A5059891728- Retinal Development and Disorders
- Retinal Diseases and Treatments
- Fatty Acid Research and Health
- Retinoids in leukemia and cellular processes
- Peroxisome Proliferator-Activated Receptors
- Sphingolipid Metabolism and Signaling
- Photoreceptor and optogenetics research
- Cholesterol and Lipid Metabolism
- Antioxidant Activity and Oxidative Stress
- Photochromic and Fluorescence Chemistry
- Lipid metabolism and biosynthesis
- Eicosanoids and Hypertension Pharmacology
- RNA regulation and disease
- Cellular transport and secretion
- Mitochondrial Function and Pathology
- Receptor Mechanisms and Signaling
- Cancer, Hypoxia, and Metabolism
- Metabolism and Genetic Disorders
- Diet and metabolism studies
- Adipose Tissue and Metabolism
- Photosynthetic Processes and Mechanisms
- Music Technology and Sound Studies
- Neuroscience and Neuropharmacology Research
- Sperm and Testicular Function
- Connexins and lens biology
University of Oklahoma Health Sciences Center
2016-2025
Dean McGee Eye Institute
2013-2024
Pitié-Salpêtrière Hospital
2023
Sorbonne Université
2023
Assistance Publique – Hôpitaux de Paris
2023
University of Oklahoma
2003-2021
Oklahoma City University
2008-2014
Osaka University of Health and Sport Sciences
2011
Cleveland Clinic
2010
University of California, San Francisco
2010
Stargardt-like macular dystrophy (STGD3) is a dominantly inherited juvenile degeneration that eventually leads to loss of vision. Three independent mutations causing STGD3 have been identified in exon six gene named Elongation very long chain fatty acids 4 (ELOVL4). The ELOVL4 protein was predicted be involved acid elongation, although evidence for this and the specific step(s) it may catalyze remained elusive. Here, using gain-of-function approach, we provide direct compelling required...
Delta-6 desaturase-null mice ((-/-)) are unable to synthesize highly unsaturated fatty acids (HUFAs): arachidonic acid (AA), docosahexaenoic (DHA), and n6-docosapentaenoic (DPAn6). The (-/-) males exhibit infertility arrest of spermatogenesis at late spermiogenesis. To determine which HUFA is essential for spermiogenesis, a diet supplemented with either 0.2% (w/w) AA or DHA was fed wild-type ((+/+)) weaning until 16 weeks age (n = 3-5). A breeding success rate DHA-supplemented comparable...
Age-related macular degeneration (AMD) is the leading cause of blindness in elderly. While histopathology different disease stages well characterized, underlying progression, from early drusen stage to advanced that leads blindness, remains unknown. Here, we show photoreceptors (PRs) diseased individuals display increased expression two key glycolytic genes, suggestive a glucose shortage during disease. Mimicking aspects this metabolic profile PRs wild-type mice by activation mammalian...
Long-chain PUFAs (LC-PUFAs; C20–C22; e.g., DHA and arachidonic acid) are highly enriched in vertebrate retina, where they elongated to very-long-chain (VLC-PUFAs; C ≥28) by the elongation of fatty acids-4 (ELOVL4) enzyme. These acids play essential roles modulating neuronal function health. The relevance different lipid requirements rods cones disease processes, such as age-related macular degeneration, however, remains unclear. To better understand role LC-PUFAs VLC-PUFAs we investigated...
In recent years, detergent-resistant membranes (DRMs) have been isolated in vitro models of lipid rafts, from photoreceptor outer segments (ROS), and the localization a specific complement proteins has demonstrated. However, surprisingly little is known about composition these important membrane domains. The present study provides first characterization phospholipids fatty acids ROS-derived DRMs.Bovine ROS were incubated with 1% Triton X-100 at 4 degrees C subjected to density gradient...
Light-induced retinal degeneration (LIRD) in albino rats causes apoptotic photoreceptor cell death. Ceramide is a second messenger for apoptosis. We tested whether increases ceramide mediate apoptosis LIRD and if inhibition of synthesis protects the retina. Sprague-Dawley were exposed to 2,700 lux white light 6 h, levels its intermediary metabolites measured by GC-MS or electrospray ionization tandem mass spectrometry. Enzymes de novo biosynthetic sphingomyelinase pathways generation...
Abstract Pyruvate kinase M2 (PKM2) is a glycolytic enzyme that expressed in cancer cells. Its role tumor metabolism not definitively established, but investigators have suggested regulation of PKM2 activity can cause accumulation intermediates and increase flux through the pentose phosphate pathway. Recent evidence suggests also may non-metabolic functions, including as transcriptional co-activator gene regulation. We reported previously abundant photoreceptor cells mouse retinas. In present...
Necrotizing enterocolitis (NEC) is a neonatal intestinal disease associated with oxidative stress. The targets of peroxidation and the role innate epithelial antioxidant defense system are ill-defined. We hypothesized that stress in NEC correlates oxidized GSH redox potentials, lipid peroxidation, dysfunctional system. Methods: Intestinal samples from infants +/− were generated into enteroids incubated lipopolysaccharide (LPS) hypoxia to induce experimental NEC. HPLC assayed potentials....
