A5006140621- Fatty Acid Research and Health
- Immune Response and Inflammation
- Eicosanoids and Hypertension Pharmacology
- Advanced Glycation End Products research
- Immune cells in cancer
- Carbohydrate Chemistry and Synthesis
- S100 Proteins and Annexins
- NF-κB Signaling Pathways
- Osteoarthritis Treatment and Mechanisms
- Retinopathy of Prematurity Studies
- Pregnancy-related medical research
- Analytical Chemistry and Chromatography
- Porphyrin and Phthalocyanine Chemistry
- Peroxisome Proliferator-Activated Receptors
- Synthesis of Indole Derivatives
- Inflammasome and immune disorders
- Retinal and Optic Conditions
- Antimicrobial Peptides and Activities
- Pharmacogenetics and Drug Metabolism
- Retinal Diseases and Treatments
- Alcohol Consumption and Health Effects
- Human Health and Disease
- Cholinesterase and Neurodegenerative Diseases
- Lipid metabolism and biosynthesis
- Connective Tissue Growth Factor Research
Brigham and Women's Hospital
2021-2025
Harvard University
2021-2025
Harvard University Press
2024-2025
University of Southern California
2019-2025
Mass General Brigham
2024
Southern California University for Professional Studies
2020
Hendrix College
2014-2017
University of Central Arkansas
2017
University of Arkansas for Medical Sciences
2017
Conway School of Landscape Design
2014
The onset of neurodegenerative diseases activates inflammation that leads to progressive neuronal cell death and impairments in cognition (Alzheimer's disease) sight (age-related macular degeneration [AMD]). How neuroinflammation can be counteracted is not known. In AMD, amyloid β-peptide (Aβ) accumulates subretinal drusen. the 5xFAD retina, we found early functional deficiencies (ERG) without photoreceptor (PRC) identified insufficiency biosynthetic pathways prohomeostatic/neuroprotective...
The resolution of the acute inflammatory response is governed by phagocytes actively clearing apoptotic cells and pathogens. Biosynthesis specialized pro-resolving mediators (SPMs) pivotal in inflammation via their roles innate immune cells. Resolvin E4 (RvE4: 5S,15S-dihydroxy-eicosapentaenoic acid) a newly uncovered member E-series resolvins biosynthesized from eicosapentaenoic acid (EPA) recently elucidated physiologic hypoxia. This new resolvin was termed RvE4 given its ability to...
Significance The resolution of the acute inflammatory response is an active, highly organized process essential for tissue regeneration, wound healing, and return to homeostasis that involves specialized proresolving mediators (SPMs). elucidation play roles in these processes general interest since many widely occurring diseases display unresolved inflammation their pathobiology. Here, we document pivotal role 4 S ,5 -epoxy-resolvin as intermediate biosynthesis resolvin D3 D4 identified a...
While the acute inflammatory response to harmful stimuli is protective, unrestrained neutrophil swarming drives collateral tissue damage and inflammation. Biosynthesized from omega-3 essential polyunsaturated fatty acids, resolvins are a family of signaling molecules produced by immune cells within resolution phase orchestrate return homeostasis. Understanding mechanisms that govern biosynthesis these potent gives insight into stimulating endogenous offers fresh opportunities for preventing...
Occupational exposure to engineered nanomaterials (ENMs) is increasing in the workplace and can impact human health. Amorphous silicon dioxide nanoparticles (SiO2 NPs) are widely produced respirable ENMs used commercial products. We have investigated their on lung inflammation resolution bacterial defense. Mice exposed SiO2 NPs, followed by bacteria, exhibited increased inflammation, proliferation, damage compared mice not NPs. NPs macrophage production of pro-inflammatory mediators...
The stereoselective total synthesis of an allylic epoxide-containing polyunsaturated fatty acid, in its triethylsilyl (TES) ether and methyl ester form, is described. Key features include a Sharpless enantioselective epoxidation to install the oxirane unit Wittig coupling reactions forge critical alkenyl configuration secure core carbon skeleton. deprotected epoxy acid was recently demonstrated play central role as precursor biologically active resolvins D1, D2, cysteinyl conjugate tissue...
