A5001385114- Monoclonal and Polyclonal Antibodies Research
- Chronic Lymphocytic Leukemia Research
- Bacterial Genetics and Biotechnology
- Asthma and respiratory diseases
- Mast cells and histamine
- Chronic Myeloid Leukemia Treatments
- Escherichia coli research studies
- Epigenetics and DNA Methylation
- RNA and protein synthesis mechanisms
- Liver physiology and pathology
- Immunotherapy and Immune Responses
- MicroRNA in disease regulation
- HER2/EGFR in Cancer Research
- Acute Lymphoblastic Leukemia research
- Cancer Cells and Metastasis
- Cancer therapeutics and mechanisms
- Advanced Breast Cancer Therapies
- Lymphoma Diagnosis and Treatment
- Antibiotic Resistance in Bacteria
- Polyamine Metabolism and Applications
- Protease and Inhibitor Mechanisms
- Acute Myeloid Leukemia Research
- Virus-based gene therapy research
- Ubiquitin and proteasome pathways
- RNA Interference and Gene Delivery
Dallas Nephrology Associates
2020
Genentech
2011-2014
Kaiser Permanente South San Francisco Medical Center
2013
Significance The outer membrane of Gram-negative bacteria presents a formidable barrier to the discovery new antibiotics needed combat infections by multidrug-resistant bacteria. Targeting essential proteins or processes directly exposed environment could bypass this obstacle. Here, we describe monoclonal antibody that selectively and potently antagonizes BamA, which folds inserts integral β-barrel proteins, binding surface-exposed BamA epitope and, as result, inhibits bacterial cell growth....
Cancer stem cells (CSCs) are hypothesized to actively maintain tumors similarly how their normal counterparts replenish differentiated cell types within tissues, making them an attractive therapeutic target for the treatment of cancer. Because most CSC markers also label tissue cells, it is unclear selectively without compromising homeostasis. We evaluated a strategy that targets surface leucine-rich repeat-containing G protein-coupled receptor 5 (LGR5), well-characterized and marker, with...
T cell–dependent bispecific antibodies with bivalent low affinity binding to HER2 are more selective for tumor cells that overexpress the target.
Hepsin, a type II transmembrane serine protease, is strongly up-regulated in prostate cancer. Hepsin overexpression mouse cancer model resulted tumor progression and metastasis, associated with basement membrane disorganization. We investigated whether hepsin enzymatic activity was linked to the defects by examining its ability initiate plasminogen/plasmin proteolytic pathway. Because plasminogen not processed hepsin, we upstream activators, urokinase-type activator (uPA) tissue-type...
The treatment of acute myeloid leukemia (AML) has not significantly changed in 40 years. Cytarabine- and anthracycline-based chemotherapy induction regimens (7 + 3) remain the standard care, most patients have poor long-term survival. reapproval Mylotarg, an anti-CD33-calicheamicin antibody-drug conjugate (ADC), demonstrated ADCs as a clinically validated option to enhance effectiveness therapy. We are interested developing next-generation ADC for AML improve upon initial success...
Hepatocellular carcinomas (HCCs) constitute one of the few cancer indications for which mortality rates continue to rise. While Notch signaling dictates a key progenitor lineage choice during development, its role in HCC has remained controversial. Using therapeutic antibodies targeting ligands and receptors screen over 40 patient-derived xenograft models, we here identify progenitor-like HCCs that crucially depend on tumor-intrinsic JAG1-NOTCH2 signal. Inhibiting this signal induces tumor...
Hepatocellular carcinomas (HCCs) constitute one of the few cancer indications for which mortality rates continue to rise. While Notch signaling dictates a key progenitor lineage choice during development, its role in HCC has remained controversial. Using therapeutic antibodies targeting ligands and receptors screen over 40 patient-derived xenograft models, we here identify progenitor-like HCCs that crucially depend on tumor-intrinsic JAG1-NOTCH2 signal. Inhibiting this signal induces tumor...
Human cytomegalovirus (HCMV) is the most common cause of congenital virus infection. Congenital HCMV infection occurs in 0.2–1% all births, and causes birth defects developmental abnormalities, including sensorineural hearing loss delay. Several key studies have established guinea pig as a tractable model for study shown that polyclonal antibodies can be protective [1]–[3]. In this study, we demonstrate an anti-guinea CMV (GPCMV) glycoprotein H/glycoprotein L neutralizing monoclonal antibody...
Human β-tryptase, a tetrameric trypsin-like serine protease, is an important mediator of allergic inflammatory responses in asthma. Antibodies generally inhibit proteases by blocking substrate access binding to active sites or exosites allosteric modulation. The bivalency IgG antibodies can increase potency via avidity, but has never been described as essential for activity. Here we report inhibitory anti-tryptase antibody with bivalency-driven mechanism action. Using biochemical and...
