A5046961813- Malaria Research and Control
- Mosquito-borne diseases and control
- Chemokine receptors and signaling
- Cell Adhesion Molecules Research
- Research on Leishmaniasis Studies
- Invertebrate Immune Response Mechanisms
- Trypanosoma species research and implications
- HIV Research and Treatment
- Computational Drug Discovery Methods
- Complement system in diseases
- Immunodeficiency and Autoimmune Disorders
- Angiogenesis and VEGF in Cancer
- Immune Cell Function and Interaction
- Phagocytosis and Immune Regulation
- Cell death mechanisms and regulation
- Cancer-related Molecular Pathways
- Hepatitis B Virus Studies
- Pharmacogenetics and Drug Metabolism
- Retinoids in leukemia and cellular processes
- Proteoglycans and glycosaminoglycans research
- Kruppel-like factors research
- Burkholderia infections and melioidosis
- Neuroinflammation and Neurodegeneration Mechanisms
- Herpesvirus Infections and Treatments
- Microtubule and mitosis dynamics
Liverpool School of Tropical Medicine
2019-2024
Istituto Superiore di Sanità
2007-2019
Istituto Dermopatico dell'Immacolata
1999-2003
Istituti di Ricovero e Cura a Carattere Scientifico
2000-2003
University of Bari Aldo Moro
1997-2000
University of Siena
2000
Sapienza University of Rome
2000
University of L'Aquila
1995
A major cause of the paucity new starting points for drug discovery is lack interaction between academia and industry. Much global resource in biology present universities, whereas focus medicinal chemistry still largely within Open source discovery, with sharing information, clearly a first step towards overcoming this gap. But interface could especially be bridged through scale-up open physical compounds, which would accelerate finding discovery. The Medicines Malaria Venture Box...
Despite over a century of study malaria parasites, parts the Plasmodium falciparum life cycle remain virtually unknown. One these is early gametocyte stage, round shaped cell morphologically similar to an asexual trophozoite in which major cellular transformations ensure subsequent development elongated gametocyte. We developed protocol obtain for first time highly purified preparations gametocytes using transgenic line expressing green fluorescent protein from onset gametocytogenesis....
The asexual blood stages of Plasmodium falciparum cause the most lethal form human malaria. During growth within an infected red cell, parasite multiplication and formation invasive merozoites is called schizogony. Here, we present a detailed analysis phosphoproteome P. schizonts revealing 2541 unique phosphorylation sites, including 871 novel sites. Prominent roles for cAMP-dependent protein kinase A- phosphatidylinositol-signaling were identified following by functional enrichment,...
Primaquine (PQ) is an essential antimalarial drug but despite being developed over 70 years ago, its mode of action unclear. Here, we demonstrate that hydroxylated-PQ metabolites (OH-PQm) are responsible for efficacy against liver and sexual transmission stages Plasmodium falciparum. The activity PQ depends on host CYP2D6 status, whilst OH-PQm display direct, CYP2D6-independent, activity. requires hepatic metabolism to exert gametocyte stages. modest parasite gametocytes; however, potency...
Malaria parasites invade erythrocytes of their host both for asexual multiplication and differentiation to male female gametocytes - the precursor cells Plasmodium gametes. For further development parasite is dependent on efficient release daughter gametes from erythrocyte. How malarial exit remains largely unknown. We here report characterization a berghei protein that involved in egress Protein MDV-1/PEG3, like its falciparum orthologue, present sexes, but more abundant female, where it...
Summary Osmiophilic bodies are membrane‐bound vesicles, found predominantly in Plasmodium female gametocytes, that become progressively more abundant as the gametocyte reaches full maturity. These vesicles lie beneath subpellicular membrane of gametocyte, and release their contents into parasitophorous vacuole has been postulated to aid escape gametocytes from erythrocyte after ingestion by mosquito. Currently, only protein known be associated with osmiophilic falciparum is Pfg377, a...
New reliable and cost-effective antimalarial drug screening assays are urgently needed to identify drugs acting on different stages of the parasite Plasmodium falciparum, particularly those responsible for human-to-mosquito transmission, that is, P. falciparum gametocytes. Low Z' factors, narrow dynamic ranges, and/or extended assay times commonly reported in current gametocyte measuring gametocyte-expressed fluorescent or luciferase reporters, endogenous ATP levels, activity enzymes,...
As most available antimalarial drugs are ineffective against the Plasmodium falciparum transmission stages, new parasite's gametocytes urgently needed to combat malaria globally. The unique biology of requires assays that need be specific, faithfully monitor anti-gametocyte activity, and easy perform, cheap scalable high-throughput screening (HTS). We developed an HTS cell-based assay with P. specifically expressing a potent luciferase. To confirm hit activity for several parasite genotypes,...
