A5022265137- Cellular transport and secretion
- Alzheimer's disease research and treatments
- Amyloidosis: Diagnosis, Treatment, Outcomes
- Pluripotent Stem Cells Research
- Endoplasmic Reticulum Stress and Disease
- Autoimmune and Inflammatory Disorders Research
- Dermatological and Skeletal Disorders
- Genetics, Aging, and Longevity in Model Organisms
- Pancreatic function and diabetes
- Lysosomal Storage Disorders Research
- Inflammatory Myopathies and Dermatomyositis
- Immune Cell Function and Interaction
- Immunodeficiency and Autoimmune Disorders
- Signaling Pathways in Disease
- Polyomavirus and related diseases
- Animal testing and alternatives
- Biosensors and Analytical Detection
- Phagocytosis and Immune Regulation
- Neonatal Respiratory Health Research
- Inhalation and Respiratory Drug Delivery
- Hereditary Neurological Disorders
- Prion Diseases and Protein Misfolding
- Science, Research, and Medicine
- RNA and protein synthesis mechanisms
- T-cell and B-cell Immunology
General Atomics (United States)
2024
Abreos Biosciences (United States)
2022-2024
E Ink (South Korea)
2022
Predictive Biology (United States)
2016
Scripps Research Institute
2001-2013
The Honourable Society of Lincoln's Inn
1998-2001
MRC Laboratory for Molecular Cell Biology
2000
University College London
1998-2000
University of Cambridge
1995-1999
Addenbrooke's Hospital
1995
There are two clathrin-coated vesicle adaptor complexes in the cell, one associated with plasma membrane and TGN. The subunit composition of complex is alpha-adaptin, beta-adaptin, AP50, AP17; while that TGN gamma-adaptin, beta'-adaptin, AP47, AP19. To search for targeting signals, we have constructed chimeras between alpha-adaptin gamma-adaptin within their NH2-terminal domains. We identified stretches sequence proteins amino acids approximately 130 330-350 essential targeting....
The AP-1 adaptor complex is associated with the TGN, where it links selected membrane proteins to clathrin lattice, enabling these be concentrated in clathrin-coated vesicles. To identify other that participate vesicle cycle at we have carried out a yeast two- hybrid library screen using γ-adaptin subunit of as bait. Two novel, ubiquitously expressed were found: p34, which interacts both and α-adaptin, γ-synergin, an alternatively spliced protein apparent molecular mass ∼110–190 kD, only...
Homotypic fusion of immature secretory granules (ISGs) gives rise to mature (MSGs), the storage compartment in endocrine and neuroendocrine cells for hormones neuropeptides. With use a cell-free assay, we investigated which soluble N-ethylmaleimide-sensitive protein attachment receptor (SNARE) molecules are involved homotypic ISGs. Interestingly, SNARE mediating exocytosis MSGs cells, syntaxin 1, SNAP-25, VAMP2, were not ISG fusion. Instead, have identified 6 as component core machinery...
The lytic proteins mediating target cell killing are stored in the lysosomes of activated cytotoxic T lymphocytes (CTL) and secreted upon recognition a cell. These secretory cannot be detected resting lymphocytes. Interaction with activates de novo formation lysosomes. CTL clones culture mimic this behaviour, so provide an ideal system for studying lysosome biogenesis maturation. In genetic disease, Chediak Higashi syndrome (CHS), all cells enlarged reduced number compared wild‐type (WT)...
Proteostasis is critical for maintaining cell function and proteome stability may play an important role in human embryonic stem (hESC) immortality. Notably, hESC populations exhibit a high assembly of active proteasomes, key node the proteostasis network. FOXO4, insulin/IGF-1 responsive transcription factor, regulates proteasome activity hESCs. We find that loss FOXO4 reduces potential hESCs to differentiate into neural lineages. Therefore, crosses evolutionary boundaries links invertebrate...
The biogenesis of secretory granules embodies several morphological and biochemical changes. In particular, in neuroendocrine cells maturation is characterized by an increase size which has been proposed to reflect homotypic fusion immature (ISGs). Here we describe assay that provides the first evidence for such a event allows us analyze its regulation. reconstitutes between one population ISGs containing [35S]sulfate-labeled substrate, secretogranin II (SgII), second prohormone convertase...
Familial amyloidosis of Finnish type (FAF) is a systemic amyloid disease associated with the deposition proteolytic fragments mutant (D187N/Y) plasma gelsolin. We report mouse model FAF featuring muscle-specific promoter to drive D187N gelsolin synthesis. This recapitulates aberrant endoproteolytic cascade and aging-associated extracellular FAF. Amyloidogenesis observed only in tissues synthesizing human gelsolin, despite presence full-length its 68-kDa cleavage product blood—demonstrating...
The importance of easily accessible, noninvasive samples, such as saliva, to effectively monitor serum antibody levels has been underscored by the SARS-CoV-2 (COVID-19) pandemic. Although a correlation between saliva and titers observed, ability predict from measurements in is not well established. Herein, authors demonstrate that both nasal specimens can be used accurately determine utilizing endogenous total IgG an internal calibrator. They postulate this method extended measurement many...
Sporadic inclusion body myositis has a significant impact on the life of elderly. Despite some similarities to other myopathies with established genetic defects, little is known about mechanisms its development and no effective treatment available. Therefore, there need for animal models that can faithfully reconstitute important aspects this human disease. The authors recently expressed mutant form gelsolin in mice under control muscle-specific promoter. This induced myopathic changes...
Natalizumab, a therapeutic antibody used to treat multiple sclerosis, undergoes in vivo Fab arm exchange form monovalent bispecific antibody. Although highly efficacious, the immunosuppressive activity of natalizumab has been associated with JC polyomavirus-driven progressive multifocal leukoencephalopathy (PML). Development assays that can distinguish between and quantify bivalent (unexchanged) (exchanged) forms clinical samples may be useful for optimizing extended interval dosing reducing...