A5054710722- Monoclonal and Polyclonal Antibodies Research
- Microtubule and mitosis dynamics
- Cancer, Hypoxia, and Metabolism
- Glycosylation and Glycoproteins Research
- Radiopharmaceutical Chemistry and Applications
- Photoreceptor and optogenetics research
- Micro and Nano Robotics
- Cellular Mechanics and Interactions
- Photochromic and Fluorescence Chemistry
- Lung Cancer Research Studies
- Microfluidic and Capillary Electrophoresis Applications
- CRISPR and Genetic Engineering
- RNA and protein synthesis mechanisms
- Photosynthetic Processes and Mechanisms
- Advanced biosensing and bioanalysis techniques
- Protease and Inhibitor Mechanisms
- Light effects on plants
- Protist diversity and phylogeny
- Neuroblastoma Research and Treatments
- Hippo pathway signaling and YAP/TAZ
- Cancer Research and Treatments
- Neuroendocrine Tumor Research Advances
- Microfluidic and Bio-sensing Technologies
- Powder Metallurgy Techniques and Materials
- Advanced Materials and Mechanics
University of Saskatchewan
2016-2025
University of Toronto
2012-2025
Rutgers, The State University of New Jersey
2019
3M (United States)
2012
Cellular Research (United States)
2012
Pennsylvania State University
2004-2010
In-Q-Tel
2010
Total chemical synthesis was used to prepare the mirror image ( D -protein) form of angiogenic protein vascular endothelial growth factor (VEGF-A). Phage display against -VEGF-A screen designed libraries based on a unique small scaffold in order identify high affinity ligand. Chemically synthesized - and L forms ligand showed reciprocal chiral specificity surface plasmon resonance binding experiments: The -protein bound only -VEGF-A, whereas -VEGF-A. ligand, but not inhibited natural VEGF...
Polypeptides composed entirely of d-amino acids and the achiral amino acid glycine (d-proteins) inherently have in vivo properties that are proposed to be near-optimal for a large molecule therapeutic agent. Specifically, d-proteins resistant degradation by proteases anticipated nonimmunogenic. Furthermore, manufactured chemically can engineered other desirable properties, such as improved stability, affinity, pharmacokinetics. Thus, well-designed d-protein would likely significant...
Microtubules (MTs) have been proposed to act mechanically as compressive struts that resist both actomyosin contractile forces and their own polymerization stabilize cell shape. To identify the origin of MT bending, we directly observed bending F-actin transport dynamics in periphery LLC-PK1 epithelial cells. We found is nearly stationary these cells even MTs are deformed, demonstrating not driven by contractility. Furthermore, inhibition myosin II activity through use blebbistatin results...
The small GTPase Rap1 regulates inside-out integrin activation and thereby influences cell adhesion, migration, polarity. Several effectors have been described to mediate the cellular effects of in a context-dependent manner. Radil is emerging as an important Rap effector implicated spreading but molecular mechanisms underlying its functions are unclear. We report here that kinesin KIF14 associates with PDZ domain negatively Rap1-mediated by tethering on microtubules. depletion led increased...
The kinesin-microtubule system plays an important role in intracellular transport and is a model for integrating biomotor-driven into microengineered devices. AC electrokinetics provides novel tool manipulating organizing microtubules solution, enabling new experimental geometries investigating controlling the interactions of microtubule motors vitro. By fabricating microelectrodes on glass substrates generating electric fields across solutions low-ionic-strength buffers, bundles are...
Nectin-4 is an overexpressed biomarker in 60%-70% of triple-negative breast cancer (TNBC) cases and ideal target for radiotherapy PET imaging. In this study, theranostic radioimmunoconjugates were developed using a fully human anti-nectin-4 antibody (N4MU01). The imaging properties therapeutic effectiveness the evaluated TNBC models. Methods: N4MU01 was radiolabeled with 89Zr 225Ac radiotherapy, respectively, xenograft syngeneic Biodistribution [89Zr]Zr-deferoxamine (DFO)-N4MU01...
The binding of photoswitchable molecules to partners forms the basis many naturally occurring light-dependent signaling pathways and various photopharmacological optogenetic tools. A critical parameter affecting function these is thermal half-life light state. Reports in literature indicate that, some cases, a partner can significantly influence half-life, while other cases it has no effect. Here, we present unifying framework for quantitatively analyzing effects on reversion rates. We focus...
Abstract Epidermal growth factor receptor (EGFR) is expressed in approximately 80-85% of colorectal cancer (CRC). While anti-EGFR antibodies benefit some CRC patients, tumors with kirsten rat sarcoma (KRAS) or B-rapidly accelerated fibrosarcoma (BRAF), a proto-oncogene serine/threonine protein kinase mutations are resistant. Here, we developed theranostic approach that uses an antibody-drug conjugate labeled either [225Ac]Ac [89Zr]Zr and evaluated the strategy against KRAS BRAF mutant...
