- Blood Coagulation and Thrombosis Mechanisms
- COVID-19 Clinical Research Studies
- Long-Term Effects of COVID-19
- Cell Adhesion Molecules Research
- Protease and Inhibitor Mechanisms
- Platelet Disorders and Treatments
- Coagulation, Bradykinin, Polyphosphates, and Angioedema
- SARS-CoV-2 and COVID-19 Research
- Atherosclerosis and Cardiovascular Diseases
- Gut microbiota and health
- Blood properties and coagulation
- Venous Thromboembolism Diagnosis and Management
- Hemophilia Treatment and Research
- Zebrafish Biomedical Research Applications
- Liver Disease Diagnosis and Treatment
- RNA Interference and Gene Delivery
- Diet and metabolism studies
- Coronary Interventions and Diagnostics
- Nitric Oxide and Endothelin Effects
- Natural Antidiabetic Agents Studies
- Eicosanoids and Hypertension Pharmacology
- Advanced biosensing and bioanalysis techniques
- Retinal and Optic Conditions
- Atrial Fibrillation Management and Outcomes
- Myeloproliferative Neoplasms: Diagnosis and Treatment
MCPHS University
2023-2025
Boston University
2021-2025
University Medical Center of the Johannes Gutenberg University Mainz
2016-2023
Johannes Gutenberg University Mainz
2016-2023
Blood Systems Research Institute
2022
Versiti Blood Center of Wisconsin
2018-2021
University of North Carolina at Chapel Hill
2016-2019
Justus-Liebig-Universität Gießen
2014
PSG Institute of Medical Sciences & Research
2010
Meharry Medical College
1999
Animal models recapitulating COVID-19 are critical to enhance our understanding of SARS-CoV-2 pathogenesis. Intranasally inoculated transgenic mice expressing human angiotensin-converting enzyme 2 under the cytokeratin 18 promoter (K18-hACE2) represent a lethal model infection. We evaluated clinical and virological dynamics using two intranasal doses (104 106 PFUs), with detailed spatiotemporal pathologic analysis dose cohort. Despite generally mild-to-moderate pneumonia, decline resulting...
Rationale: Immune cells play an important role during the generation and resolution of thrombosis. T are powerful regulators immune nonimmune cell function, however, their in sterile inflammation venous thrombosis has not been systematically examined. Objective: This study investigated recruitment, activation, inflammatory activity deep vein its consequences for thrombus resolution. Methods Results: CD4 + CD8 infiltrate wall rapidly on induction remain tissue throughout In wall, recruited...
Atherosclerotic plaque development depends on chronic inflammation of the arterial wall. A dysbiotic gut microbiota can cause low-grade inflammation, and composition was linked to cardiovascular disease risk. However, role this environmental factor in atherothrombosis remains undefined. To analyze impact atherothrombosis, we rederived low-density lipoprotein receptor-deficient (Ldlr-/- ) mice as germfree (GF) kept these for 16 weeks an atherogenic high-fat Western diet (HFD) under GF...
Diet‐related health issues such as nonalcoholic fatty liver disease and cardiovascular disorders are known to have a major inflammatory component. However, the exact pathways linking diet‐induced changes (e.g., hyperlipidemia) ensuing inflammation remained elusive so far. We identified biological processes related innate immunity oxidative stress prime response in livers of low‐density lipoprotein receptor‐deficient mice on Western‐type diet using RNA sequencing silico functional analyses...
Key Points Hematopoietic cell–targeted antibody-drug conjugate preconditioning is highly effective for platelet gene therapy in hemophilia A mice. Platelet-specific FVIII can effectively prevent a needle-induced knee joint injury
Externalized histones erupt from the nucleus as extracellular traps, are associated with several acute and chronic lung disorders, but their implications in molecular pathogenesis of interstitial disease incompletely defined. To investigate role mechanisms externalized within immunologic networks pulmonary fibrosis, we studied human animal bronchoalveolar lavage (BAL) samples fibrosis. Neutralizing anti-histone antibodies were administered bleomycin-induced fibrosis C57BL/6 J mice,...
Atherosclerosis which results from gradual deposition of lipids in medium and large arteries is a leading cause mortality worldwide. Terminalia arjuna herb Combretaceae family contains hypolipidemic compounds flavonoids with high antioxidative properties. This study was conducted to determine the effect ethanolic fraction T. on blood atherosclerosis rabbits fed fat diet (HFD). Twenty New Zealand either sex were randomly divided into five groups: first two normal group HFD (21% fat) remaining...
