A5044664283- Streptococcal Infections and Treatments
- Antimicrobial Resistance in Staphylococcus
- Blood Coagulation and Thrombosis Mechanisms
- Neonatal and Maternal Infections
- Trauma, Hemostasis, Coagulopathy, Resuscitation
- Sepsis Diagnosis and Treatment
- Protease and Inhibitor Mechanisms
- Neuroscience and Neuropharmacology Research
- Urinary Bladder and Prostate Research
- Pelvic floor disorders treatments
- Pulmonary Hypertension Research and Treatments
- Bacterial Identification and Susceptibility Testing
- Blood properties and coagulation
- Urinary Tract Infections Management
- Traumatic Brain Injury and Neurovascular Disturbances
- Advanced MRI Techniques and Applications
- Medical Imaging Techniques and Applications
- Vitamin K Research Studies
- Cardiovascular Function and Risk Factors
- Ion channel regulation and function
- Infective Endocarditis Diagnosis and Management
- Neuroinflammation and Neurodegeneration Mechanisms
- Platelet Disorders and Treatments
- Antimicrobial Peptides and Activities
- Stoma care and complications
University of Notre Dame
2015-2024
Transgene (France)
2010-2023
National Institute of Neurological Disorders and Stroke
2012
National Institutes of Health
2012
University of Southern California
2012
W. M. Keck Foundation
2010
Mount Sinai Hospital
2010
Coagulopathy in traumatic brain injury (CTBI) is a well-established phenomenon, but its mechanism poorly understood. Various studies implicate protein C activation related to the global insult of hemorrhagic shock or tissue factor release with resultant platelet dysfunction and depletion coagulation factors. We hypothesized that CTBI distinct phenomenon from coagulopathy following shock.We used thrombelastography mapping as measure function, assessing degree inhibition adenosine diphosphate...
The protein C (PC) pathway is a well-characterized coagulation system. Endothelial PC receptors and thrombomodulin mediate the conversion of to its activated form, potent anticoagulant anti-inflammatory molecule. Here we show that expressed on intestinal epithelial cells. expression endothelial receptor down-regulated In patients with inflammatory bowel disease. −/− /PC(Tg) mice, expressing only 3% WT PC, developed spontaneous inflammation were prone severe experimental colitis. These mice...
Acute lung injury (ALI) and systemic coagulopathy are serious complications of traumatic brain (TBI) that frequently lead to poor clinical outcomes. Although the release tissue factor (TF), a potent initiator extrinsic pathway coagulation, from injured is thought play key role in after TBI, its function ALI following TBI remains unclear. In this study, we investigated whether appearance TF correlated with ensuing follows using an anesthetized rat blunt trauma model. Blood samples were...
Modularly assembled, antimicrobial peptide capped phage-mimicking nanoparticles are highly biocompatible, rapidly bactericidal, and clear wound infections without the emergence of antibacterial resistance.
Acute coagulopathy is a serious complication of traumatic brain injury (TBI) and uncertain etiology because the complex nature TBI. However, recent work has shown correlation between mortality abnormal hemostasis resulting from early platelet dysfunction. The aim current study was to develop characterize rodent model TBI that mimics human coagulopathic condition so mechanisms acute in can be more readily assessed. Studies utilizing highly reproducible constrained blunt-force rats demonstrate...
Plasminogen activator inhibitor-1 (PAI-1) is known to protect mice against cardiac fibrosis. It has been speculated that PAI-1 may regulate fibrosis by inactivating urokinase-type plasminogen (uPA) and ultimately plasmin (Pm) generation. However, the in vivo role of uPA limiting generation Pm during remains be established. The objective this study was determine if cardioprotective effect mediated through its ability directly urokinase -mediated activation (Pg). An Angiotensin II...
A number of studies have identified a role for plasminogen activator inhibitor-1 (PAI-1) in regulating angiogenesis, although results from these investigations been controversial. Among key cellular components an angiogenic vessel are endothelial cells (ECs), which known to express several the fibrinolytic system, including PAI-1. Thus, alterations expression this protein may direct effects on cell functions involved vascular development. In study, ECs were isolated sections murine arterial...
The cluster of virulence sensor (CovS)/responder (CovR) two-component operon (CovRS) regulates ∼15% the genes Group A Streptococcal pyogenes (GAS) genome. Bacterial clones containing inactivating mutations in covS gene have been isolated from patients with virulent invasive diseases. We report herein an assessment nature and types that can occur both nonvirulent GAS strains, assess whether a attain enhanced through this mechanism. group mice were infected globally-disseminated clonal M1T1...
Coagulopathy after severe traumatic brain injury (TBI) has been extensively reported. Clinical studies have identified a strong relationship between diminished platelet-rich thrombus formation, responsiveness to adenosine diphosphate agonism, and severity of TBI. The mechanisms that lead platelet dysfunction in the acute response TBI are poorly understood. development rodent model mimics coagulopathy observed clinically recently Using immunohistochemical techniques thromboelastography...