We hypothesized that reduction/loss of very long chain PUFAs (VLC-PUFAs) due to mutations in the ELOngase fatty acid-4 (ELOVL4) protein contributes retinal degeneration autosomal dominant Stargardt-like macular dystrophy (STGD3) and age-related degeneration; hence, increasing VLC-PUFA retina these patients could provide some therapeutic benefits. Thus, we tested efficiency elongation C20-C22 PUFA by ELOVL4 determine which substrates are best precursors for biosynthesis VLC-PUFA. The was...
Preclinical studies suggest that diets rich in omega-3 polyunsaturated fatty acids (n-3 PUFAs) may be beneficial for prevention of pancreatic cancer. Nutritional intervention are often complex, and there is no clear evidence, without potential confounding factors, on whether conversion n-6 PUFAs to n-3 tissues would provide protection. Experiments were designed using acid desaturase (Fat-1) transgenic mice, which can convert PUFA FAs endogenously, determine the impact intraepithelial...
Autosomal-dominant Stargardt-like macular dystrophy [Stargardt3 (STGD3)] results from single allelic mutations in the elongation of very-long–chain fatty acids-like 4 ( ELOVL4 ), whereas recessive lead to skin and brain dysfunction. protein localizes endoplasmic reticulum, where it mediates condensation reaction catalyzing formation (VLC) (C-28 C-40) acids, saturated polyunsaturated (PUFA). The defective gene product is truncated at C terminus, leading mislocalization aggregation other...
Five to eight percent of the world population currently suffers from at least one autoimmune disorder. Despite multiple immune modulatory therapies for demyelinating diseases central nervous system, these treatments can be limiting subsets patients due adverse effects and expense. To circumvent barriers, we investigated a nutritional intervention in mice undergoing experimental encephalomyelitis (EAE), model autoimmune-mediated demyelination that induces visual motor pathologies similar...
Abstract Transmembrane protein 135 (TMEM135) is thought to participate in the cellular response increased intracellular lipids yet no defined molecular function for TMEM135 lipid metabolism has been identified. In this study, we performed a analysis of tissues from Tmem135 mutant mice and found striking reductions docosahexaenoic acid (DHA) across all tissues, indicating role production DHA. Since enzymes required DHA synthesis remain intact mice, hypothesized that involved export...
Metabolic dysfunction-associated steatohepatitis (MASH) is an advanced form of metabolic steatotic liver disease (MASLD) characterized by accumulation fats in liver, chronic inflammation, hepatocytic ballooning, and fibrosis. This study investigates the significance hepatic Aryl hydrocarbon Receptor (AhR) signaling cinnabarinic acid (CA)-mediated protection against MASH. Here, we report that livers high-fat, high-fructose, high-cholesterol diet-fed hepatocyte-specific knockout mice (AhR-hKO)...
Recent evidence suggests that ceramide metabolism plays an important role in retinal photoreceptor cell survival and apoptosis. The purpose of this study was to characterize sphingolipids the retina with special emphasis on very-long-chain-containing saturated (VLC-FA) polyunsaturated (VLC-PUFA) fatty acid-containing species. VLC-FAs VLC-PUFAs are synthesized by ELOVL4 protein, which is involved human Stargardt's macular dystrophy type 3 (STGD3).Total lipids were extracted from other...
Autosomal dominant Stargardt-like macular dystrophy (STGD3) is a juvenile-onset disease that caused by mutations in Elovl4 (elongation of very long fatty acids-4). The catalyzes the first step conversion C24 and longer acids (FAs) to long-chain FAs (VLC-FAs, ≥C26). Photoreceptors are particularly rich VLC polyunsaturated (VLC-PUFA). To explore role VLC-PUFAs photoreceptors, we conditionally deleted mouse retina.Proteins were analyzed Western blotting lipids gas chromatography (GC)-mass...
Lipids are essential components of the nervous system. However, functions very long-chain fatty acids (VLC-FA; ≥ 28 carbons) in brain unknown. The enzyme ELOngation Very Long-chain acids-4 (ELOVL4) catalyzes rate-limiting step biosynthesis VLC-FA (Agbaga et al., Proc Natl Acad Sci USA 105(35): 12843–12848, 2008; Logan J Lipid Res 55(4): 698–708, 2014), which we identified as saturated (VLC-SFA). Homozygous mutations ELOVL4 cause severe neuropathology humans (Ozaki JAMA Neurol 72(7): 797–805,...
Abstract Smith–Lemli–Opitz syndrome (SLOS) is a complex hereditary disease caused by an enzymatic defect in the last step of cholesterol biosynthesis. Progressive retinal degeneration occurs AY9944‐induced rat model SLOS, with biochemical and electroretinographic hallmarks comparable human disease. We evaluated alterations non‐sterol lipid components retina this model, compared age‐matched controls, using lipidomic analysis. The levels 16:0–22:6 18:0–22:6 phosphatidylcholine molecular...
Juvenile-onset autosomal dominant Stargardt-like macular dystrophy (STGD3) is caused by mutations in ELOVL4 (elongation of very long fatty acids-4), an elongase necessary for the biosynthesis chain acids (VLC-FAs ≥ C26). Photoreceptors are enriched with VLC polyunsaturated (VLC-PUFAs), which long-term survival rod photoreceptors. The purpose these studies was to determine effect deletion VLC-PUFAs on synaptic function retinas mice conditionally depleted (KO) Elovl4.Retina assessed wild-type...