SARS-CoV-2 infection disturbs the coagulation balance in blood, triggering thrombosis and contributing to organ failure. The role of prothrombotic metabolites COVID-19-associated coagulopathy remains elusive. Leveraging K18-hACE2 mice infected with SARS-CoV-2, we observed higher levels tryptophan metabolite, kynurenine, compared controls. SARS CoV-2 showed a significant upregulation enzymes controlling Kynurenine biogenesis, such as indoleamine 2,3-dioxygenase (IDO-1) kidneys liver,...
IntroductionCoronavirus disease 2019 (COVID-19), caused by SARS-CoV-2, is a public health emergency with phenotypes ranging from asymptomatic to severe sequelae that can lead multiple organ failure and death (1, 2). SARS-CoV-2 efficiently infects airway epithelial cells alveolar pneumocytes, causing in high viral loads inflammatory responses, including the interferon response (3). In hospitalized patients, COVID-19 increases risk of venous arterial thromboembolic events due vascular barrier...
Factor VII (FVII) activating protease (FSAP) is a circulating with putative function in blood coagulation and fibrinolysis. Genetic epidemiological studies have implied role for FSAP carotid stenosis, stroke thrombosis. To date, no vivo evidence available to support these claims. We have, the first time, used FSAP-/- mice define its thrombosis haemostasis characterise molecular mechanisms involved. FeCl3-induced arterial mesenteric artery revealed that occlusion time was significantly...
Activation of blood coagulation and endothelial inflammation are hallmarks respiratory infections with RNA viruses that contribute significantly to the morbidity mortality patients severe disease. We investigated how signaling by proteases affects quality extent response TLR3-ligand poly(I:C) in human cells. Genome-wide profiling documented additive synergistic effects thrombin on expression level many genes. The most active genes exhibiting induction costimulation included key mediators 2...
Animal models recapitulating distinctive features of severe COVID-19 are critical to enhance our understanding SARS-CoV-2 pathogenesis. Transgenic mice expressing human angiotensin-converting enzyme 2 (hACE2) under the cytokeratin 18 promoter (K18-hACE2) represent a lethal model infection. The precise mechanisms lethality in this mouse remain unclear. Here, we evaluated spatiotemporal dynamics infection for up 14 days post-infection. Despite and moderate pneumonia, rapid clinical decline or...
Identifying drug targets mitigating vascular dysfunction, thrombo‐inflammation and thromboembolic complications in COVID‐19 is essential. coagulopathy differs from sepsis coagulopathy. Factors that drive severe lung pathology coagulation abnormalities are not understood. Protein–protein interaction studies indicate the tagged viral bait protein ORF9c directly interacts with PAR2, which modulates host cell IFN inflammatory cytokines. In addition to direct of SARS‐CoV‐2 PARs, we speculate...
Abstract Influenza A virus infection is a common respiratory tract infection. Alveolar hemorrhage has been reported in patients with influenza pneumonia and mice infected A. In this study, we investigated the effect of two anticoagulants on alveolar after ( IAV ) wild‐type mice. Wild‐type were anticoagulated either warfarin or direct thrombin inhibitor dabigatran etexilate then mouse‐adapted (A/Puerto Rico/8/34 H1N1). was assessed by measuring hemoglobin levels bronchoalveolar lavage fluid...
Advanced age is associated with an increased susceptibility to Coronavirus Disease (COVID)-19 and more severe outcomes, although the underlying mechanisms are understudied. The lung endothelium located next infected epithelial cells bystander inflammation may contribute thromboinflammation COVID-19-associated coagulopathy. Here, we investigated age-associated SARS-CoV-2 pathogenesis endothelial inflammatory responses using humanized K18-hACE2 mice. Survival was reduced 20% in aged mice...
: The gut microbial metabolite, trimethylamine N-oxide (TMAO), was previously reported to induce platelet hypersensitivity, which leads thrombotic risk. However, the molecular mechanism underlying effects of TMAO on endothelial cells (EC), is primary vessel wall contact with lumen, remains unclear. Here, we investigated impact procoagulant activity (PCA) in EC and mice, for a possible link between microbiota coagulation. To test PCA EC, performed one-stage clotting assays converted into PCA....
Citation: Subramaniam S, Mohiuddin N and Jose A (2024) Does SARS-CoV-2 infect platelets? Front. Immunol. 15:1392000. doi: 10.3389/fimmu.2024.1392000