Outer membrane proteins (OMPs) in Gram-negative bacteria are essential for a number of cellular functions including nutrient transport and drug efflux. Escherichia coli BamA is an component the OMP β-barrel assembly machinery potential novel antibacterial target that has been proposed to undergo large (~15 Å) conformational changes. Here, we explored methods isolate anti-BamA monoclonal antibodies (mAbs) might alter function this ultimately lead bacterial growth inhibition. We first...
BamA is an essential component of the β-barrel assembly machine (BAM) in outer membranes Gram-negative bacteria. We have used a recently described inhibitory anti-BamA antibody, MAB1, to identify molecular requirements for BAM function. Resistance this antibody can be achieved through changes membrane or by amino acid substitutions that allosterically affect response MAB1. Sensitivity MAB1 perturbing By using activity and functional assays as proxies function, we link fluidity activity,...
Outer membrane proteins (OMPs) in Gram-negative bacteria dictate permeability of metabolites, antibiotics, and toxins. Elucidating the structure-function relationships governing OMPs within native environments remains challenging. We constructed a diverse library >3000 monoclonal antibodies to assess roles extracellular loops (ECLs) LptD, an essential OMP that inserts lipopolysaccharide into outer Escherichia coli. Epitope binning mapping experiments with LptD-loop-deletion mutants...
Multi-transmembrane proteins are especially difficult targets for antibody generation largely due to the challenge of producing a protein that maintains its native conformation in absence stabilizing membrane. Here, we describe an immunization strategy successfully resulted identification monoclonal antibodies bind specifically extracellular epitopes 12 transmembrane protein, multi-drug resistant 4 (MRP4). These were developed following hydrodynamic tail vein with cytomegalovirus (CMV)...
Early success with brentuximab vedotin in treating classical Hodgkin lymphoma spurred an influx of at least 20 monomethyl auristatin E (MMAE) antibody-drug conjugates (ADCs) into clinical trials. While three MMAE-ADCs have been approved, most these are no longer being investigated Some show limited or efficacy tolerated doses, but even for drugs driving initial remissions, tumor regrowth and metastasis often rapidly occur. Here we describe the development second-generation therapeutic ADCs...
Monoclonal antibodies (mAbs) have enabled numerous basic research discoveries and therapeutic approaches for many protein classes. However, there still exist a number of target classes, such as multi-pass membrane proteins, which antibody discovery is difficult, due in part to lack high quality, recombinant protein. Here we describe the impact several parameters on antigen expression development mAbs against human claudin 4 (CLDN4), potential multi-indication cancer target. Using gene...
Abstract Hepatocellular carcinomas (HCCs) constitute one of the few cancer indications for which mortality rates continue to rise. While Notch signaling dictates a key progenitor lineage choice during development, its role in HCC has remained controversial. Using therapeutic antibodies targeting ligands and receptors screen over 40 patient-derived xenograft models, we here identify progenitor-like HCCs that crucially depend on tumor-intrinsic JAG1-NOTCH2 signal. Inhibiting this signal...
Aim: Tryptase is a tetrameric trypsin-like serine protease contained within the secretory granules of mast cells and an important mediator allergic inflammatory responses in respiratory diseases. Detection active tryptase airway may provide information about asthma other Materials & Methods: An activity based probe has been incorported immunoassay to allow for measurement human tissues. Results: A specific Simoa measure nasosorption samples was developed qualified using activity-based label...
Abstract LGR5 (GPR49) is a Wnt pathway downstream target gene. It has already been confirmed that gene up regulated by APC or β-catenin mutation. recently identified as biomarker on the human and murine intestinal colon stem cells. Our expression data shows highly expressed in cancer, with minimal normal tissue. strategy this project to eliminate tumor cells drug conjugated antibody. goal find cell marker develop antibody Here we developed characterized both anti-LGR5 phage monoclonal...
Severe asthma patients with low type 2 inflammation derive less clinical benefit from therapies targeting cytokines and have significant unmet medical needs. We show that mast cell tryptase is elevated in severe patients, correlating greater disease severity, but independent of biomarker status. Active β-tryptase allele count correlates blood levels, carrying more active alleles anti-IgE treatment. generated a noncompetitive inhibitory antibody against human β-tryptase, which dissociates...
<p>S1: Comparison of CLL-1 and CD33 expression level in 70 AML patients. S2: Internalization locolization anti-CLL-1 antibody</p>
<p>hydroxyl radical footprinting of hu6E7.N54A</p>