The genome of an invasive skin-tropic strain (AP53) serotype M53 group A Streptococcus pyogenes (GAS) is composed a circular chromosome 1,860,554 bp and carries genetic markers for infection at skin locales, viz, emm gene family pattern D FCT type 3. Through genome-scale comparisons AP53 with other GAS genomes, we identified 596 candidate single-nucleotide polymorphisms (SNPs) that reveal potential basis tropism. differed by ∼30 point mutations from noninvasive (Alab49), 4 which are located...
Abstract Catheter-associated urinary tract infections (CAUTIs) are amongst the most common nosocomial worldwide and difficult to treat partly due development of multidrug-resistance from CAUTI-related pathogens. Importantly, CAUTI often leads secondary bloodstream death. A major challenge is predict when patients will develop CAUTIs which populations at-risk for infections. Catheter-induced inflammation promotes fibrinogen (Fg) fibrin accumulation in bladder exploited as a biofilm formation...
Streptokinase (SK), secreted by Group A Streptococcus (GAS), is a single-chain ∼47-kDa protein containing three consecutive primary sequence regions that comprise its α, β, and γ modules. Phylogenetic analyses of the variable β-domain sequences from different GAS strains suggest SKs can be arranged into two clusters, SK1 SK2, with subdivision SK2 SK2a SK2b. SK2b skin-tropic Pattern D M-protein also express plasminogen (human Pg (hPg)) binding streptococcal (PAM) as major cell surface...
Sepsis-induced acute kidney injury (AKI) contributes to the high mortality and morbidity in patients. Although pathogenesis of AKI during sepsis is poorly understood, it well accepted that plasminogen activator inhibitor-1 (PAI-1) vitronectin (Vn) are involved AKI. However, functional cooperation between PAI-1 Vn septic has not been completely elucidated. To address this issue, mice were utilized lacking either (PAI-1−/−) or expressing a PAI-1-mutant (PAI-1R101A/Q123K) which interaction...
The bacterial pathogen Group A Streptococcus (GAS) has been shown to induce a variety of human diseases ranging in severity from pharyngitis toxic shock syndrome and necrotizing fasciitis. One the major virulence factors produced by GAS is peptide toxin Streptolysin S (SLS). Though this long recognized as potent cytolysin, recent evidence our lab indicated that SLS-dependent cytotoxicity keratinocytes mediated through inactivation cytoprotective factor Akt1 subsequent activation...
The neuroprotective activity of conantokin-G (con-G), a naturally occurring antagonist N-methyl-D-aspartate receptors (NMDAR), was neurologically and histologically compared in the core peri-infarct regions after ischemia/reperfusion brain injury male Sprague-Dawley rats. contralateral served as robust internal controls. Intrathecal injection con-G, post-middle carotid artery occlusion (MCAO), caused dramatic decrease infarct size swelling at 4 hr, to 26 significant recovery neurological...
ABSTRACT Streptococcus pyogenes , or group A (GAS), is both a pathogen and an asymptomatic colonizer of human hosts produces large number surface-expressed secreted factors that contribute to variety infection outcomes. The GAS-secreted cysteine protease SpeB has been well studied for its effects on the host; however, despite broad proteolytic activity, studies how this factor utilized in polymicrobial environments are lacking. Here, we various forms evaluate antimicrobial antibiofilm...
Epigenetic regulation of vascular remodeling in pulmonary hypertension (PH) is poorly understood. Transcription regulating, histone acetylation code alters chromatin accessibility to promote transcriptional activation. Our goal was identify upstream mechanisms that disrupt epigenetic equilibrium PH.
Recruitment of the serine protease plasmin is central to pathogenesis many bacterial species, including Group A streptococcus (GAS), a leading cause morbidity and mortality globally. key process in invasive GAS disease ability accumulate at cell surface, however role host activators plasminogen this poorly understood. Here, we demonstrate for first time that urokinase-type activator (uPA) contributes recruitment subsequent initiation vivo. In absence source activators, streptokinase (Ska)...
Group A Streptococcus (GAS, pyogenes ) is a Gram-positive human pathogen that employs several secreted and surface-bound virulence factors to manipulate its environment, allowing it cause variety of disease outcomes. One such factor Streptolysin S (SLS), ribosomally-produced peptide toxin undergoes extensive post-translational modifications. The activity SLS has been studied for over 100 years owing rapid potent ability lyse red blood cells, the shown play major role in GAS vivo . We have...
Stroke is the third leading cause of death among Americans 65 years age or older1. The quality life for patients who suffer from a stroke fails to return normal in large majority patients2, which mainly due current lack clinical treatment acute stroke. This necessitates understanding physiological effects cerebral ischemia on brain tissue over time and major area active research. Towards this end, experimental progress has been made using rats as preclinical model stroke, particularly,...