A5003313387- Monoclonal and Polyclonal Antibodies Research
- Ultrasound Imaging and Elastography
- Medical Imaging Techniques and Applications
- Protein purification and stability
- Angiogenesis and VEGF in Cancer
- Glycosylation and Glycoproteins Research
- Advanced Radiotherapy Techniques
- Viral Infectious Diseases and Gene Expression in Insects
- Ultrasound and Hyperthermia Applications
- Photoacoustic and Ultrasonic Imaging
- Chronic Lymphocytic Leukemia Research
- Cancer, Hypoxia, and Metabolism
- Protein Kinase Regulation and GTPase Signaling
- Ubiquitin and proteasome pathways
- Fungal and yeast genetics research
- MRI in cancer diagnosis
- Renal and related cancers
- Biotin and Related Studies
- Blood disorders and treatments
- Multiple Myeloma Research and Treatments
- Receptor Mechanisms and Signaling
- Bone Metabolism and Diseases
- Alkaline Phosphatase Research Studies
- Bone health and osteoporosis research
- Cardiac and Coronary Surgery Techniques
Amgen (United States)
2004-2025
Biolog (United States)
2020
Augusta University
2020
Brain Tumour Research
2009
NeuroDevelopment Center
2009
Hospital for Sick Children
2009
SickKids Foundation
2009
Biologie du Développement et Cellules Souches
2009
Western University
2000-2008
London Health Sciences Centre
2008
Abstract The development of bone-rebuilding anabolic agents for treating bone-related conditions has been a long-standing goal. Genetic studies in humans and mice have shown that the secreted protein sclerostin is key negative regulator bone formation. More recently, administration sclerostin-neutralizing monoclonal antibodies rodent pharmacologic inhibition results increased formation, mass, strength. To explore effects primates, we administered humanized antibody (Scl-AbIV) to gonad-intact...
Using the yeast two-hybrid system, we have identified a human ubiquitin-conjugating enzyme (hE2-25K) as protein that interacts with gene product for Huntington disease (HD) (Huntingtin). This has complete amino acid identity bovine E2-25K and striking similarity to UBC-1, −4 −5 enzymes of Saccharomyces cerevisiae. is highly expressed in brain slightly larger recognized by an anti-E2-25K polyclonal antibody selectively regions affected HD. The huntingtin-E2-25K interaction not obviously...
Abstract Subpopulations of tumorigenic cells have been identified in many human tumors, although these may not be very rare some types cancer. Here, we report that medulloblastomas arising from Patched-1–deficient mice contain a subpopulation show neural precursor phenotype, clonogenic and multilineage differentiation capacity, activated Hedgehog signaling, wild-type Patched-1 expression, the ability to initiate tumors following allogeneic orthotopic transplantation. The normal stem cell...
Casein kinase II (CKII) is a protein serine/threonine known to control the activity of variety regulatory nuclear proteins. This enzyme has tetrameric structure composed two catalytic (α and/or α′) subunits and β subunits. We have examined subunit composition complexes purified bovine CKII by immunoprecipitation using α, α′, or subunit-specific antibodies. These experiments indicate that can exist as homotetramers (i.e. α2β2 α2′β2) well heterotetramers αα′β2). To further examine interactions...
Abstract Liver metastasis is a clinically significant contributor to the mortality associated with melanoma, colon, and breast cancer. Preclinical mouse models are essential study of liver metastasis, yet their utility has been limited by inability this dynamic process in noninvasive longitudinal manner. This shows that three-dimensional high-frequency ultrasound can be used noninvasively track growth metastases evaluate potential chemotherapeutics experimental models. produced mesenteric...
Abstract Objective Sclerostin plays a major role in regulating skeletal bone mass, but its effects articular cartilage are not known. The purpose of this study was to determine whether genetic loss or pharmacologic inhibition sclerostin has an impact on knee joint cartilage. Methods Expression determined and tissue obtained from mice, rats, human subjects, including patients with osteoarthritis (OA). Mice knockout (KO) sclerostin‐neutralizing monoclonal antibody (Scl‐Ab) aged male rats...
The catalytic subunits of protein kinase CK2, CK2α and CK2α′, are closely related to each other but exhibit functional specialization. To test the hypothesis that specific functions CK2α′ mediated by interaction partners, we used yeast two-hybrid system identify CK2α- or CK2α′-binding proteins. We report identification characterization a novel CK2-interacting protein, designated CKIP-1, interacts with CK2α, not in system. CKIP-1 also <i>in vitro</i> is co-immunoprecipitated from cell...
Myxoma virus (MV) is a rabbit-specific poxvirus, whose unexpected tropism to human cancer cells has led studies exploring its potential use in oncolytic therapy. MV infects wide range of vitro, manner intricately linked the cellular activation Akt kinase. also been successfully used for treating glioma xenografts immunodeficient mice. This study examines effectiveness primary and metastatic mouse tumors immunocompetent C57BL6 We have found that several tumor cell lines, including B16...
