A5038959534- Immune cells in cancer
- Genomics and Rare Diseases
- Cytomegalovirus and herpesvirus research
- Immune Response and Inflammation
- Glycosylation and Glycoproteins Research
- Neurogenetic and Muscular Disorders Research
- Cancer-related molecular mechanisms research
- interferon and immune responses
- Immunotherapy and Immune Responses
- Chemokine receptors and signaling
- Asthma and respiratory diseases
- Genetics and Neurodevelopmental Disorders
- Neuroinflammation and Neurodegeneration Mechanisms
- Cellular transport and secretion
- Axon Guidance and Neuronal Signaling
- RNA regulation and disease
- Effects of Environmental Stressors on Livestock
- RNA Research and Splicing
- Antimicrobial Peptides and Activities
- Plant and animal studies
- Veterinary Equine Medical Research
- Insect and Pesticide Research
- Lysosomal Storage Disorders Research
- Insect and Arachnid Ecology and Behavior
- Retinal Development and Disorders
Roslin Institute
2016-2025
University of Pennsylvania
2023-2024
Vanderbilt University Medical Center
2024
University of Edinburgh
2016-2023
Telethon Institute Of Genetics And Medicine
2023
University of Campania "Luigi Vanvitelli"
2023
Harvard University
2023
Children's Hospital of Philadelphia
2023
Gdańsk Medical University
2023
University of Alabama at Birmingham
2022
Abstract The proliferation, differentiation and survival of mononuclear phagocytes depend on signals from the receptor for macrophage colony-stimulating factor, CSF1R. mammalian Csf1r locus contains a highly conserved super-enhancer, fms -intronic regulatory element (FIRE). Here we show that genomic deletion FIRE in mice selectively impacts CSF1R expression tissue development specific tissues. Deletion ablates murine embryonic stem cells. ΔFIRE/ΔFIRE lack macrophages embryo, brain microglia...
We have produced Csf1r-deficient rats by homologous recombination in embryonic stem cells. Consistent with the role of Csf1r macrophage differentiation, there was a loss peripheral blood monocytes, microglia brain, epidermal Langerhans cells, splenic marginal zone macrophages, bone-associated macrophages and osteoclasts, peritoneal macrophages. Macrophages red pulp, liver, lung, gut were less affected. The pleiotropic impacts on development multiple organ systems distinct from those reported...
The F4/80 antigen, encoded by the Adgre1 locus, has been widely-used as a monocyte-macrophage marker in mice, but its value macrophage other species is unclear, and even questioned. ADGRE1 seven transmembrane G protein-coupled receptor with an extracellular domain containing repeated Epidermal Growth Factor (EGF)-like calcium binding domains. Using new monoclonal antibody, we demonstrated that myeloid differentiation pigs, absent from progenitors bone marrow, highly-expressed mature...
Abstract CSF1 is the primary growth factor controlling macrophage numbers, but whether expression of receptor differs between discrete populations mononuclear phagocytes remains unclear. We have generated a Csf1r-mApple transgenic fluorescent reporter mouse that, in combination with lineage tracing, Alexa Fluor 647–labeled CSF1-Fc and CSF1, modified ΔCsf1–enhanced cyan protein (ECFP) transgene that lacks 150 bp segment distal promoter, we used to dissect differentiation responsiveness...
The genomes of RNA and small DNA viruses vertebrates display significant suppression CpG dinucleotide frequencies. Artificially increasing frequencies results in substantial attenuation virus replication, suggesting that these compositional changes may facilitate recognition non-self sequences. Recently, the interferon inducible protein ZAP, was identified as host factor responsible for sensing viral RNA, through direct binding possibly downstream targeting degradation. Using an arrayed...
Plasmacytoid dendritic cells (pDCs) are an important source of IFN-α/β in response to a variety viruses vivo, including murine cytomegalovirus (MCMV). However, the respective contributions various infected organs, and within these pDCs, conventional other cells, systemic production or innate cytokines during viral infections vivo is largely unknown. Whether specialization pDC subsets different patterns exists infection has not been investigated. Here, by analyzing for first time directly ex...
Abstract NTN1 is expressed in a wide range of developmental tissues and essential for normal development. Here we describe the generation Netrin-1 reporter chicken line ( NTN1-T2A-eGFP ) by targeting green fluorescent protein into locus using CRISPR/Cas9 methodology. Our strategy gave 100% transmission heterozygous T2A − eGFP /+ embryos which GFP localisation faithfully replicated endogenous expression optic fissure neural tube floorplate. Furthermore, all hatched birds appeared...
Signaling via the colony-stimulating factor 1 receptor (CSF1R) controls survival, differentiation, and proliferation of macrophages. Mutations in CSF1 or CSF1R mice rats have pleiotropic effects on postnatal somatic growth. We tested possible application pig CSF1-Fc fusion protein as a therapy for low birth weight (LBW) at term, using model based maternal dexamethasone treatment rats. Neonatal did not alter growth increase blood monocyte count. Instead, there was substantial size liver both...
