- Mosquito-borne diseases and control
- Malaria Research and Control
- Cell Adhesion Molecules Research
- Glycosylation and Glycoproteins Research
- Proteoglycans and glycosaminoglycans research
- Insect symbiosis and bacterial influences
- Cancer Immunotherapy and Biomarkers
- Insect Resistance and Genetics
- CAR-T cell therapy research
- Vector-borne infectious diseases
- Corneal surgery and disorders
- Hedgehog Signaling Pathway Studies
- Melanoma and MAPK Pathways
- Cutaneous Melanoma Detection and Management
- TGF-β signaling in diseases
- Bacterial Identification and Susceptibility Testing
- Electrolyte and hormonal disorders
- Insect and Pesticide Research
- Fibroblast Growth Factor Research
- T-cell and B-cell Immunology
- Corneal Surgery and Treatments
- Dengue and Mosquito Control Research
- Genetic diversity and population structure
- Immunotherapy and Immune Responses
- Cancer-related Molecular Pathways
Wellcome Sanger Institute
2023-2025
Kenya Medical Research Institute
2024
Pwani University
2024
International Centre of Insect Physiology and Ecology
2024
Smithsonian Tropical Research Institute
2018-2021
Instituto de Investigaciones Científicas y Servicios de Alta Tecnología
2020
University of Manchester
2015-2018
Bristol-Myers Squibb (United States)
1996-2017
Bristol-Myers Squibb (Germany)
1992-2013
Office of Adolescent Health
2011
Transforming growth factor-beta (TGF-beta) is capable of affecting the proliferation many cell types. To identify novel genes whose protein products may mediate cellular responses to this factor, a cDNA library was made from mRNA isolated human lung adenocarcinoma line (A549) that had been treated for 3 days with TGF-beta. The screened by differential hybridization and clone, beta ig-h3, isolated. This gene induced up 20-fold in A549 cells after 2 treatment TGF-beta 1. It also several other...
Glycosaminoglycan-modified isoforms of CD44 have been implicated in growth factor presentation at sites inflammation. In the present study we show that COS cell transfectants expressing containing alternatively spliced exon V3 are modified with heparan sulfate (HS). Binding studies three HS-binding factors, basic-fibroblast (b-FGF), heparin binding-epidermal (HB-EGF), and amphiregulin, showed HS-modified able to bind b-FGF HB-EGF, but not AR. HB-EGF binding was eliminated by pretreating...
βig-h3 is a novel gene first discovered by differential screening of cDNA library made from A549 human lung adenocarcinoma cells treated with transforming growth factor-βl (TGF-β1). It encodes 683-aminoacid protein containing secretory signal sequence and four homologous internal domains. Here we show that treatment several types cells, including melanoma mammary epithelial keratinocytes, fibroblasts, TGF-β resulted in significant increase RNA. A portion the coding was expressed bacteria,...
The hyaluronan (HA)-binding function (lectin function) of the leukocyte homing receptor, CD44, is tightly regulated. Herein we address possible mechanisms that regulate CD44 isoform-specific HA binding. Binding studies with melanoma transfectants expressing CD44H, CD44E, or soluble immunoglobulin fusions CD44H and CD44E (CD44H-Rg, CD44E-Rg) showed although both isoforms can bind HA, binds more efficiently than CD44E. Using CD44-Rg fusion proteins show variably spliced exons in V8-V10,...
The long-distance dispersal of the invasive disease vectors Aedes aegypti and albopictus has introduced arthropod-borne viruses into new geographical regions, causing a significant medical economic burden. used-tire industry is an effective means dispersal, yet studies to determine occurrence factors influencing their distribution along local transport networks are lacking. To assess infestation primary network Panama we documented all existing garages that trade used tires on highway...
Abstract Aedes aegypti and albopictus develop in the same aquatic sites where they encounter microorganisms that influence their life history capacity to transmit human arboviruses. Some bacteria such as Wolbachia are currently being considered for control of Dengue, Chikungunya Zika. Yet little is known about dynamics diversity -associated bacteria, including larval habitat features shape tempo-spatial distribution. We applied large-scale 16S rRNA amplicon sequencing 960 adults larvae both...
Anopheles coluzzii is a primary vector of malaria found in West and Central Africa, but its presence has hitherto never been documented Kenya. A thorough understanding bionomics important as it enables the implementation targeted effective control interventions. Malaria surveillance efforts country have tended to focus on historically known vectors. The current study sought determine taxonomic status samples collected from five different epidemiological zones Kenya well describe population...
ABSTRACT Anopheles mosquitoes are major malaria vectors, encompassing several species complexes with diverse life histories, transmission risks and insecticide resistance profiles that challenge control efforts. This study investigated the genetic structure of gambiae complex in Tanzania. We analysed whole‐genome sequence data 300 collected between 2012 2015 across four regions northern Tanzania identified An. s.s., arabiensis a distinct taxonomic group was previously unknown. taxon has...
CTLA-4 (CD152), high-avidity receptor for CD80 and CD86, is a powerful regulator of T cell activation. While functions at the surface, it primarily localized in intracellular vesicles cycles to surface. The cytoplasmic domain contains sequences that direct its localization regulate signaling. Here we demonstrate effector molecules involved trafficking signaling interact with distinct, but overlapping, domain. Using yeast two-hybrid method, association mu2 subunit AP-2, clathrin-associated...