Biologic drug discovery pipelines are designed to deliver protein therapeutics that have exquisite functional potency and selectivity while also manifesting biophysical characteristics suitable for manufacturing, storage, convenient administration patients. The ability use computational methods predict properties from sequence, potentially in combination with high throughput assays, could decrease timelines increase the success rates therapeutic developability engineering by eliminating...
Protein kinase CK2 is a tetrameric enzyme composed of two catalytic (α and/or α′) subunits and regulatory (β) subunits. Because CK2β synthesized in excess CK2α, we hypothesized that formation homodimers precedes the incorporation into complexes. To test this hypothesis, cotransfected cells with epitope-tagged variants CK2β. The results these cotransfection studies demonstrate interactions between take place absence CK2α. Together from previous biosynthetic labeling studies, suggest occurs...
The objective of this study was to determine the time-course computed tomography (CT) contrast enhancement an iodinated blood-pool agent.Five C57BL/6 mice were anesthetized, imaged at baseline, and given agent. Micro-CT scans acquired 0, 0.25, 0.5, 1, 2, 4, 8, 24 hours after injection. mean CT number determined in a region interest 7 organs.The plotted as function time for each organ. We identified imaging window immediately injection suitable visualizing vascular system second liver...
Objectives: To determine a timepoint after contrast injection that yields equal liver parenchymal and vascular enhancement in micro-computed tomography images. evaluate the utility of images acquired during this time period for noninvasive measurement liver-tumor volume. Materials Methods: The imaging was determined by quantifying kinetics Fenestra VC (0.015 mL/g) NIH III mice. In respiratory-gated tumor bearing mice, ability to measure volume evaluated with variability study, comparing vivo...
Abstract T cell engaging bispecific antibody constructs (BiTE®), such as blinatumomab which targets CD19-positive cells, have shown great promise for treating certain hematological malignancies. Blinatumomab comprises a single chain Fv (scFv) that binds CD19 and scFv the CD3 protein. The molecular weight of this “canonical” BiTE® is ~ 55 kDa, making it susceptible to kidney-mediated clearance resulting in short serum half-life (~ 4 hours). To maintain effective concentrations, canonical must...
The identification and quantification of tumour volume measurement variability is imperative for proper study design longitudinal non-invasive imaging pre-clinical mouse models cancer. Measurement will dictate the minimum detectable change, which in turn influences scheduling sessions interpretation observed changes volume. In this paper, quantified measurements from 3D high-frequency ultrasound images murine liver metastases. Experimental B16F1 metastases were analysed different size ranges...
Objectives: To determine if intraperitoneally (IP) administered contrast (iohexol), used in conjunction with a liver-specific agent (Fenestra), can improve measurement precision and accuracy when quantifying tumor volume from micro-CT images of liver metastasis model. Materials Methods: We compared acquired Fenestra alone to the combination IP iohexol. The variability tumor-burden was evaluated for both techniques. vivo techniques determined by comparison quantified ex images. Results:...
Protein-based biotherapeutics are produced in engineered cells through complex processes and may contain a wide variety of variants post-translational modifications that must be monitored or controlled to ensure product quality. Recently, low level (~1-5%) impurity was observed number proteins derived from stably transfected Chinese hamster ovary (CHO) using mass spectrometry. These molecules include antibodies Fc fusion where is on the C-terminus construct. By liquid chromatography-mass...
Wnt-modulator in surface ectoderm (WISE) is a secreted modulator of Wnt signaling expressed the adult kidney. Activation has been observed renal transplants developing interstitial fibrosis and tubular atrophy; however, whether WISE contributes to chronic changes not well understood. Here, we found moderate high expression mRNA rat model transplantation kidneys from normal rats. Treatment with neutralizing antibody against improved proteinuria graft function, which correlated higher levels...
We are entering an era in which therapeutic proteins assembled using building block-like strategies, with no standardized schema to discuss these formats. Existing nomenclatures, like AbML, sacrifice human readability for precision. Therefore, considering even a dozen such formats, combination hundreds of possible targets, can create confusion and increase the complexity drug discovery. To address this challenge, we introduce Verified Taxonomy Antibodies (VERITAS). This classification...
Full-length immunoglobulins (Igs) are widely considered difficult to crystallize because of their large size, N-linked glycosylation, and flexible hinge region. However, numerous cases intracellular Ig crystallization reported in plasma cell dyscrasias. What makes some clones more prone during biosynthesis as well the biochemical biological requirements for this cryptic event poorly understood. To investigate underlying process we searched model IgGs that can induce crystalline inclusions...