Abstract Bovine alveolar macrophages (AMs) defend the lungs against pathogens such as Mycobacterium bovis ( M. bovis) , causative agent of bovine tuberculosis. However, little is known about surface molecules expressed by AMs and whether there heterogeneity within population. The purpose this study was to characterise AM cell phenotype using flow cytometry. Bronchoalveolar lavage samples from four different calves were stained with a combination antibodies immune prior cytometric analysis....
The siglecs (sialic acid-binding Ig-like lectins) are a family of transmembrane receptors expressed in the haemopoietic, immune and nervous systems. CD33-related distinct subset mostly innate system where they can function as inhibitory by suppressing signalling mediated coupled with ITAMs (immunoreceptor tyrosine-based activation motifs). contain ITIMs motifs) that recruit activate SHP-1 [SH2 (Src homology 2) domain-containing phosphatase-1] SHP-2. In addition, suppress siglec-dependent...
Abstract Expression of Csf1r in adults is restricted to cells the macrophage lineage. Transgenic reporters based upon locus require inclusion highly conserved Fms-intronic regulatory element for expression. We have created Csf1r-EGFP transgenic sheep via lentiviral transgenesis a construct containing elements mouse and promoter. Committed bone marrow precursors blood monocytes express EGFP these animals. Sheep were divided into three populations, similar classical, intermediate, nonclassical...
Abstract The genomes of RNA and small DNA viruses vertebrates display significant suppression CpG dinucleotide frequencies. Artificially increasing frequencies results in substantial attenuation virus replication, suggesting that these compositional changes may facilitate recognition non-self sequences. Recently, the interferon inducible protein ZAP, was identified as host factor responsible for sensing viral RNA, through direct binding possibly downstream targeting degradation. Using an...
Abstract Airway inflammation is highly prevalent in horses, with the majority of non-infectious cases being defined as equine asthma. Currently, cytological analysis airway derived samples principal method assessing lower inflammation. Samples can be obtained by tracheal wash (TW) or lavage respiratory tract (bronchoalveolar (BAL) fluid; BALF). Although BALF cytology carries significant diagnostic advantages over TW for diagnosis asthma, sample acquisition invasive, making it prohibitive...
Transforming growth factor β1 (TGF-β1) is a known regulator of chondrocyte proliferation and promotes cartilage repair in osteoarthritis (OA). microRNA-29b-3p (miR-29b-3p) downregulated by TGF-β1 overexpressed OA cartilage. However, the ability miR-29b-3p to mediate pro-proliferative effects not yet understood. This current study aimed investigate effect on TGF-β1-induced cell murine articular chondrocytes. The stimulation chondrocytes for 24 h resulted downregulation expression. ratio G0/G1...
Summary The methylotrophic yeast Pichia pastoris is commonly used for the production of recombinant proteins at scale. identification an optimally overexpressing strain following transformation can be time and reagent consuming. Fluorescent reporters like GFP have been to assist superior producers, but their relatively big size, maturation requirements narrow temperature range restrict applications. Here, we introduce use iLOV, a flavin‐based fluorescent protein, as marker identify P....
In the precision medicine era, genetic diagnoses direct clinical management and lead to improved health outcomes. However, there is scant data on role of race or social determinants (SDH) in access medical genetics evaluation outcomes testing general adult population. This study examines whether race, ethnicity, measures SDH influence results
NTN1 is expressed in a wide range of developmental tissues and essential for normal development. Here we describe the generation Netrin-1 reporter chicken line (NTN1-T2A-eGFP) by targeting green fluorescent protein into locus using CRISPR/Cas9 methodology. Our strategy gave 100% transmission heterozygous (NTN1T2A-eGFP/+) embryos which GFP localisation faithfully replicated endogenous expression optic fissure neural tube floorplate. Furthermore, all NTN1T2A-eGFP/+ hatched birds appeared...
It is estimated that animals pollinate 87.5% of flowering plants worldwide and managed honey bees (Apis mellifera) account for 30-50% this ecosystem service to agriculture. In addition their important role as pollinators, are well-established insect models studying learning memory, behavior, caste differentiation, epigenetic mechanisms, olfactory biology, sex determination, eusociality. Despite importance agriculture, knowledge bee biology lags behind many other livestock species. study, we...
Abstract Loss of function variants in the NF1 gene cause neurofibromatosis type 1 (NF1), a genetic disorder characterized by complete penetrance, prevalence 3,000, characteristic physical exam findings, and substantially increased risk for malignancy. However, our understanding is entirely based on patients ascertained through phenotype-first approaches. Leveraging genotype-first approach two large patient cohorts, we demonstrate unexpectedly high (1 450-750) pathogenic variants. Half were...
Abstract Macrophages activated with interferons (IFNs) respond transcriptional changes that enhance clearance of intracellular pathogens such as Toxoplasma , a ubiquitous apicomplexan parasite infects more than billion people worldwide. Although IFNs generally inhibit the can also induce components host IFN signalling pathway to survival in cells. Compared type II gamma (IFNγ), role I macrophage response is relatively not well characterized. Here, using fluorescent and CRISPR/Cas9 knockout...