A5012959704- Cancer, Hypoxia, and Metabolism
- Immune cells in cancer
- Nanoplatforms for cancer theranostics
- Cancer Research and Treatments
- Redox biology and oxidative stress
- Traumatic Brain Injury and Neurovascular Disturbances
- Endoplasmic Reticulum Stress and Disease
- Nerve injury and regeneration
- Hemoglobin structure and function
- Acute Ischemic Stroke Management
- Signaling Pathways in Disease
- Glioma Diagnosis and Treatment
- Adipose Tissue and Metabolism
- Heme Oxygenase-1 and Carbon Monoxide
- Neuroinflammation and Neurodegeneration Mechanisms
- Sulfur Compounds in Biology
- Complement system in diseases
- Virus-based gene therapy research
- Anesthesia and Neurotoxicity Research
- Sirtuins and Resveratrol in Medicine
- Liver physiology and pathology
- Blood groups and transfusion
- Metal-Catalyzed Oxygenation Mechanisms
- Cerebrovascular and Carotid Artery Diseases
- Glutathione Transferases and Polymorphisms
Catalyst Biosciences (United States)
2020-2024
Omniox (United States)
2014-2022
Community Catalyst
2022
Gladstone Institutes
2009-2021
University of California, San Francisco
2009-2015
La Jolla Alcohol Research
2011
University of California, San Diego
2011
Institut de Biologie et Technologies
2007-2008
Commissariat à l'Énergie Atomique et aux Énergies Alternatives
2006-2008
CEA Paris-Saclay
2006
Stress Protector During prolonged fasting, the oxidation of fatty acids leads to increased accumulation d -β-hydroxybutyrate (βOHB) in bloodstream. Such concentrations βOHB inhibit class I histone deacetylases. Histone acetylation turn influences transcriptional activity at various genes. Shimazu et al. (p. 211 , published online 6 December; see Perspective by Sassone-Corsi ) found that among genes showing transcription animals treated with high were two implicated cellular responses...
Blood-brain barrier disruption, microglial activation and neurodegeneration are hallmarks of multiple sclerosis. However, the initial triggers that activate innate immune responses their role in axonal damage remain unknown. Here we show blood protein fibrinogen induces rapid toward vasculature is required for neuroinflammation. Using vivo two-photon microscopy, demonstrate microglia form perivascular clusters before myelin loss or paralysis onset that, plasma proteins, specifically...
Protein thiol oxidation subserves important biological functions and constitutes a sequel of reactive oxygen species toxicity. We developed two distinct thiol-labeling approaches to identify oxidized cytoplasmic protein thiols in Saccharomyces cerevisiae. Inone approach, we used N-(6-(biotinamido)hexyl)-3'-(2'-pyridyldithio)-propionamide purify thiols, the other, N-[(14)C]ethylmaleimide quantify this oxidation. Both showed large number same proteins with ( approximately 200), 64 which were...
Multiple sclerosis (MS) is an autoimmune disease in which myelin progressively degraded. Because degraded may both initiate and accelerate progression, clearing from extracellular spaces be critical. In this study, we prepared vesicles (MV) rat brains as a model of myelin. Murine embryonic fibroblasts (MEFs) rapidly internalized MVs, accumulated lysosomes only when these cells expressed low-density lipoprotein receptor-related protein (LRP1). Receptor-associated (RAP), binds LRP1 inhibits...
Insulin resistance is a key factor in the etiology of type 2 diabetes. Insulin-stimulated glucose uptake mediated by transporter 4 (GLUT4), which expressed mainly skeletal muscle and adipose tissue. translocation GLUT4 from its intracellular compartment to plasma membrane regulated small guanosine triphosphate hydrolases (GTPases) essential for maintenance normal homeostasis. Here we show that p75 neurotrophin receptor (p75(NTR)) regulator insulin resistance. p75(NTR) knockout mice increased...
The heart exhibits the highest basal oxygen (O2) consumption per tissue mass of any organ in body and is uniquely dependent on aerobic metabolism to sustain contractile function. During acute hypoxic states, responds with a compensatory increase cardiac output that further increases myocardial O2 demand, predisposing ischemic stress dysfunction. Here, we test utility novel engineered protein derived from heme-based nitric oxide (NO)/oxygen (H-NOX) family bacterial proteins as an delivery...
Abstract Hypoxia-like tissue alterations, characterized by the upregulation of hypoxia-inducible factor-1α (HIF-1α), have been described in normal appearing white matter and pre-demyelinating lesions multiple sclerosis (MS) patients. As HIF-1α regulates transcription a wide set genes involved neuroprotection neuroinflammation, expression may contribute to pathogenesis inflammatory demyelination. To test this hypothesis, we analyzed effect cell-specific genetic ablation or overexpression on...
Tissue hypoxia plays a critical role in the events leading to cell death ischemic stroke. Despite promising results preclinical and small clinical pilot studies, inhaled oxygen supplementation has not translated improved outcomes large trials. Moreover, observations suggest that indiscriminate can adversely affect outcome, highlighting need develop novel approaches selectively deliver affected regions. This study tested hypothesis intravenous delivery of carrier (Omniox-Ischemic Stroke...
We have developed OMX-4.80, a tunable oxygen carrier from the H-NOX protein family, that preferentially accumulates in tumor tissue, reduces hypoxia and enhances radiotherapy (RT). Tumor is associated with poor patient outcomes multiple solid tumors including glioblastoma (GB) thought to be major contributor cancer responses chemo radiation therapy. Here, we show OMX-4.80 administered i.v. into tail vein of mice bearing orthotopic GB passes blood-tumor barrier, penetrates deep intracranial...
Dalcinonacog alfa (DalcA), a novel subcutaneously administered recombinant human factor IX (FIX) variant is being developed for adult and paediatric patients with hemophilia B (HB). DalcA has been shown to raise FIX clinically meaningful levels in adults HB. This work aimed support dosing regimen selection perform first-in-paediatric dose extrapolations using model-based pharmacokinetic (PK) approach. A population PK model was built data from two clinical trials (NCT03186677, NCT03995784)....
Abstract Oxygen is one of the key modulators tumor microenvironment whereby low oxygen or hypoxia associated with resistance to chemo- and radio- therapies poor patient outcomes. Hypoxia favors an immunosuppressive by promoting Treg recruitment activation suppressing T cell NK proliferation effector function pro-inflammatory cytokine secretion. Therefore, reversing could create immunopermissive improve efficacy several immunotherapies. Omniox has developed carrier OMX that can specifically...
Interspecies scaling of the pharmacokinetics (PK) CB 4332, a 150 kDa recombinant complement factor I protein, was performed using traditional and model-based approaches to inform first-in-human dose selection. Plasma concentration versus time data from four preclinical PK studies single intravenous subcutaneous (SC) 4332 dosing in mice, rats nonhuman primates (NHPs) were modeled simultaneously naive pooling including allometric scaling. The human-equivalent calculated no observed adverse...
Abstract BACKGROUND: Omniox has engineered OMX-4.80P, a PEGylated H-NOX oxygen carrier, as long-acting therapeutic candidate to enhance radiotherapy (RT) in the treatment of glioblastoma and other solid tumors. Here, we describe pre-clinical profile demonstrating it is well tolerated, long-lasting circulation tumors, penetrates deep into tumor tissue reducing hypoxia altering hypoxic phenotype by downregulating HIF-1 pathway. Furthermore, dramatically enhances RT leading cures. METHODS: We...