- Platelet Disorders and Treatments
- Blood Coagulation and Thrombosis Mechanisms
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Blood properties and coagulation
- COVID-19 Clinical Research Studies
- Advanced Chemical Physics Studies
- Cell Adhesion Molecules Research
- Antiplatelet Therapy and Cardiovascular Diseases
- Acute Ischemic Stroke Management
- Surface and Thin Film Phenomena
- Cancer-related molecular mechanisms research
- Protease and Inhibitor Mechanisms
- Neuroinflammation and Neurodegeneration Mechanisms
- Catalytic Processes in Materials Science
- Extracellular vesicles in disease
- Immune Response and Inflammation
- Polyamine Metabolism and Applications
- Immune Cell Function and Interaction
- Inflammatory Biomarkers in Disease Prognosis
- Nitric Oxide and Endothelin Effects
- Venous Thromboembolism Diagnosis and Management
- Hemophilia Treatment and Research
- Metabolism and Genetic Disorders
- Electron and X-Ray Spectroscopy Techniques
- Long-Term Effects of COVID-19
University of Utah
2016-2025
Washington University in St. Louis
2024-2025
University of North Carolina at Chapel Hill
2005-2024
Queensland Children’s Hospital
2024
University of North Carolina Hospitals
2023
General Department of Preventive Medicine
2020-2021
GTx (United States)
2021
Center for Neurosciences
2021
Geriatric Research Education and Clinical Center
2020
Universität Greifswald
2018
Estrogen receptors (ERs) mediate most of the biological effects estrogen in mammary and uterine epithelial cells by binding to response elements promoter region target genes or through protein-protein interactions. Anti-estrogens such as tamoxifen inhibit growth ER-positive breast cancers reducing expression estrogen-regulated genes. However, anti-estrogen-resistant tumors remains a significant clinical problem. Here we show that phosphatidylinositol (PI) 3-kinase AKT activate ERalpha...
Human β-defensins (hBD) are antimicrobial peptides that curb microbial activity. Although hBD's primarily expressed by epithelial cells, we show human platelets express hBD-1 has both predicted and novel antibacterial activities. We observed activated surround Staphylococcus aureus (S. aureus), forcing the pathogens into clusters have a reduced growth rate compared to S. alone. Given microbicidal activity of β-defensins, determined whether hBD family members were present in found mRNA...
Ischemic stroke prompts a strong inflammatory response, which is associated with exacerbated outcomes. In this study, we investigated mechanistic regulators of neutrophil extracellular trap (NET) formation in and whether they contribute to NET-forming neutrophils were found throughout brain tissue ischemic patients, elevated plasma NET biomarkers correlated worse Additionally, observed increased platelet surface-expressed high-mobility group box 1 (HMGB1) patients. Mechanistically, platelets...
Platelets are crucial players in hemostasis and thrombosis, but also contribute to immune regulation host defense, using different receptors, signaling pathways effector functions, respectively. Whether distinct subsets of platelets specialize these diverse tasks is insufficiently understood. Here, we employed an vivo pulse-labelling method Mus musculus models for tracking platelet ageing its functional implications. Using vitro assays, reveal that young, reticulated show heightened...
Abstract: The analgesic effect of preoperatively administered ibuprofen was evaluated in 107 dental outpatients undergoing the removal impacted third molars. Subjects were given 800 mg prior to procedure and 400 4 8 hours later. Comparison made groups receiving either placebo at all three doses, 600 acetaminophen on same schedule, or followed by two doses postoperatively plus 60 codeine. Ibuprofen pretreatment resulted significantly less pain than as local anesthetic wore off. also...
Poly(amidoamine) (PAMAM) dendrimers are increasingly studied as model nanoparticles for a variety of biomedical applications, notably in systemic administrations. However, with respect to blood-contacting amine-terminated have recently been shown activate platelets and cause fatal, disseminated intravascular coagulation (DIC)-like condition mice rats. We here demonstrate that, upon addition blood, cationic G7 PAMAM induce fibrinogen aggregation, which may contribute the vivo DIC-like...
Fetal mouse liver and normal human bone marrow cell cultures were used for studies on the inhibition of erythroid colony formation (CFU-E) by sera from anemic patients with end-stage renal failure polyamine spermine. Sera each eight predialysis uremic produced a significant (P < 0.001) in fetal when compared to volunteers. In vivo or vitro dialysis 3,500-dalton exclusion limit membrane removed inhibitor sera. The serum dialysate provided fractionation was significantly inhibitory cultures....
Poly(amidoamine) (PAMAM) dendrimers have been proposed for a variety of biomedical applications and are increasingly studied as model nanomaterials such use. The dendritic structure features both modular synthetic control molecular size shape presentation multiple equivalent terminal groups. These properties make PAMAM highly functionalizable, versatile single-molecule nanoparticles with high degree consistency low polydispersity. Recent nanotoxicological studies showed that intravenous...
Neutrophil granulocytes, also called polymorphonuclear leukocytes (PMNs), extrude molecular lattices of decondensed chromatin studded with histones, granule enzymes, and antimicrobial peptides that are referred to as neutrophil extracellular traps (NETs). NETs capture contain bacteria, viruses, other pathogens. Nevertheless, experimental evidence indicates cause inflammatory vascular tissue damage, suggesting identifying pathways inhibit NET formation may have therapeutic implications. Here,...
The small GTPase RAP1 is critical for platelet activation and thrombus formation. activity in platelets controlled by the GEF CalDAG-GEFI an unknown regulator that operates downstream of adenosine diphosphate (ADP) receptor, P2Y12, a target antithrombotic therapy. Here, we provide evidence GAP, RASA3, inhibits provides link between P2Y12 signaling pathway. In mice, reduced expression RASA3 led to premature markedly life span circulating platelets. increased turnover resulting...
Coronavirus disease 2019 (COVID-19) is associated with derangement in biomarkers of coagulation and endothelial function has been likened to the coagulopathy sepsis. However, clinical laboratory metrics suggest key differences these pathologies. We sought determine whether plasma fibrinolytic potential patients COVID-19 differ compared healthy donors critically ill Approach Results: performed comparative studies on plasmas from a single-center, cross-sectional observational study 99...
Abstract COVID-19 rapidly emerged as a crippling public health crisis in the last few months, which has presented series risk. Understanding of immune response and biomarker analysis is needed to progress toward understanding disease pathology developing improved treatment options. The goal this study identify pathogenic factors that are linked severity patient characteristics. Patients with who were hospitalized from March 17 June 5, 2020 analyzed for clinical features soluble plasma...
Age-related microvascular dysfunction is well characterized in rodents and humans, but little known about the properties of endothelial glycocalyx advanced age. We examined microvessels young old male C57BL6 mice (young: 6.1 ± 0.1 mo vs. old: 24.6 0.2 mo) using intravital microscopy transmission electron human participants 29 1 yr 60 2 yr) microscopy. Glycocalyx thickness mesenteric skeletal muscle was 51-54% lower compared with mice. also observed 33% sublingual microcirculation humans The...