A5046258728- Nitric Oxide and Endothelin Effects
- Inflammatory mediators and NSAID effects
- Eicosanoids and Hypertension Pharmacology
- Hemoglobin structure and function
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Neonatal Health and Biochemistry
- Mitochondrial Function and Pathology
- Porphyrin Metabolism and Disorders
- AI in cancer detection
- Renin-Angiotensin System Studies
- Neuroscience of respiration and sleep
- Neuroendocrine regulation and behavior
- Technology Assessment and Management
- Protein Structure and Dynamics
- Pharmacogenetics and Drug Metabolism
- Heme Oxygenase-1 and Carbon Monoxide
- Electron Spin Resonance Studies
- Cardiovascular, Neuropeptides, and Oxidative Stress Research
- Biochemical Acid Research Studies
- Lysosomal Storage Disorders Research
- Bacillus and Francisella bacterial research
- Corporate Finance and Governance
- Neurological Disease Mechanisms and Treatments
- Career Development and Diversity
- COVID-19 diagnosis using AI
Institute of Cytology and Genetics
2025
University of Bridgeport
2016-2022
Connecticut Analytical Corporation (United States)
2021
Cornell University
2005-2018
Weill Cornell Medicine
2015-2018
Center for Vascular Biology Research
2006-2011
Emory University Hospital
2010
The Rogosin Institute
2005
Rockefeller University
2005
Mount Sinai Beth Israel
2005
Protein 3-nitrotyrosine (3-NT) formation is frequently regarded as a simple biomarker of disease, an irreversible posttranslational modification that can disrupt protein structure and function. Nevertheless, evidence 3-NT modifications may be site selective reversible, thus allowing for physiological regulation activity, has begun to emerge. We have previously reported cyclooxygenase (COX)-1 undergoes heme-dependent nitration Tyr(385), internal catalytically essential residue. In the present...
COPD (chronic obstructive pulmonary disease) is defined by a fixed expiratory airflow obstruction associated with disordered airways and alveolar destruction. caused cigarette smoking the third greatest cause of mortality in US. Forced volume 1 second (FEV1) only validated clinical marker COPD, but it correlates poorly features not sensitive enough to predict early onset disease. Using LC/MS global untargeted metabolite profiling serum samples from well-defined cohort healthy smokers (n =...
Rationale: Waterpipes, also called hookahs, are currently used by millions of people worldwide. Despite the increasing use waterpipe smoking, there is limited data on health effects smoking and no federal regulations regarding its use.Objectives: To assess human lung using clinical biological parameters in young, light-use smokers.Methods: We assessed light-use, waterpipe-only smokers comparison with lifelong nonsmokers cough sputum scores, function, chest high-resolution computed tomography...
The mechanism by which the inflammatory enzyme prostaglandin H(2) synthase-1 (PGHS-1) deactivates remains undefined. This study aimed to determine stabilizing parameters of PGHS-1 and identify factors leading deactivation nitric oxide species (NO(x)). Purified was stabilized when solubilized in beta-octylglucoside (rather than Tween-20 or CHAPS) reconstituted with hemin chloride hematin). Peroxynitrite (ONOO(-)) activated peroxidase site independently cyclooxygenase site. After ONOO(-)...
The airway epithelium is a complex pseudostratified multicellular layer lining the tracheobronchial tree, functioning as primary defense against inhaled environmental contaminants. major cell types of include basal, intermediate columnar, ciliated, and secretory. Basal cells (BCs) are proliferating stem/progenitor population that differentiate into other specialized during normal turnover repair. Given cigarette smoke delivers thousands xenobiotics high levels reactive molecules to lung...
Nitric oxide and its derivatives have been shown to both activate inhibit prostaglandin H2 synthase 1 (PGHS-1). We set out determine the mechanisms by which different nitrogen modulate PGHS-1 activity. To this end, we show that 3-morpholinosydnonimine hydrochloride (SIN-1), a compound capable of generating peroxynitrite, activates purified also stimulates PGE2 production in arterial smooth muscle cells presence exogenous arachidonic acid. The effect SIN-1 was abrogated superoxide...
In this study, we investigated the effects of various nitrogen oxide (NOx) species on extent prostaglandin H2 synthase-1 (PGHS-1) nitration in purified protein and vascular smooth muscle cells. We also examined PGHS-1 activity under these conditions found degree to correlate inversely with enzyme activity. addition, since NOx are thought invoke damage during pathogenesis atherosclerosis, human atheromatous tissue for nitration. Both peroxynitrite tetranitromethane induced Tyr PGHS-1, whereas...
