A5017167604- Respiratory Support and Mechanisms
- Sepsis Diagnosis and Treatment
- Hemoglobin structure and function
- Acute Kidney Injury Research
- Receptor Mechanisms and Signaling
- MicroRNA in disease regulation
- Ion channel regulation and function
- Cancer-related molecular mechanisms research
- Pulmonary Hypertension Research and Treatments
- Protein Kinase Regulation and GTPase Signaling
- Thermal Regulation in Medicine
- Redox biology and oxidative stress
- Asthma and respiratory diseases
- Intensive Care Unit Cognitive Disorders
- Heme Oxygenase-1 and Carbon Monoxide
- Adenosine and Purinergic Signaling
- Vitamin K Research Studies
- Erythrocyte Function and Pathophysiology
- Neuroscience of respiration and sleep
- Coagulation, Bradykinin, Polyphosphates, and Angioedema
- Vitamin C and Antioxidants Research
- Chronic Obstructive Pulmonary Disease (COPD) Research
- Blood Coagulation and Thrombosis Mechanisms
- RNA Research and Splicing
- Immune Response and Inflammation
University of Illinois Chicago
2023-2025
Vanderbilt University Medical Center
2020-2022
Pulmonary and Allergy Associates
2019-2020
Saint Louis University
2014
Increased endothelial permeability is central to the pathogenesis of sepsis and leads organ dysfunction death but endogenous mechanisms that drive increased are not completely understood. We previously reported cell-free hemoglobin (CFH), elevated in 80% patients with sepsis, increases lung microvascular an ex vivo human model cultured cells. In this study, we augmented a murine polymicrobial circulating CFH test hypothesis by inducing apoptosis. Mice were treated intraperitoneal injection...
We have established a novel and evolutionarily-conserved function for chloride intracellular channel proteins (CLICs) in regulating Rho/Rac GTPases downstream of G protein-coupled receptors (GPCRs). Endothelial CLIC1 CLIC4 are rapidly transiently re-localized from the cytoplasm to plasma membrane response GPCR ligand sphingosine-1-phosphate (S1P), both CLICs required activate Rac1 S1P, but how they perform this remains unknown. Biochemical studies suggest that act as non-specific ion...
We have established a novel and evolutionarily-conserved function for chloride intracellular channel proteins (CLICs) in regulating Rho/Rac GTPases downstream of G protein-coupled receptors (GPCRs). Endothelial CLIC1 CLIC4 are rapidly transiently re-localized from the cytoplasm to plasma membrane response GPCR ligand sphingosine-1-phosphate (S1P), both CLICs required activate Rac1 S1P, but how they perform this remains unknown. Biochemical studies suggest that act as non-specific ion...
Several reports suggest that antisense oligonucleotides against miR-33 might reduce cardiovascular risk in patients by accelerating the reverse cholesterol transport pathway. However, conflicting exist about impact of anti-miR-33 therapy on levels very low-density lipoprotein-triglycerides (VLDL-TAG).We test hypothesis controls hepatic VLDL-TAG secretion.Using therapeutic silencing and adenoviral overexpression miR-33, we show limits secretion targeting N-ethylmaleimide-sensitive factor...
Acute respiratory distress syndrome (ARDS) is an inflammatory lung disorder that frequently complicates critical illness and commonly occurs in sepsis. Although numerous clinical environmental risk factors exist, not all patients with develop ARDS, raising the possibility of genetic underpinnings for ARDS susceptibility. We have previously reported circulating cell-free hemoglobin (CFH) elevated during sepsis, higher levels predict worse outcomes. Excess CFH rapidly scavenged by haptoglobin...
Endothelial CLICs (chloride intracellular channel proteins) CLIC1 and CLIC4 are required for the GPCRs (G-protein-coupled receptors) S1PR1 (sphingosine-1-phosphate receptor 1) S1PR3 to activate small GTPases Rac1 (Ras-related C3 botulinum toxin substrate RhoA (Ras homolog family member A). To determine whether function in additional endothelial GPCR pathways, we evaluated CLIC thrombin signaling via thrombin-regulated PAR1 (protease-activated downstream effector RhoA.
Vitamin C (ascorbate, ASC) is a critical antioxidant in the body with specific roles brain. Despite recent interest vitamin therapies for care medicine, little known about regulation during acute inflammation and illnesses such as sepsis. Using cecal slurry (CS) model of sepsis mice, we determined ASC inflammatory changes brain following initial treatment. levels were acutely decreased by approximately 10% at 4 24 h post CS Changes accompanied robust increase liver up to 50%, indicating...
Mouse models of acute lung injury (ALI) have been instrumental for studies the biological underpinnings inflammation and permeability, but murine sepsis generate minimal injury. Our goal was to create a model ALI that reflects inflammation, edema, histological abnormalities, physiological dysfunction characterize ALI. Using cecal slurry (CS) polymicrobial abdominal exposure hyperoxia (95%), we systematically varied timing dose CS injection, fluids antibiotics, hyperoxia. We found alone had...
Sepsis is a devastating disease with high morbidity and mortality no specific treatments. The pathophysiology of sepsis involves hyperinflammatory response release damage-associated molecular patterns (DAMPs), including adenosine triphosphate (ATP), from activated dying cells. Purinergic receptors by ATP have gained attention for their roles in sepsis, which can be pro- or anti-inflammatory depending on the context. Current data regarding role ATP-specific purinergic receptor P2X7 (P2X7R)...
Patients with Chronic Obstructive Pulmonary Disease often have persistent inflammation of the airways that lead to symptoms chronic bronchitis and airway obstruction. While it is known long term exposure cigarette smoke can cause inflammation, not clear if this a direct result tobacco or inflammation. We hypothesized recurrent prolonged inflammatory insult would in alterations lung mechanics characterized by obstruction.. To test independent effects on mechanics, C57Bl/6 8 week old male mice...