A5032744956- Asthma and respiratory diseases
- RNA Research and Splicing
- Nuclear Structure and Function
- Ubiquitin and proteasome pathways
- Chronic Obstructive Pulmonary Disease (COPD) Research
- Allergic Rhinitis and Sensitization
- Pancreatic function and diabetes
- Bone and Dental Protein Studies
- Pediatric health and respiratory diseases
- Protein Degradation and Inhibitors
- Alkaline Phosphatase Research Studies
- Nitrogen and Sulfur Effects on Brassica
- Genomics and Chromatin Dynamics
- Polyamine Metabolism and Applications
- Immune Cell Function and Interaction
- Genomics, phytochemicals, and oxidative stress
- Glutathione Transferases and Polymorphisms
- Peptidase Inhibition and Analysis
- DNA Repair Mechanisms
- Tissue Engineering and Regenerative Medicine
- Transgenic Plants and Applications
AstraZeneca (Sweden)
2017-2024
Johns Hopkins University
2008-2016
Johns Hopkins Medicine
2016
University of Baltimore
2015
Proteins establish and maintain a distinct intracellular localization by means of targeting, retention, retrieval signals, ensuring most proteins reside predominantly in one cellular location. The enzymes involved the maturation lamin A present challenge to this paradigm. Lamin is first synthesized as 74-kDa precursor, prelamin A, with C-terminal CaaX motif undergoes series posttranslational modifications including processing (farnesylation, aaX cleavage carboxylmethylation), followed...
The proteolytic maturation of the nuclear protein lamin A by zinc metalloprotease ZMPSTE24 is critical for human health. precursor, prelamin A, undergoes a multi-step process that includes CAAX processing (farnesylation, proteolysis and carboxylmethylation C-terminal motif), followed ZMPSTE24-mediated cleavage last 15 amino acids, including modified C-terminus. Failure to cleave "tail", due mutations in either or ZMPSTE24, results permanently prenylated form underlies premature aging disease...
Abstract NK cell maturation is critical for normal effector function and the innate immune response to tumors pathogens. However, molecular pathways that control remain largely undefined. In this article, we investigate role of SPPL3, an intramembrane aspartyl protease, in murine biology. We find deletion SPPL3 hematopoietic system reduces numbers peripheral cells, clearance MHC class I–deficient vivo, cytotoxicity against tumor cells vitro. This phenotype concomitant with reduced...
Thymic stromal lymphopoietin (TSLP) is an epithelial-derived pro-inflammatory cytokine involved in the development of asthma and other atopic diseases. We used Bicycle Therapeutics' proprietary phage display platform to identify bicyclic peptides (Bicycles) with high affinity for TSLP, a target that difficult drug conventional small molecules due extended protein–protein interactions it forms both receptors. The hit series was shown bind TSLP hotspot, also by IL-7Rα. Guided first X-ray...
Oxidative stress in the human lung is caused by both internal (e.g., inflammation) and external stressors (smoking, pollution, infection) to drive pathology a number of diseases. Cellular damage oxidative reversed several pathways, one which antioxidant response. This response regulated transcriptional factor NRF2, has ability regulate transcription more than 250 genes. In disease, this balance overwhelmed, cells are unable return homeostasis. Several pharmacological approaches aim improve...
Background One-third of patients with Chronic obstructive pulmonary disease (COPD) have an eosinophilic inflammatory phenotype. Benralizumab is afucosylated humanised monoclonal antibody that targets the IL-5 receptor α subunit, leading to rapid and near-complete eosinophil depletion via antibody-dependent cellular cytotoxicity. We hypothesized benralizumab targeted immune modulation could impact on airway microbiome in COPD. Objective To investigate effect treatment inflammation sputum...
Abstract Natural killer (NK) cells play an essential role in tumor surveillance through direct cell lysis. Signal peptide peptidase-like 3 (SPPL3) is a highly conserved intramembrane aspartyl protease, but very little known about its functions vivo. We developed SPPL3 conditional knockout mouse and found that deletion of within the hematopoietic system using Vav1-iCre resulted peripheral defect NK number. The reduced population was hypofunctional clearance vivo lysis vitro. Analysis...
<b>Rational:</b> AZD9898 is a small molecule inhibitor of leukotriene C4 synthase (LTC4S) in development for oral treatment driven asthma. expected to inhibit the downstream production CysLTs but, unlike 5-LO Zileuton, spare LTB4 and pro-resolving lipoxins. Hence, has potential give additional benefits asthma compared modifiers on market. Here we describe pharmacological properties AZD9898. <b>Methods:</b> The PK/PD potency LTC4S was tested <i>in vivo</i> rat vitro</i> recombinant enzyme...