Innervation sustains cornea integrity. Pigment epithelium-derived factor (PEDF) plus docosahexaenoic acid (DHA) regenerated damaged nerves by stimulating the synthesis of a new stereoisomer Resolvin D6 (RvD6si). Here, we resolved structure this lipid isolated from mouse tears after injured corneas were treated with PEDF + DHA. RvD6si was inhibited fluvoxamine, cytochrome P450 inhibitor, but not 15- or 5-LOX inhibitors, suggesting that 4- and 17-hydroxy DHA have an RR- SR-configuration. The...
Coumadin (rac-warfarin) is the most commonly used anticoagulant in world; however, its clinical use often challenging because of narrow therapeutic range and interindividual variations response. A critical contributor to uncertainty variability warfarin metabolism, which includes mostly oxidative but also reductive pathways. Reduction each enantiomer yields two alcohol isomers, corresponding four alcohols retain varying levels activity. Studies on kinetics reduction have lacked resolution...
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection that causes disease 2019 (COVID-19) has resulted in a pandemic affecting the most vulnerable society, triggering public health crisis and economic collapse around world. Effective treatments to mitigate this viral are needed. Since eye is route of virus entrance, we use an vivo rat model corneal inflammation as well human epithelial cells (HCEC) culture challenged with IFNγ models surface study issue. We explore ways...
The first total convergent synthesis of 4(S),5(S)-oxido-17(S)-hydroxy-6(E),8(E),10(Z),13(Z),15(E),19(Z)-docosahexaenoic acid (1) is described. reported led to confirmation the native epoxydocosahexaenoic as biosynthetic precursor lipid mediators resolvin D3 and D4. These potent enzymatic products docosahexaenoic (DHA) are important signaling molecules in resolution inflammation. A stereocontrolled chiral pool-based synthetic strategy was employed, with key features including epoxide...
Abstract Specialized pro‐resolving lipid mediators play key functions in the resolution of acute inflammatory response. Herein, we elucidate stereochemical structure new 4S,5R‐RCTR1, a cysteinyl‐resolvin, recently uncovered human leukocytes incubated with 4S,5S‐epoxy‐resolvin intermediate, using liquid chromatography–tandem mass spectrometry (LC–MS/MS) and ultra‐violet (UV) spectrophotometry. With this approach, physical properties mediator prepared by total organic synthesis were matched to...
Resolvin E4 (RvE4) belongs to the resolvin family of specialized pro-resolving mediators (SPMs). The resolvins are endogenously formed with both potent and anti-inflammatory biological activities have attracted considerable attention in inflammation research drug discovery. Hence, further metabolism is interest. Gaining knowledge about structure–function metabolites important due their interest drug-discovery efforts. For first time, total synthesis evaluations ω-20 hydroxylated metabolite...
Specialized proresolving mediators (SPMs) promote local macrophage efferocytosis but excess leukocytes early in inflammation require additional leukocyte clearance mechanism for resolution. Here, neutrophil mechanisms from localized acute were investigated mouse dorsal air pouches. 15-HEPE (15-hydroxy-5Z,8Z,11Z,13E,17Z-eicosapentaenoic acid) levels increased the exudates. Activated human neutrophils converted to lipoxin A
Specialized pro-resolving mediators (SPMs) promote resolution of inflammation, clear infections and stimulate tissue regeneration. These include resolvins, protectins, maresins. During self-resolving acute SPMs are produced have key functions activating endogenous response for returning to homeostasis. Herein, we addressed whether initiated with ongoing inflammation alter programs, if low-dose repetitive SPM regimen re-programs the response.
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection that causes disease 2019 (COVID-19) has resulted in a pandemic affecting the most vulnerable society, triggering public health crisis and economic tall around world. Effective treatments to mitigate this virus are needed. Since eye is route of entrance, we use an
The total synthesis of Resolvin D4 and its 17(