A5003278216- Trauma, Hemostasis, Coagulopathy, Resuscitation
- Nitric Oxide and Endothelin Effects
- Blood properties and coagulation
- Atherosclerosis and Cardiovascular Diseases
- Blood transfusion and management
- Diabetes Treatment and Management
- Sexual function and dysfunction studies
- Cardiovascular Health and Disease Prevention
- Cellular transport and secretion
- Birth, Development, and Health
- Glycosylation and Glycoproteins Research
- Renal function and acid-base balance
- Pregnancy and preeclampsia studies
- HER2/EGFR in Cancer Research
- Anesthesia and Pain Management
- Fungal and yeast genetics research
- Genital Health and Disease
- Sepsis Diagnosis and Treatment
- Receptor Mechanisms and Signaling
- Blood Coagulation and Thrombosis Mechanisms
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Protein Tyrosine Phosphatases
- Lipid Membrane Structure and Behavior
- Pancreatic function and diabetes
- Cellular Mechanics and Interactions
University of Missouri
2016-2025
Missouri College
2022
Einstein Healthcare Network
2018-2019
Fox Chase Cancer Center
2018-2019
Philadelphia University
2018
Einstein Medical Center Philadelphia
2014
University of California, San Diego
2001
The glycocalyx is a polysaccharide structure that protrudes from the body of cell. It primarily conformed glycoproteins and proteoglycans, which provide communication, electrostatic charge, ionic buffering, permeability, mechanosensation-mechanotransduction capabilities to cells. In blood vessels, endothelial projects into vascular lumen separates wall circulating blood. Such physical location allows number its components, including sialic acid, glypican-1, heparan sulfate, hyaluronan,...
Abstract Biocatalytic electrodes made of buckypaper were modified with PQQ‐dependent glucose dehydrogenase on the anode and laccase cathode. The enzyme assembled in a biofuel cell which was first characterized human serum solution then placed onto exposed rat cremaster tissue. Glucose oxygen dissolved blood used as fuel oxidizer, respectively, for implanted operation. steady‐state open circuitry voltage 140±30 mV short current 10±3 µA (current density ca. 5 cm −2 based geometrical electrode...
Abstract Aging of the vasculature is characterized by endothelial dysfunction and arterial stiffening, two key events in pathogenesis cardiovascular disease (CVD). Treatment with sodium glucose transporter 2 (SGLT2) inhibitors now known to decrease morbidity mortality type diabetes. However, whether SGLT2 inhibition attenuates vascular aging unknown. We first confirmed a cohort adult subjects that associated impaired function increased stiffness these variables are inversely correlated....
BACKGROUND: Plasma concentration of PAI-1 (plasminogen activator inhibitor-1) correlates with arterial stiffness. Vascular smooth muscle cells (SMCs) express PAI-1, and the intrinsic stiffness SMCs is a major determinant total We hypothesized that promotes SMC by regulating cytoskeleton pharmacological inhibition decreases aortic METHODS: PAI-039, specific inhibitor small interfering RNA were used to inhibit expression in cultured human SMCs. Effects on stiffness, F-actin (filamentous actin)...
ABSTRACT Objective In conduit arteries, aging and hypertension are associated with stiffening characterized by increased cytoskeletal F‐actin endothelial dysfunction. Herein, we determined if this also happens at the level of resistance vasculature. Methods We retrospectively compared mechanical structural characteristics small arteries isolated from older hypertensive younger normotensive (64.7 ± 2.8 vs. 32.1 1.9 years old) human subjects. The intersection was studied in mesenteric old (88...
Reversible and easy to use, temperature-sensitive (TS) mutations are powerful tools for studying gene function. However, TS alleles rare difficult generate identify, this has limited their use in most multicellular organisms. We have generated characterized 41 intein switches, Sce VMA that splice only at the permissive temperatures intact host proteins. At nonpermissive temperatures, they fail splice, resulting a loss of function proteins which reside. By inserting an switch into protein...
Consumption of excess fat and carbohydrate (Western diet, WD) is associated with alterations in the structural characteristics blood vessels. This vascular remodeling contributes to development cardiovascular disease, particularly as it affects conduit resistance arteries. Vascular often changes elastin-rich internal elastic lamina (IEL) activation transforming growth factor (TGF)-β. In addition, obesity type II diabetes have been increased serum neuraminidase, an enzyme known increase TGF-...
Increased arterial stiffness and vascular remodeling precede are consequences of hypertension. They also contribute to the development progression life-threatening cardiovascular diseases. Yet, there currently no agents specifically aimed at preventing or treating stiffening remodeling. Previous research indicates that smooth muscle actin polymerization participates in initial stages LIMK (LIM kinase) promotes F-actin formation stabilization via cofilin phosphorylation consequent...