Abstract Transforming growth factor–β (TGF-β) plays an important role in vascular lesion formation and possibly the renarrowing process (“restenosis”) that occurs after balloon angioplasty. Secreted a latent form by most cells, TGF-β requires enzymatic conversion before it is biologically active. TGF-β–inducible gene h3 (βig-h3) novel molecule induced when cells are treated with TGF-β1. This study examined expression of βig-h3 normal diseased human tissue. To determine pattern arteries,...
Increasing globalization has promoted the spread of exotic species, including disease vectors. Understanding evolutionary processes involved in such colonizations is both intrinsic biological interest and important to predict mitigate future risks. The Aedes aegypti mosquito a major vector dengue, chikungunya Zika, worldwide which been facilitated by Ae. aegypti's adaption human-modified environments. this invasion requires characterization genetic make-up source population(s). application...
Local adaptation is important when predicting arthropod-borne disease risk because of its impacts on vector population fitness and persistence. However, the extent that populations are adapted to environment generally remains unknown. Despite low structure high gene flow in
ABSTRACT CD44 is a polymorphic cell surface glycoprotein, currently proposed to be the principal receptor for hyaluronan. However, different isoforms of CD44, expressed in human lymphoid tumor cells, appear have distinct effects on ability cells attach hyaluronan-coated surfaces and their capacity form tumors vivo. In present study, we address mechanisms that may regulate isoform-dependent adhesion We use Burkitt lymphoma, stably transfected with six alternatively spliced isoforms, determine...
Isoforms of CD44 are differentially modified by the glycosaminoglycans (GAGs) chondroitin sulfate (CS), heparan (HS), and keratan sulfate. GAG assembly occurs at serines followed glycines (SG), but not all SG utilized. Seven motifs distributed in five exons, this paper we identify HS CS sites that utilized CD44. Not modified. The SGSG motif exon V3 is only site; site also with CS. attachment was eliminated mutation to alanine (AGAG). Exon E5 other supports Using a number recombinant protein...
DCC (deleted incolorectal carcinoma) is a broadly expressed cell-surface receptor. Netrin-1 was recently identified as ligand in brain, but the possibility of other ligands suggested by finding that an anti-DCC antibody (clone AF5) neutralized netrin-1-dependent commissural axon outgrowth without blocking DCC/netrin-1 interactions. Here we have searched for alternative ligands. A DCC-Ig fusion protein bound to neural and epithelial derived cell lines, indicating these lines express ligand(s)...
Despite an increase in dengue outbreaks and the arrival of chikungunya Zika disease Panama, studies on demographic history invasive Aedes mosquitoes that are principle vectors these diseases still lacking this region. Here, we assess genetic diversity order to decipher their invasion histories into Isthmus Panama. DNA sequences from mitochondrial cytochrome C oxidase I gene obtained 30 localities 10 provinces confirmed presence more than one haplogroup (i.e., maternal lineage) each species....
The two main Afrotropical malaria vectors - Anopheles coluzzii and An. gambiae are genetically distinct reproductively isolated across West Africa. However, populations at the western extreme of their range assigned as "intermediate" between species by whole genome sequence (WGS) data, hybrid forms conventional molecular diagnostics. By exploiting WGS data from 1190 specimens collected west Africa via 1000 Genomes network, we identified a putative taxon in far-west (provisionally named...
Background and Purpose: The objective of this project was to assess the safety mobilizing patients with femoral arterial hemodialysis (HD) catheters in intensive care unit (ICU). These had previously been perceived as barriers mobility at our institution, restricting these bed-rest. Approach: An interprofessional team developed a protocol for mobilization HD catheters. A prospective review conducted 3 ICUs. Patients were mobilized maximal level monitored adverse events. Outcomes:...
PurposeDeposition of abnormal sub-epithelial matrix and posterior collagenous layer by epithelium endothelium, respectively, in Fuchs' dystrophy gives us the opportunity to determine if these tissues synthesize βig-h3.MethodsImmunohisto-/immunocytochemistry corneas were conducted with rabbit anti-human βig-h3 monoclonal type VI collagen. Labeled sense anti-sense oligonucleotide probes used for situ hybridization.Resultsβig-h3-specific fluorescence was found just beneath detached matrix,...
Adult emergence at the end of metamorphosis in moth Manduca sexta is followed by death abdominal interneurons and motoneurons. Abdominal ganglia removed from insects before this period naturally occurring cell maintained vitro showed neuronal confined to same cells that normally die vivo. Addition physiological levels steroid 20-hydroxyecdysone culture system prevented selective these
A total of 276 blood culture bottles with Staphylococcus aureus were tested by direct cefoxitin disk diffusion testing; 105 (38.1%) had zone sizes </=17 mm (all methicillin-resistant S. [MRSA]), 18 (6.5%) that measured (17 MRSA and 1 methicillin-susceptible [MSSA]), 8 (2.9%) 19 (6 2 MSSA), 20 137 (49.6%) >/=21 MSSA). Detection MRSA/MSSA in cultures could be reported 10 to 24 h earlier for 88% accuracy.