A5101684704- Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis
- Neonatal Respiratory Health Research
- Pulmonary Hypertension Research and Treatments
- Immune Cell Function and Interaction
- T-cell and B-cell Immunology
- Immunotherapy and Immune Responses
- Asthma and respiratory diseases
- Medical Imaging and Pathology Studies
- RNA modifications and cancer
- Inhalation and Respiratory Drug Delivery
- Chronic Obstructive Pulmonary Disease (COPD) Research
- MicroRNA in disease regulation
- HIV Research and Treatment
- Tissue Engineering and Regenerative Medicine
- Immune Response and Inflammation
- Extracellular vesicles in disease
- Occupational and environmental lung diseases
- Influenza Virus Research Studies
- Tracheal and airway disorders
- Respiratory viral infections research
- Cancer-related molecular mechanisms research
- Eosinophilic Disorders and Syndromes
- Chronic Myeloid Leukemia Treatments
- Mast cells and histamine
- PI3K/AKT/mTOR signaling in cancer
Boehringer Ingelheim (Germany)
2019-2025
University of Bath
2020-2024
Boehringer Ingelheim (Australia)
2024
University of Groningen
2022
State College of Florida Manatee-Sarasota
2021
University of Washington
2006-2020
AstraZeneca (Sweden)
2016-2018
California Polytechnic State University
2018
Novartis (United Kingdom)
2004-2017
Novartis (United States)
2015
Existing mouse models of lethal Ebola virus infection do not reproduce hallmark symptoms hemorrhagic fever, neither delayed blood coagulation and disseminated intravascular nor death from shock, thus restricting pathogenesis studies to nonhuman primates. Here we show that mice the Collaborative Cross panel recombinant inbred exhibit distinct disease phenotypes after mouse-adapted infection. Phenotypes range complete resistance severe fever characterized by prolonged times 100% mortality....
The pathogenesis of pulmonary arterial hypertension (PAH) remains unclear. 4 microRNAs representing the miR-143 and miR-145 stem loops are genomically clustered.To elucidate transcriptional regulation miR-143/145 cluster role in PAH.We identified promoter region that regulates microRNA expression artery smooth muscle cells (PASMCs). We mapped PAH-related signaling pathways, including estrogen receptor, liver X factor/retinoic transforming growth factor-β (Smads), hypoxia (hypoxia response...
Studies of the host response to virus infection typically focus on protein-coding genes. However, non-protein-coding RNAs (ncRNAs) are transcribed in mammalian cells, and roles many these ncRNAs remain enigmas. Using next-generation sequencing, we performed a whole-transcriptome analysis severe acute respiratory syndrome coronavirus (SARS-CoV) across four founder mouse strains Collaborative Cross. We observed differential expression approximately 500 annotated, long 1,000 nonannotated...
The complex pathologies associated with severe pulmonary arterial hypertension (PAH) in humans have been a challenge to reproduce mice due the subtle phenotype displayed PAH stimuli.Here we aim develop novel murine model of that recapitulates more pathologic processes, such as vascular remodeling and cardiac indices, are not characteristic alternative mouse models.Inhibition endothelial growth factor receptor (VEGFR) SU5416 combined 3 weeks chronic hypoxia was investigated. Hemodynamics,...
We studied the effect of filovirus infection on host cell gene expression by characterizing regulation responses in human liver cells infected with Zaire Ebolavirus (ZEBOV), Reston (REBOV), and Marburgvirus (MARV), using transcriptional profiling bioinformatics. Expression microarray analysis demonstrated that resulted up-regulation immune-related genes down-regulation many coagulation acute-phase proteins. These studies further revealed a common feature virulence is suppression key cellular...
Background— Pulmonary arterial hypertension (PAH) is a hyperproliferative vascular disorder observed predominantly in women. Estrogen potent mitogen human pulmonary artery smooth muscle cells and contributes to PAH vivo; however, the mechanisms attributed this causation remain obscure. Curiously, heightened expression of estrogen-metabolizing enzyme cytochrome P450 1B1 (CYP1B1) reported idiopathic murine models PAH. Methods Results— Here, we investigated putative pathogenic role CYP1B1...
The incidence of pulmonary arterial hypertension is greater in women, suggesting estrogens may play a role the disease pathogenesis. Experimentally, males, exogenously administered estrogen can protect against (PH). However, models that display female susceptibility, causative role.To clarify influence endogenous and sex PH assess therapeutic potential clinically available aromatase inhibitor.We interrogated effect reduced males females using inhibitor, anastrozole, two PH: hypoxic mouse...
Loss of the growth-suppressive effects bone morphogenetic protein (BMP) signaling has been demonstrated to promote pulmonary arterial endothelial cell dysfunction and induce smooth muscle (PASMC) proliferation, leading development hypertension (PAH). MicroRNAs (miRs) mediate higher order regulation cellular function through coordinated modulation mRNA targets; however, miR expression is altered by disease drug therapy. Here, we examined treatment-naive patients experimental models PAH...
