medium nanomolar affinity from llama immunized only human albumin. Using single-round panning phage-displayed sdAb library against albumins next-generation DNA sequencing, were...
Epidermal growth factor family receptor (EGFR) is commonly overexpressed in many solid tumors and an attractive target for chimeric antigen (CAR)-T therapy, but as EGFR also expressed at lower levels healthy tissues a therapeutic strategy must balance antigenic responsiveness against the risk of on-target off-tumor toxicity. Herein, we identify several camelid single-domain antibodies (also known nanobodies) that are effective targeting moieties CARs (EGFR-sdCARs) with very strong reactivity...
Abstract Resistance to genotoxic therapies and tumor recurrence are hallmarks of glioblastoma (GBM), an aggressive brain tumor. In this study, we investigated functional drivers post-treatment recurrent GBM through integrative genomic analyses, genome-wide genetic perturbation screens in patient-derived models independent lines validation. Specific dependencies were found consistent across models, accompanied by increased mutational burden differential transcript protein expression compared...
The study's purpose was to investigate thyroid cancer incidence time trends, birth cohort effects, and association with socioeconomic status (SES) in New Jersey (NJ), a high state, using NJ State Cancer Registry data. Thyroid rates each sex, nearly all age groups, two major histologies stages significantly increased between 1979 2006. For age-specific began greatly increasing the 1924 and, generally, highest rate for five-year group occurred latest diagnosis period. were higher Census tracts...
Abstract Up-regulation of epidermal growth factor receptor (EGFR) is a hallmark many solid tumors, and inhibition EGFR signaling by small molecules antibodies has clear clinical benefit. Here, we report the isolation functional characterization novel camelid single-domain (sdAbs or VHHs) directed against human EGFR. The source these VHHs was llama immunized with cDNA encoding ectodomain alone (no protein cell boost), which notable in that genetic immunization large, outbred animals generally...
Staphylococcal protein A (SpA) and streptococcal G (SpG) affinity chromatography are the gold standards for purifying monoclonal antibodies (mAbs) in therapeutic applications. However, camelid VHH single-domain Abs (sdAbs or VHHs) not bound by SpG only sporadically SpA. Currently, VHHs require tag-based purification, which limits their potential adds considerable complexity cost to production. Here we describe a simple rapid mutagenesis-based approach designed confer SpA binding upon priori...
Multispecific antibodies that bridge immune effector and tumor cells have shown promising preclinical clinical efficacies. Here, we isolated characterized novel llama single-domain (sdAbs) against CD16. One sdAb, NRC-sdAb048, bound recombinant human cynomolgus monkey CD16 ectodomains with equivalent affinity (KD: 1 nM) but did not recognize murine Binding was similar for CD16a expressed on NK CD16b (NA2) neutrophils dramatically weaker ∼6 μM) the (NA1) allotype. The sdAb stained primary...
The epitope specificity of therapeutic antibodies is often critical to their efficacy and mode action. Here, we report the isolation single-domain (sdAbs) against a pre-specified TGF-β3: namely, site interaction between cytokine its cell-surface type II receptor. By panning phage-displayed immune llama VhH library TGF-β3 using competitive elution with soluble dimeric receptor ectodomain in tandem next-generation DNA sequencing, identified several sdAbs that competed for binding neutralized...
Enterohemorrhagic Escherichia coli (EHEC) has consistently been one of the foremost foodborne pathogen threats worldwide based on past 30 years surveillance. EHEC primarily colonizes bovine gastrointestinal (GI) tract from which it can be transmitted to nearby farm environments and remain viable for months. There is an urgent need effective easily implemented pre-harvest interventions curtail contamination food water supply. In effort address this problem, we isolated single-domain...
Broadly neutralizing antibodies (bNt Abs) against HIV-1 are rarely produced during natural infection, and efforts to induce such Abs by vaccination have been unsuccessful. Thus, elucidating the nature cellular origins of bNt is a high priority for vaccine research. As monoclonal (MAbs) 2F5, 4E10 2G12 reported bind select autoantigens, we investigated whether these MAbs display broader range autoreactivity how their compares with that pathogenic autoAbs.An autoantigen microarray comprising...
Human autonomous VH/VL single-domain antibodies (sdAbs) are attractive therapeutic molecules, but often suffer from suboptimal stability, solubility and affinity for cognate antigens. Most commonly, human sdAbs have been isolated in vitro display libraries constructed via synthetic randomization of rearranged domains. Here, we describe the design characterization three novel sdAb through a process of: (i) exhaustive biophysical 20 potential library scaffolds, including assessment expression...
Pseudomonas aeruginosa is an opportunistic pathogen that inherently resistant to many antibiotics and represents increasing threat due the emergence of drug-resistant strains. There a pressing need develop innovative antimicrobials against this pathogen. In study, we identified O-specific antigen (OSA) P. serotype O6 as novel target for therapeutic intervention. Binding monoclonal antibodies antigen-binding fragments therefrom OSA leads rapid outer membrane destabilization inhibition cell growth.