A5036655124- Cellular transport and secretion
- Retinal Diseases and Treatments
- Retinal Development and Disorders
- Platelet Disorders and Treatments
- Blood Coagulation and Thrombosis Mechanisms
- Mosquito-borne diseases and control
- Autophagy in Disease and Therapy
- Complement system in diseases
- Lipid Membrane Structure and Behavior
- Toxoplasma gondii Research Studies
- Blood properties and coagulation
- Calcium signaling and nucleotide metabolism
- Hepatitis B Virus Studies
- Cell Adhesion Molecules Research
- Endoplasmic Reticulum Stress and Disease
- Pineapple and bromelain studies
- Parkinson's Disease Mechanisms and Treatments
- Genetic Neurodegenerative Diseases
- Electrospun Nanofibers in Biomedical Applications
- Mast cells and histamine
- melanin and skin pigmentation
- Retinopathy of Prematurity Studies
- Erythrocyte Function and Pathophysiology
- Alzheimer's disease research and treatments
- Connective tissue disorders research
Universidade Nova de Lisboa
2012-2023
MRC Laboratory for Molecular Cell Biology
2016-2022
University College London
2013-2022
Instituto Gulbenkian de Ciência
2012-2015
Imperial College London
2012-2013
Autophagy plays an important role in the defence against intracellular pathogens. However, some microorganisms can manipulate this host cell pathway to their advantage. In study, we addressed of autophagy during Plasmodium berghei liver infection. We show that vesicles containing autophagic marker LC3 surround parasites from early time-points after invasion and throughout infection colocalize with parasitophorous vacuole membrane. Moreover, LC3-positive are amphisomes converge endocytic...
The retinal pigment epithelium (RPE) is a pigmented monolayer of cells lying between the photoreceptors and layer fenestrated capillaries, choriocapillaris. Choroideremia (CHM) an X-linked progressive degeneration these three layers caused by loss function Rab Escort protein-1 (REP1). REP1 involved in prenylation proteins, key regulators membrane trafficking. To study pathological consequences chronic disruption traffic RPE we used cell type-specific knock-out mouse model disease, where...
Abstract Previously, we found that age‐dependent accumulation of beta‐amyloid is not sufficient to cause synaptic decline. Late‐endocytic organelles (LEOs) may be driving decline as lysosomes (Lys) are a target cellular aging and relevant for synapses. We LAMP1‐positive LEOs increased in size number accumulated near synapses aged neurons brains. LEOs' distal might relate the anterograde movement neurons. Dissecting LEOs, late‐endosomes while there fewer terminal Lys neurites, but cell body....
The obligate intracellular liver stage of the Plasmodium parasite represents a bottleneck in life cycle and remains promising target for therapeutic intervention. During this stage, parasites undergo dramatic morphological changes achieve one fastest replication rates among eukaryotic species. Nevertheless, relatively little is known about interactions with host hepatocyte. Using immunofluorescence, live cell imaging electron microscopy, we show that berghei are surrounded by vesicles from...
Essentials Endothelial activation initiates multiple processes, including hemostasis and inflammation. The molecules that contribute to these processes are co-stored in secretory granules. How can the cells control release of granule content allow differentiated responses? Selected agonists recruit an exocytosis-linked actin ring boost a subset cargo.Background harbor specialized storage organelles, Weibel-Palade bodies (WPBs). Exocytosis WPB into vascular lumen primary hemostasis, mediated...
Changes in the size of cellular organelles are often linked to modifications their function. Endothelial cells store von Willebrand Factor (vWF), a glycoprotein essential haemostasis Weibel-Palade bodies (WPBs), cigar-shaped secretory granules that generated wide range sizes. We recently showed forcing changes WPBs modifies activity this cargo. now find endothelial treated with statins produce shorter and vWF they release at exocytosis displays reduced capability recruit platelets cell...
Highlights•The Arf-GEF GBF1 modulates anterograde trafficking of VWF and ECM proteins•Loss slows ER TGN exit, producing swollen giant WPBs•Activation via AMPK reduces endothelial WPB size secretion•Metabolic change alters cargo secretion AMPK-GBF1SummaryHow can membrane be modulated by physiological cues? A screen Golgi-associated proteins revealed that the ARF-GEF selectively modulate ER-Golgi prohaemostatic von Willebrand factor (VWF) extracellular matrix (ECM) in human cells mouse...