The genome sequence of the ferret, a model human respiratory disease, enables research on influenza and cystic fibrosis. domestic ferret (Mustela putorius furo) is an important animal for multiple diseases. It considered 'gold standard' modeling virus infection transmission1,2,3,4. Here we describe 2.41 Gb draft assembly constituting 2.28 plus gaps. We annotated 19,910 protein-coding genes this using RNA-seq data from 21 tissues. characterized host response to two infections by analysis 42...
The outcome of respiratory virus infection is determined by a complex interplay viral and host factors. Some potentially important factors for the antiviral response, whose functions remain largely unexplored, are long non-coding RNAs (lncRNAs). Here we systematically inferred regulatory lncRNAs in response to influenza A severe acute syndrome coronavirus (SARS-CoV) based on their similarity expression with genes known function. We performed total RNA-Seq viral-infected lungs from eight...
Progressive accrual of senescent cells in aging and chronic diseases is associated with detrimental effects tissue homeostasis. We found that fibroblasts epithelia were not only refractory to macrophage-mediated engulfment removal, but they also paralyzed the ability macrophages remove bystander apoptotic corpses. Senescent cell-mediated efferocytosis suppression (SCES) was independent senescence-associated secretory phenotype (SASP) instead required direct contact between cells. SCES...
Despite advancements in antifibrotic therapy, idiopathic pulmonary fibrosis (IPF) remains a medical condition with unmet needs. Single-cell RNA sequencing (scRNA-seq) has enhanced our understanding of IPF but lacks the cellular tissue context and gene expression localization that spatial transcriptomics provides. To bridge this gap, we profiled control patient lung using transcriptomics, integrating data an scRNA-seq atlas. We identified three disease-associated niches unique compositions...
The sphingosine 1-phosphate (S1P) receptor agonist FTY720 is well known for its immunomodulatory activity, sequestering lymphocytes from blood and spleen into secondary lymphoid organs thereby preventing their migration to sites of inflammation. Because inflammation critically dependent on a balance between Ag-specific Th/effector cells T-regulatory cells, we investigated the effect cell trafficking functional activity. An increased number CD4+/CD25+ T was found in spleens FTY720-treated...
Recent outbreaks of avian influenza in humans have stressed the need for an improved nonhuman primate model pathogenesis. In order to further develop a macaque model, we expanded our previous vivo genomics experiments with virus-infected macaques by focusing on innate immune response at day 2 postinoculation and gene expression affected lung tissue viral genetic material present. Finally, sought identify signature genes early infection whole blood. For these purposes, infected six pigtailed...
ABSTRACT We previously reported widespread differential expression of long non-protein-coding RNAs (ncRNAs) in response to virus infection. Here, we expanded the study through small RNA transcriptome sequencing analysis host both severe acute respiratory syndrome coronavirus (SARS-CoV) and influenza infections across four founder mouse strains Collaborative Cross, a recombinant inbred resource for mapping complex traits. observed over 200 diverse classes during A majority identified...
Abstract Cigarette smoke (CS) is the leading risk factor to develop COPD. Therefore, pathologic effects of whole CS on differentiation primary small airway epithelial cells (SAEC) were investigated, using from three healthy donors and COPD patients, cultured under ALI (air-liquid interface) conditions. The analysis physiology demonstrated that impaired barrier formation reduced cilia beat activity. Although, COPD-derived cultures preserved some features known CS-induced similarly pronounced...
ABSTRACT We previously hypothesized that efficient translation of influenza virus mRNA requires the recruitment P58 IPK , cellular inhibitor PKR, an interferon-induced kinase targets eukaryotic initiation factor eIF2α. also inhibits PERK, eIF2α is localized in endoplasmic reticulum (ER) and induced during ER stress. The ability to interact with inhibit multiple kinases suggests it a critical regulator both viral translation. In this study, we sought definitively define role infection...
Statin use is associated with a variety of overtly related muscle symptoms including pain, myalgia, creatine kinase elevations without pain myolysis and myositis (rhabdomyolysis), potentially fatal side effect that led to the withdrawal cerivastatin in 2001. Unintended drug response phenotypes have an impact on patient compliance sometimes health assessment risk individual basis could enhance therapeutic benefit. We therefore investigated whether common single nucleotide polymorphisms were...
ABSTRACT We are still inadequately prepared for an influenza pandemic due to the lack of a vaccine effective subtypes which majority human population has no prior immunity and could be produced rapidly in sufficient quantities. There is therefore urgent need investigate novel vaccination approaches. Using combination genomic traditional tools, this study compares protective efficacy macaques intrarespiratory live virus by truncating NS1 A/Texas/36/91 (H1N1) with that conventional based on...
Rationale: Whether idiopathic, familial, or secondary to another disease, pulmonary arterial hypertension (PAH) is characterized by increased vascular tone, neointimal hyperplasia, medial hypertrophy, and adventitial fibrosis. Imatinib, a potent receptor tyrosine kinase inhibitor, reverses remodeling in animal models of PAH improves hemodynamics exercise capacity selected patients with PAH.Objectives: Here we use both imatinib knockout animals determine the relationship between...