Purpose: Cancer biomarkers like CA125 (MUC-16) are targets for the selective delivery of toxic radiation and/or cytotoxic molecules to tumor loci. MUC-16 is overexpressed in 80% epithelial ovarian cancer (EOC) and 65% pancreatic ductal adenocarcinomas (PDAC). Prognosis EOC PDAC has remained poor with 5-year survival rate between 30-50% 15-20% & respectively, hence, need new treatment approaches. Our lab developed a fully human monoclonal antibody (mAb) that binds specifically...
Abstract Purpose: Targeted radioligand therapy (RLT) and radioimmunotherapy (RIT) have emerged as effective safe treatment modalities for metastatic cancers. Nectin-4 is a Ca2+-independent immunoglobulin-like cell adhesion molecule. Aberrant expression of observed in many cancers notably TNBC NSCLC. No RLT/RIT approved/in advanced clinical development against For the first time, we report efficacy safety 161Tb-labeled anti-Nectin-4 antibody ([161Tb]Tb-DOTA-N4MU01) positive NSCLC mouse...
// Chelsea E. Cunningham 1, * , Shuangshuang Li Frederick S. Vizeacoumar Kalpana Kalyanasundaram Bhanumathy 1 Joo Sang Lee 2 Sreejit Parameswaran Levi Furber Omar Abuhussein 3 James M. Paul Megan McDonald Shaina D. Templeton Hersh Shukla Amr El Zawily Boyd Nezeka Alli Darrell Mousseau 4 Ron Geyer Keith Bonham 5 Deborah H. Anderson Jiong Yan Li-Yuan Yu-Lee 6 Beth A. Weaver 7 Maruti Uppalapati Eytan Ruppin Anna Sablina 8 Andrew Freywald Franco J. 3, Department of Pathology, Cancer Cluster,...
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Kinesins are molecular motors that transport intracellular cargo along microtubules and provide a model system for force generation can be exploited biomotor powered nano- micro-machines. To use this biological microscale transport, the most common approach is to reverse geometry move surfaces functionalized with kinesin motors. The then become potential vehicles sensors lab-on-a-chip applications. A key requirement extracting useful work from confinement control of microtubule movements...
Nature provides an array of proteins that change conformation in response to light. The discovery a complementary bind only the light-state or dark-state their photoactive partner would allow each light-switchable protein be used as optogenetic tool control protein-protein interactions. However, many have no known binding partner, advantages control-precise spatial and temporal resolution-are currently restricted few well-defined natural systems. In addition, affinities kinetics native...
We report a general approach to engineering multivalent d-proteins with antibody-like activities in vivo. Mirror-image phage display and structure-guided design were utilized create d-protein that uses receptor mimicry antagonize vascular endothelial growth factor A (VEGF-A). Selections against the form of VEGF-A using phage-displayed libraries two different domain scaffolds yielded proteins bound distinct interaction sites on VEGF-A. X-ray crystal structures d-protein/VEGF-A complexes used...
Osteosarcoma (OS) is a prevalent primary bone cancer affecting both humans and canines. This study describes initial insights into the interaction of human monoclonal antibody IF3 to an insulin-like growth factor 2 receptor (IGF2R) radiolabeled with either alpha-emitting Actinium-225 (
Abstract Photo‐controlled affinity reagents seek to provide modular spatiotemporal control of bioactivity by conferring photo‐switchability function on an reagent scaffold. Herein we used Rosetta‐based computational methods screen for sites the Fynomer structure attachment photoswitchable cross‐linkers. Both established UV‐based cross‐linkers (azobenzene‐iodoacetamide (IAC)) and azonium‐based efficient red‐light‐switchable cross‐linker, piperazino‐tetra‐ ortho ‐methoxy azobenzene (PIP), were...
Etiological and genetic drivers of osteosarcoma (OS) are not well studied vary from one tumor to another; making it challenging pursue conventional targeted therapy. Recent studies have shown that cation independent mannose-6-phosphate/insulin-like growth factor-2 receptor (IGF2R) is consistently overexpressed in almost all standard patient-derived OS cell lines, an ideal therapeutic target for development antibody-based drugs. Monoclonal antibodies, targeting IGF2R, can be conjugated with...
Photo-control of affinity reagents offers a general approach for high-resolution spatiotemporal control diverse molecular processes. In an effort to develop design principles photo-controlled reagent, we took structure-based the photoswitchable Z-domain, among simplest reagent scaffolds. A chimera, designated Z-PYP, photoactive yellow protein (PYP) and was designed based on concept mutually exclusive folding. NMR analysis indicated that, in dark, PYP domain chimera folded, Z-domain unfolded....