A5080131308- Cellular transport and secretion
- Monoclonal and Polyclonal Antibodies Research
- Glycosylation and Glycoproteins Research
- Erythrocyte Function and Pathophysiology
- Heme Oxygenase-1 and Carbon Monoxide
- Microtubule and mitosis dynamics
- Neonatal Health and Biochemistry
- Retinal Development and Disorders
- Toxin Mechanisms and Immunotoxins
- Immunodeficiency and Autoimmune Disorders
- Aldose Reductase and Taurine
- Herpesvirus Infections and Treatments
- Protein purification and stability
- interferon and immune responses
- Biochemical and Molecular Research
- Poxvirus research and outbreaks
- Metal complexes synthesis and properties
- Blood groups and transfusion
- Arsenic contamination and mitigation
- Glutathione Transferases and Polymorphisms
- Plant Reproductive Biology
- Facial Rejuvenation and Surgery Techniques
- Porphyrin Metabolism and Disorders
- Trypanosoma species research and implications
- Cell death mechanisms and regulation
Washington University in St. Louis
2024
Hospital for Sick Children
2024
California University of Pennsylvania
2024
Rush University Medical Center
2024
Johns Hopkins University
2024
Cleveland Clinic
2024
Brigham and Women's Hospital
2024
University of Bristol
2023
Pfizer (Ireland)
2015-2018
Trinity College Dublin
1997-2016
Background: Clinical trials of anti-Aβ monoclonal antibodies in Alzheimer disease (AD) infer target engagement from Aβ positron emission tomography (PET) and/or fluid biomarkers such as cerebrospinal (CSF) Aβ42/40.However, these measure deposits indirectly incompletely.In contrast, postmortem neuropathologic assessments allow direct investigation treatment effects on brain and many other pathologic features.Methods: From a clinical trial dominantly inherited AD, we measured...
The parasite Trypanasoma brucei causes African trypanosomiasis, known as sleeping sickness in humans and nagana domestic animals. These diseases are a major burden the 36 sub-Saharan countries where tsetse fly vector is endemic. Untreated trypanosomiasis fatal current treatments stage-dependent can be problematic during meningoencephalitic stage, no new therapies have been developed recent years drugs low therapeutic index. There need for more effective better understanding of how these...
The partial amino acid sequence of the Fc region an unusual monoclonal immunoglobulin molecule (Goe), which had allotypic markers Gm (b0, b3, b5, s, t, v), rarely encountered in Caucasians, was determined. Protein Goe previously shown to belong gamma 3 subclass by antigenic typing, possess a 3-like hinge and 1-like carboxy-terminal octadecapeptide, bind staphylococcal protein A. resembled that molecules except for presence tyrosine at position 296, alanine 339, histidine positions 435 436....
Dissimilatory sulfite reductases (dSiRs) are crucial enzymes in bacterial sulfur-based energy metabolism, which is likely to have been present some of the earliest life forms on Earth. Several classes dSiRs proposed basis different biochemical and spectroscopic properties. Here, we describe first structure a dSiR from desulforubidin (Drub) class isolated Desulfomicrobium (Dm.) norvegicum. The assembled as a2b2c2, two DsrC proteins bound core [DsrA]2[DsrB]2 unit, reported for desulfoviridin...
Carbon nanotubes (CNTs) did not exhibit strong interactions with Biliverdin IX beta reductase enzyme (BVRB) in water. With the use of noncovalent functionalization by surfactant Triton X-100, surfaces CNTs were changed from hydrophobic to hydrophilic. The hydrophilic surface CNT-Triton conjugate interacts BVRB, thus creating a water-soluble complex. Results ultracentrifugation through sucrose gradient and gel electrophoresis show presence enzyme. Raman spectroscopy confirmed that indeed conjugates.
Significance Immunized animals are a key source of monoclonal antibodies used to treat human diseases. Before clinical use, animal typically “humanized” by laborious and suboptimal methods that transfer their full target binding loops (a.k.a. CDRs) into frameworks. We report an optimal method, where the CDRs from species such as rodents chickens can be adapted fit frameworks in which we have manufacturing confidence. The Augmented Binary Substitution (ABS) process exploits fundamental...
Many vertebrate species express two enzymes that are capable of catalysing the reduction various isomers biliverdin. Biliverdin-IXalpha reductase (BVR-A) is most active with its physiological substrate biliverdin-IXalpha, but can also reduce three other biliverdin IXbeta, IXdelta and IXgamma. Biliverdin-IXbeta (BVR-B) catalyses only IXgamma Therefore, activity BVR-A be measured using biliverdin-IXalpha as a specific substrate. We now show dimethyl esters biliverdin-IXbeta biliverdin-IXdelta...
Eukaryotic cells have developed a diverse repertoire of Rab GTPases to regulate vesicle trafficking pathways. Together with their effector proteins, Rabs mediate various aspects formation, tethering, docking and fusion, but details the biological roles elicited by effectors are largely unknown. Human Rab6 is involved in vesicles at level Golgi via interactions numerous proteins. We previously determined crystal structure complex DENND5, alternatively called Rab6IP1, which comprises two RUN...
Rab GTPases localize to distinct sub-cellular compartments and regulate vesicle trafficking in eukaryotic cells. Yeast Rabs Ypt31/32 Sec4 have 68% homology bind common interactors, yet play roles the transport of exocytic vesicles. The structures not previously been reported uncomplexed state. We describe crystal GTP GDP forms Ypt32 understand molecular basis for function. structure Ypt32(GTP) reveals that switch II conformation is from Sec4(GTP) spite a highly conserved amino acid sequence....
The effect of pH on the initial-rate kinetic behaviour BVR-A (biliverdin-IXα reductase) exhibits an alkaline optimum with NADPH as cofactor, but a neutral NADH cofactor. This has been described dual cofactor and dependent behaviour; however, no mechanism to explain this phenomenon. We present evidence that apparent peak activity observed at phosphate buffer is anion-dependent activation, where inorganic apparently mimics role played by 2′-phosphate in stabilizing interaction between enzyme....
Effectors of the Rab small GTPases are large multi-domain proteins which have proved difficult to express in soluble form Escherichia coli. Generally, effectors recruited a distinct subcellular compartment by active (GTP-bound) Rabs, linked membranes one or two prenylated Cys residues at their C-termini. Following recruitment via Rab-binding domain (RBD), carry out various aspects vesicle formation, transport, tethering and fusion through other domains. Previously, successful purification...
This study has employed mammalian transient expression systems to generate afucosylated antibodies and antibody Fc mutants for rapid candidate screening in discovery early development. While chemical treatment with the fucose analogue 2-fluoro-peracetyl-fucose during only partially produced N-glycans, genetic inactivation of FUT8 gene ExpiCHO-S™ by CRISPR/Cas9 enabled production fully antibodies. Human IgG1 murine IgG2a generated ExpiCHOfut8KO cell line possessed a 8-to-11-fold enhanced...