Parkinson's Disease (PD) is a common neurodegenerative disorder affecting millions of people worldwide for which there are only symptomatic therapies. Small molecules able to target key pathological processes in PD have emerged as interesting options modifying disease progression. We previously shown that (poly)phenol-enriched fraction (PEF) Corema album L. leaf extract modulates central events pathogenesis, namely α-synuclein (αSyn) toxicity, aggregation and clearance. PEF was now subjected...
Malaria parasites go through an obligatory liver stage before they infect erythrocytes and cause disease symptoms. In the host hepatocytes, parasite is enclosed by a parasitophorous vacuole membrane (PVM). Here, we dissected interaction between Plasmodium cell late endocytic pathway show that growth dependent on phosphoinositide 5-kinase (PIKfyve) converts phosphatidylinositol 3-phosphate [PI(3)P] into 3,5-bisphosphate [PI(3,5)P2 ] in endosomal system. We found inhibition of PIKfyve either...
Weibel-Palade bodies (WPBs) are endothelial storage organelles that mediate the release of molecules involved in thrombosis, inflammation and angiogenesis, including pro-thrombotic glycoprotein von Willebrand factor (VWF). Although many protein components required for WPB formation function have been identified, role lipids is almost unknown. We examined two key phosphatidylinositol kinases control 4-phosphate levels at trans-Golgi network, site biogenesis. RNA interference type II 4-kinases...
Purpose: We aim to characterize the pathways required for autofluorescent granule (AFG) formation by RPE cells using cultured monolayers. Methods: fed monolayers in culture with a single pulse of photoreceptor outer segments (POS). After 24 hours started accumulating AFGs that were comparable lipofuscin vivo. Using this model, we used variety light and electron microscopical techniques, flow cytometry Western blot analyze AFGs. also generated mutant line lacking cathepsin D gene editing....
In vertebrate cells, the Golgi functional subunits, mini-stacks, are linked into a tri-dimensional network. How this "ribbon" architecture relates to functions remains unclear. Are all connections between mini-stacks equal? Is local structure of ribbon importance? These difficult questions address, without quantifiable readout output ribbon-embedded mini-stacks. Endothelial cells produce secretory granules, Weibel-Palade bodies (WPB), whose von Willebrand Factor (VWF) cargo is central...
Introduction Diabetes is one of the major metabolic diseases worldwide. Despite being a complex systemic pathology, aggregation and deposition Islet Amyloid Polypeptide (IAPP), or amylin, recognized histopathological marker disease. Although IAPP proteotoxicity represents an important trigger β-cell dysfunction ultimately death, its exploitation as therapeutic tool remains underdeveloped. The bioactivity (poly)phenols towards inhibition pathological protein well known, however, most...
Age-related macular degeneration (AMD) is the most common blinding disease in western world and currently incurable. Although exact causes of AMD are not clear, primary origin pathology appears to be retinal pigment epithelium (RPE). RPE responsible for daily digestion photoreceptor outer segments (POS), which imposes a heavy continuous burden on lysosomal network. POS feeding assay vitro suggested that accumulation autofluorescence granules (AFG), similar lipofuscin vivo, derives from...
Myotonic dystrophy type 1 (DM1) is an autosomal dominant disease caused by a CTG repeat expansion in the 3′ untranslated region of dystrophia myotonica protein kinase gene. AKT dephosphorylation and autophagy are associated with DM1. Autophagy has been widely studied DM1, although endocytic pathway not. critical role endocytosis, its phosphorylation mediated activation tyrosine receptors, such as epidermal growth factor receptor (EGFR). EGF-activated EGFR triggers internalization degradation...
Abstract Purpose We aim to characterize the pathways required for autofluorescent granule (AFG) formation by retinal pigment epithelium (RPE) cells using cultured monolayers. Methods fed RPE monolayers in culture with a single pulse of photoreceptor outer segments (POS). After 24h started accumulating AFGs similar lipofuscin vivo . Using this model, we used variety light and electron microscopical techniques, flow cytometry western blot analyze AFGs. also generated mutant line lacking...