A5033359012- Blood Coagulation and Thrombosis Mechanisms
- Platelet Disorders and Treatments
- Coagulation, Bradykinin, Polyphosphates, and Angioedema
- Protease and Inhibitor Mechanisms
- Antiplatelet Therapy and Cardiovascular Diseases
- Cell Adhesion Molecules Research
- Receptor Mechanisms and Signaling
- Cancer-related gene regulation
- Wnt/β-catenin signaling in development and cancer
- Venous Thromboembolism Diagnosis and Management
- Biochemical and Structural Characterization
- Renal Diseases and Glomerulopathies
- Complement system in diseases
- Kruppel-like factors research
- Atrial Fibrillation Management and Outcomes
- Renin-Angiotensin System Studies
- Extracellular vesicles in disease
- Chronic Kidney Disease and Diabetes
- MicroRNA in disease regulation
- Neuropeptides and Animal Physiology
- Computational Drug Discovery Methods
- Hemophilia Treatment and Research
- Trauma, Hemostasis, Coagulopathy, Resuscitation
- Cardiac electrophysiology and arrhythmias
- Inflammatory Biomarkers in Disease Prognosis
Case Western Reserve University
2016-2025
University School
2008-2025
Catholic Medical Center
2024
Mercy Catholic Medical Center
2024
Vanderbilt University Medical Center
2023
Thomas Jefferson University
2022
Harvard University
2017
Georgia Institute of Technology
2013
Emory University
2013
Case Comprehensive Cancer Center
2009
E-cadherin is a transmembrane glycoprotein that mediates calcium-dependent, homotypic cell–cell adhesion and plays role in maintaining the normal phenotype of epithelial cells. Decreased expression has been correlated with increased invasiveness breast cancer. In other systems, inappropriate nonepithelial cadherin, such as N-cadherin, by an cell shown to downregulate contribute scattered phenotype. this study, we explored possibility cadherins may be motility invasion cancer We show...
Coagulation factor XII (FXII) deficiency is associated with decreased neutrophil migration, but the mechanisms remain uncharacterized. Here, we examine how FXII contributes to inflammatory response. In 2 models of sterile inflammation, FXII-deficient mice (F12-/-) had fewer neutrophils recruited than WT mice. We discovered that produced a pool functionally distinct from hepatic-derived and trafficking at sites inflammation. signals in through urokinase plasminogen activator receptor-mediated...
Abstract Serotonin receptors (5-HT 3A R) directly regulate gut movement, and drugs that inhibit 5-HT R function are used to control emetic reflexes associated with gastrointestinal pathologies cancer therapies. The involves a finely tuned orchestration of three domain movements include the ligand-binding domain, pore intracellular domain. Here, we present structure from full-length channel in apo-state determined by single-particle cryo-electron microscopy at nominal resolution 4.3 Å. In...
Treatment of bleeding disorders using transfusion donor-derived platelets faces logistical challenges due to their limited availability, high risk contamination, and short (5 7 days) shelf life. These could be potentially addressed by designing platelet mimetics that emulate the adhesion, aggregation, procoagulant functions platelets. To this end, we created liposome-based platelet-mimicking nanoparticles (PPNs) can expose phospholipid phosphatidylserine on surface in response plasmin....
Thrombin is a potent platelet agonist that activates platelets and other cells of the cardiovascular system by cleaving its G-protein-coupled receptors, protease-activated receptor 1 (PAR1), PAR4, or both. We now show PAR1 PAR4 with α-thrombin induces heterodimer formation. PAR1-PAR4 heterodimers were not detected when unstimulated; however, stimulated 10 nm α-thrombin, we able to detect strong interaction between bioluminescence resonance energy transfer. In contrast, activating receptors...
Significance The human circulatory system includes the heart, arteries, veins, and capillaries, all of which are lined by endothelial cells to prevent escape vascular contents into surrounding tissues. Platelets blood that best known for their essential role in preventing loss after injury. Here, we employed sensitive methods measure changes barrier function vivo used them identify a platelets maintaining homeostasis. results highlight platelet collagen receptors dense granules, show vessels...
The cell–cell adhesion molecule N-cadherin, with its associated catenins, is expressed by differentiating skeletal muscle and precursors. Although N-cadherin's role in later events of myogenesis such as during myoblast fusion well established, less known about earlier commitment differentiation. Using an vitro model system, we have determined that N-cadherin– mediated enhances differentiation three-dimensional cell aggregates. We transfected the cadherin-negative BHK fibroblastlike line...
Arterial thrombosis (blood clot) is a common complication of many systemic diseases associated with chronic inflammation, including atherosclerosis, diabetes, obesity, cancer and autoimmune rheumatologic disorders. Thrombi are the cause most heart attacks, strokes extremity loss, making an extremely important public health problem. Since these thrombi stem from inappropriate platelet activation subsequent coagulation, targeting systems therapeutically has clinical significance for developing...
Severe hemorrhage associated with trauma, surgery, and congenital or drug-induced coagulopathies can be life-threatening requires rapid hemostatic management via topical, intracavitary, intravenous routes. For injuries that are not easily accessible externally, approaches needed. The clinical gold standard for this is transfusion of blood products, but due to donor dependence, specialized storage requirements, high risk contamination, short shelf life, product use faces significant...
Background Chronic kidney disease (CKD) is a leading cause of death, its progression driven by glomerular podocyte injury and loss, manifesting as proteinuria. Proteinuria includes loss coagulation zymogens, cofactors, inhibitors resulting in hypercoagulable state characterized enhanced thrombin generation. Both CKD proteinuria significantly increase the risk thromboembolic disease. Meanwhile, anticoagulant medications (which antagonize thereby prevent thromboembolism) have been shown to...
ABSTRACT The cadherin/catenin complex mediates Ca2+-dependent cell-cell interactions that are essential for normal developmental processes. It has been proposed sorting of cells during embryonic development is due, at least in part, to expression different cadherin family members or differing levels a single member. Expression dominant-negative cadherins used experimentally decrease whole organisms and cultured cells. In this study, we elucidated the mechanism action extracellular...
Protease activated receptor (PAR) 4 (gene: F2RL3) harbors a functional dimorphism, rs773902 A/G (encoding Thr120/Ala120, respectively) and is associated with greater platelet aggregation. The A allele frequency more common in Black individuals, individuals have higher incidence of ischemic stroke than White individuals. However, it not recognized whether the responsible for worse outcomes. To directly test vivo effect this variant on stroke, we generated mice where F2rl3 was replaced by...
Investigations determined the critical amino acids for α-thrombin's interaction with protease-activated receptors 1 and 4 (PAR1 PAR4, respectively) at thrombin cleavage site. Recombinant PAR1 wild-type (wt) exodomain was cleaved by α-thrombin a Km of 28 μM, kcat 340 s-1, kcat/Km 1.2 × 107. When P4 or P2 position mutated to alanine, PAR1-L38A PAR1-P40A, respectively, unchanged, 29 23 respectively; however, were reduced in each case. In contrast, when Asp39 P3 PAR1-D39A, both ∼3-fold, making...