In skeletal muscle differentiation, the retinoblastoma protein (pRb) is absolutely necessary to establish definitive mitotic arrest. It widely assumed that pRb equally essential sustain postmitotic state, but this contention has never been tested. Here, we show terminal proliferation arrest maintained in cells by a pRb-independent mechanism. Acute Rb excision from conditional knockout myotubes caused reexpression of E2F transcriptional activity, cyclin-E and -A kinase activities, PCNA, DNA...
Abstract Several chemokines have been shown to regulate cellular apoptosis following discrete stimuli. It was previously demonstrated that the CC chemokine CCL1 (I-309) rescues thymic lymphoma cells from apoptois by unknown mechanisms. The aim of our study characterize role receptor 8 (CCR8), only described for CCL1, in rescue murine and thymocytes dexamethasone (dex)-induced apoptosis. We show here CCR8-restricted agonist Kaposi sarcoma-associated herpesvirus-encoded viral...
The goal to prevent Plasmodium falciparum transmission from humans mosquitoes requires the identification of targetable metabolic processes in mature (stage V) gametocytes, sexual stages circulating bloodstream. This task is complicated by apparently low metabolism these cells, which renders them refractory most antimalarial inhibitors and constrains development specific sensitive cell-based assays. Here, we identify functionally characterize regulatory regions P. gene PF3D7_1234700,...
Summary In the human malaria parasite Plasmodium falciparum , gametocyte maturation is a process remarkably longer than in other species, accompanied by expression of 2–300 sexual stage‐specific proteins. Disruption several their encoding genes so far showed that only abundant protein Pfg27, produced at onset differentiation, essential for production. contrast with what has been previously described, here we show P. pfg27 disruptant lines are able to undergo all stages maturation, and mature...
ABSTRACT Several herpesviruses contain open reading frames (ORFs) that encode potential homologs of eucaryotic genes. Equine herpesvirus 2 (EHV-2) is a gammaherpesvirus related to other lymphotropic such as saimiri and Epstein-Barr virus. The E1 ORF EHV-2, G protein-coupled receptor homolog, shows 31 47% amino acid identity with known CC chemokine receptors. To investigate whether may functional receptor, we cloned the expressed it in stably transfected cell lines. We report here...
The Plasmodium subtilisin-like serine protease SUB1 is expressed in hepatic and both asexual sexual blood parasite stages. required for egress of invasive forms the from erythrocytes hepatocytes, but its subcellular localisation, function, potential substrates stages are unknown. Here, we have characterised expression profile localisation berghei We show that selectively mature male gametocytes localises to secretory organelles known be involved gamete egress, called osmiophilic bodies....
SUMMARY IL-6 is a growth factor which interferes in the apoptosis of malignant plasma cells. Here we explore its role spontaneous and Fas/FasL-regulated seven myeloma cell clones (MCC). MCC-2 -7 were constitutively defective Fas antigen presence large membrane exposure FasL, showed high rate proliferation irrespective IL-6. Cytofluorimetric analysis following propidium iodide (PI) staining revealed minimal extent apoptosis, as other IL-6-insensitive, though Fas-positive MCC, namely MCC-3 -5....
Abstract A hallmark of cerebral malaria (CM) is sequestration Plasmodium falciparum infected erythrocytes (IE) within the brain microvasculature. Binding IE to endothelium reduces microvascular flow and combined with an inflammatory response perturbs endothelial barrier function, resulting in breakdown blood- (BBB). Cytoadherence leads activation alters a range cell processes affecting signalling pathways, receptor expression, coagulation, disruption BBB integrity. Here, we investigated...
ABSTRACT A hallmark of cerebral malaria (CM) is sequestration Plasmodium falciparum -infected erythrocytes (IE) within the brain microvasculature. Binding IE to endothelium reduces microvascular flow and, combined with an inflammatory response, perturbs endothelial barrier function, resulting in breakdown blood-brain (BBB). Cytoadherence leads activation and alters a range cell processes affecting signaling pathways, receptor expression, coagulation, disruption BBB integrity. Here, we...
Monocytes contribute to the pro-inflammatory immune response during blood stage of a Plasmodium falciparum infection, but their precise role in malaria pathology is not clear. Besides phagocytosis, monocytes are activated by products from P . infected erythrocytes (IE) and one activation pathways potentially NLR family pyrin domain containing 3 (NLRP3) inflammasome, multi-protein complex that leads production interleukin (IL)-1β. In cerebral cases, accumulate at IE sequestration sites brain...