Sphingosine-1-phosphate, a product of sphingomyelin degradation, is an important element signal transduction pathways that regulate cell proliferation and death. We have demonstrated additional roles for sphingosine-1-phosphate in growth multicellular development. The specific disruption Dictyostelium discoideum the lyase gene, which encodes enzyme catalyzes results mutant strain with aberrant morphogenesis, as well increase viability during stationary phase. absence affects multiple stages...
Yeast trans-Golgi network (TGN) membrane proteins maintain steady-state localization by constantly cycling to and from endosomes. In this study, we examined the trafficking itinerary molecular requirements for delivery of a model TGN protein A(F→A)–alkaline phosphatase (ALP) prevacuolar/endosomal compartment (PVC). A(F→A)-ALP was found reach PVC via early endosomes (EEs) with half-time ∼60 min. Delivery not dependent on either GGA or adaptor 1 (AP-1) type clathrin adaptors, which are thought...
Inward remodeling is the most prevalent structural change found in resistance arteries and arterioles of hypertensive individuals. Separate studies have shown that inward process requires transglutaminase activation polymerization actin. Therefore, we hypothesize induced via endogenous depends on actin cytoskeletal structures. To test this hypothesis, isolated cannulated rat cremaster were exposed to dithiothreitol (DTT) activate transglutaminases. DTT concentration-dependent...
To our knowledge, this is the first study to investigate involvement of ADAM17 in causing impaired insulin-induced vasodilation T2D. We provide evidence that activity increased vasculature patients with T2D and support notion ADAM17-mediated shedding endothelial IRα ectodomains a novel mechanism vascular insulin resistance. Our results highlight targeting may be potential therapeutic strategy correct resistance
Inward remodeling of the resistance vasculature is strongly associated with life-threatening cardiovascular events. Previous studies have demonstrated that both actin polymerization and activation transglutaminases mediate early stages transition from a structurally normal vessel to an inwardly remodeled one. Ex vivo further suggest few hours exposure vasoconstrictor agonists induces inward in absence changes intraluminal pressure. Here we report short, 10-min, topical serotonin (5-HT) +...
Children of mothers with gestational diabetes have greater risk developing hypertension but little is known about the mechanisms by which this occurs. The objective study was to test hypothesis that high maternal concentrations leptin during pregnancy, are present in and/or obesity, alter blood pressure, vascular structure and function offspring. Wildtype (WT) offspring hyperleptinemic, normoglycemic, Leprdb/+ dams were compared genotype matched WT-control dams. Vascular assessed male at 6,...
Maternal obesity and the use of assisted reproductive technologies (ART) are two suboptimal developmental environments that can lead to offspring cardiovascular disease. We hypothesized these independently synergistically adversely affect offspring's weight performance at ~7 weeks age. Mice were fed either 24% fat 17.5% high-fructose (HF) corn syrup or maintenance chow (5% fat; low-fat, no-fructose (LF)). Dams subdivided into no ART groups. embryos cultured in Whitten's medium transferred...
Degradation of the endothelial glycocalyx in type 2 diabetes (T2D) is thought to contribute impaired shear stress mechanotransduction, leading dysfunction and development cardiovascular disease. Herein, we tested hypothesis that restoration with dietary supplementation precursors (DSGP, containing glucosamine sulfate, fucoidan, superoxide dismutase, high molecular weight hyaluronan) improves function other indices vascular T2D. First, db/db mice, showed treatment DSGP (100 mg/kg/day) for...
Maternal obesity affects the incidence of cardiovascular disease and diabetes in offspring. Also use assisted reproductive technologies (ART) has been associated with deficiencies Obese women often suffer from infertility ART to achieve a pregnancy, but combined effects maternal on health offspring is not known. Here, we report within an obesogenic environment, consisting feeding western diet (WD) dams offspring, resistance artery function presence biomarkers juvenile mice Our results...
This study addressed whether phosphorylation regulates trafficking of yeast membrane proteins that cycle between the trans-Golgi network (TGN) and endosomal system. The TGN A-ALP, a model protein containing Ste13p cytosolic domain fused to alkaline phosphatase (ALP), Kex2p were found be phosphorylated in vivo. Mutation S13 residue on A-ALP Ala was block prevacuolar compartment (PVC), whereas S13D mutation generated mimic accelerated into PVC. shown by mass spectrometry phosphorylated. rate...
This work identifies neuraminidase as a key mediator of endothelial dysfunction in type 2 diabetes that may serve biomarker for impaired function and predictive development progression cardiovascular pathologies associated with (T2D). Data show intervention the inhibitor zanamivir at effective plasma concentrations represent novel pharmacological strategy restoring glycocalyx ameliorating dysfunction.