Diminished nitric oxide (NO) bioactivity and enhanced peroxynitrite formation have been implicated as major contributors to atherosclerotic vascular dysfunctions. Hallmark reactions of include the accumulation 3-nitrotyrosine (3-NT) in proteins oxidation NO synthase (NOS) cofactor, tetrahydrobiopterin (BH(4)). The present study sought 1) quantify extent which 3-NT accumulates BH(4) becomes oxidized organs apolipoprotein E-deficient (ApoE(-/-)) mice 2) determine specific contribution...
Cyclooxygenase (COX)-2 and inducible nitric oxide (NO) synthase (iNOS) are responsive to a wide array of inflammatory stimuli, have been localized vascular smooth muscle cells (SMCs), intimately linked the progression disease, including atherosclerotic lesion formation. We others shown that production subsequent impact COX products appear be correlative with status NO synthesis. This study examined inflammation-driven on COX-2 expression in SMCs. Concurrent stimulation quiescent rat aortic...
Late infantile neuronal ceroid lipofuscinosis (CLN2 disease) is a rare lysosomal storage disorder caused by monogenetic deficiency of tripeptidyl peptidase-1 (TPP1). Despite knowledge that lipofuscin the hallmark disease product, relevant TPP1 substrate and its role in physiology/pathology unknown. We hypothesized untargeted metabolite profiling cerebrospinal fluid (CSF) could be used as an effective tool to identify disease-associated metabolic disruptions CLN2 disease, offering potential...
Eicosanoid production is reduced when the nitric oxide (NO·) pathway inhibited or inducible NO synthase gene deleted, indicating that NO· and arachidonic acid pathways are linked. We hypothesized peroxynitrite, formed by reaction of superoxide anion, may cause signaling events leading to release subsequent eicosanoid generation. Western blot analysis rat arterial smooth muscle cells demonstrated peroxynitrite (100–500 μM) 3-morpholinosydnonimine (SIN-1; 200 stimulate phosphorylation...
This study details a product development process that accurately predicts the successful implementation of new into market. evaluates stage multi-stage-gate system. It offers systematic and rational platform describes multiple phases allow for determination project viability at onset any small to medium process. These detail interconnected steps with feedback loop carry concept through conceptual (Phase I) generation “proof concept” or an alpha prototype allows initiation estimates cost,...
Mechanisms underlying the pathogenicity of diabetes insipidus mutations were probed by studying their effects on properties bovine oxytocin-related neurophysin. The G17V, ΔE47, G57S, G57R, and C67STOP each shown to have structural consequences that would diminish conformational stability folding efficiency precursors in which they incorporated, factors contributing origins these property changes identified. Effects dimerization folded proteins similarly analyzed. projected relative impact...
Nitric oxide (NO) is an important vasoactive molecule produced by three NO synthase (NOS) enzymes: neuronal (nNOS), inducible (iNOS), and endothelial NOS (eNOS). While eNOS contributes to blood vessel dilation that protects against the development of hypertension, iNOS has been primarily implicated as a disease-promoting isoform during atherogenesis. Despite this, may play physiological role via modulation cyclooxygenase thromboregulatory eicosanoid production. Herein, we examined in murine...
Accumulation of macrophages and smooth muscle cells in the vascular wall is critical for development atherosclerotic lesions. Although much known about factors that regulate macrophage recruitment to wall, ability growth cell lesion vivo unclear. Our previous studies demonstrated neurotrophins their receptors, Trk receptor tyrosine kinases, are potent chemotactic cells, expression brain-derived neurotrophic factor (BDNF) its cognate receptor, TrkB, upregulated human lesions.TrkB(+/-) mice on...
Prostaglandin biosynthesis is catalyzed by two spatially and functionally distinct active sites in cyclooxygenase (COX) enzymes. Despite the crucial role of COXs biology, molecular details regarding function regulation these enzymes are incompletely defined. Reactive nitrogen species, formed during oxidative stress, produce modifications that alter COX functionalities prostaglandin biosynthesis. We previously established COX-1 undergoes selective nitration on Tyr385 via a mechanism requires...
Tin protoporphyrin IX (SnPP) is being used in the treatment of hyperbilirubinemia. We have studied SnPP complex with equine myoglobin (EqMb) by 1H and 119Sn nuclear magnetic resonance spectroscopy (NMR) as a general model for interaction hemoproteins. The formed from EqMb, SnPP.EqMb, was found to essentially same porphyrin-binding pocket EqMbCO, including porphyrin orientation major form EqMbCO. NMR has been demonstrate that proximal His93F8-metal coordination likely be intact SnPP.EqMb....