A5017867930- Sphingolipid Metabolism and Signaling
- Retinal Diseases and Treatments
- Biomedical Research and Pathophysiology
- Peroxisome Proliferator-Activated Receptors
- Cellular transport and secretion
- DNA Repair Mechanisms
- Alzheimer's disease research and treatments
- Lipid metabolism and biosynthesis
- Cancer, Hypoxia, and Metabolism
- Neuroinflammation and Neurodegeneration Mechanisms
- Photosynthetic Processes and Mechanisms
- Lipid Membrane Structure and Behavior
- Microtubule and mitosis dynamics
- Circadian rhythm and melatonin
- Genomics and Chromatin Dynamics
- Ocular Surface and Contact Lens
- Ginger and Zingiberaceae research
- Nuclear Structure and Function
- Cell death mechanisms and regulation
- Pancreatic function and diabetes
- Diabetes Treatment and Management
- Cholesterol and Lipid Metabolism
- Polysaccharides and Plant Cell Walls
- Connective tissue disorders research
- melanin and skin pigmentation
University of Utah
2019-2024
University of Oklahoma Health Sciences Center
2013-2023
Dean McGee Eye Institute
2014-2023
University of Utah Health Care
2020
Oklahoma Medical Research Foundation
2007-2013
Ceramides in focus Excess calorie intake can ultimately lead to a metabolic syndrome that interferes with fat or lipid metabolism. There are many different types of lipids, and it has been widely debated which the true culprits underlying disorders. Chaurasia et al. report ceramides major contributor insulin resistance fatty liver disease (see Perspective by Kusminski Scherer). This appears be caused enzyme dihydroceramide desaturase 1 (DES1), is normally involved ceramide production...
In meiotic prophase, telomeres associate with the nuclear envelope and accumulate adjacent to centrosome/spindle pole form chromosome bouquet, a well conserved event that in Saccharomyces cerevisiae requires telomere protein Ndj1p. Ndj1p interacts Mps3p, SUN domain is required for spindle body duplication sister chromatid cohesion. Removal of Ndj1p-interaction from MPS3 creates an ndj1 Delta-like separation-of-function allele, Mps3p are codependent stable association telomeres. proteins...
Faithful chromosome segregation during meiosis requires that homologous chromosomes associate and recombine. Chiasmata, the cytological manifestation of recombination, provide physical link holds homologs together as a pair, facilitating their orientation on spindle at I. Formation most crossover (CO) events assistance group proteins collectively known ZMM. HFM1/Mer3 is in this required for normal progression recombination proper synapsis between number model organisms. Our work first study...
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 Autophagy, the highly conserved process of protein and organelle degradation, is suppressed in liver by obesity metabolic dysfunction‐associated fatty disease associated with development insulin resistance. We generated adult liver‐inducible ATG3 knockout mice ( Atg3 iLKO ) to characterize pathways linking hepatic autophagy homeostasis. Genetic loss leads a reduction 16‐h fasted glucose levels, decrease endogenous production rates, an increase serum amino acids across fed states....
Adiponectin, encoded by ADIPOQ, is an insulin-sensitizing, anti-inflammatory, and renoprotective adipokine that activates receptors with intrinsic ceramidase activity. We identified a family harboring 10-nucleotide deletion mutation in ADIPOQ cosegregates diabetes end-stage renal disease. This introduces frameshift exon 3, resulting premature termination codon disrupts translation of adiponectin's globular domain. Subjects the had dramatically reduced circulating adiponectin increased...
Mutations in the elongation of very long chain fatty acids 4 (ELOVL4) gene cause human Stargardt's macular dystrophy 3 (STGD3), a juvenile onset dominant form degeneration. To understand role ELOVL4 protein retinal function, several mouse models have been developed by using transgenic (TG), knock-in (Elovl4(+/mut)), and knockout (Elovl4(+/-)) approaches. Here we analyzed quantitatively its enzymatic products (very saturated acid [VLC-FA] VLC-polyunsaturated [VLC-PUFA]) retinas 8 to...
Farber Disease is a debilitating and lethal childhood disease of ceramide accumulation caused by acid ceramidase deficiency. The potent induction ligand-gated neutral activity promoted adiponectin may provide sufficient lowering ceramides to allow for the treatment Disease. In vitro, or receptor agonist treatments lowered total concentrations in human fibroblasts from patient with However, overexpression mouse model did not improve lifespan immune infiltration. Intriguingly, mice...
The purpose of this study was to investigate the role sphingosine kinase 1 (SphK1), which generates sphingosine-1-phosphate (S1P), in corneal neovascularization (NV). Wild-type (WT) and Sphk1 knockout (Sphk1−/−) mice received alkali-burn treatment induce NV by placing a 2 mm round piece Whatman No. filter paper soaked 1N NaOH on center cornea for 20 s. Corneal sphingolipid species were extracted identified using liquid chromatography/mass spectrometry (LC/MS). total number tip cells those...
Abstract Background Neurodegenerative disorders such as Alzheimer’s Disease (AD) are increasingly associated with irregular lipid accumulation. Dysfunction in the catabolism of sphingolipids leads to many neurodegenerative but has only recently garnered interest AD. Excess ceramide deposition been observed Aβ‐plaques, plasma, and cerebrospinal fluid AD patients mouse models. Ceramide‐lowering strategies have underexplored a treatment for may prove be beneficial target mitigating disease....
Summary Cancers of the gastrointestinal tract including esophageal adenocarcinomas, colorectal cancers, and cancers gastric cardia are common comorbidities obesity. Excessive delivery macronutrients to cells lining gut can increase one’s risk for these cancer by inducing imbalances in rate intestinal stem cell proliferation vs. differentiation, which produce polyps other aberrant growths. We demonstrate that serine palmitoyltransferase (SPT), diverts dietary fatty amino acids into...
Abstract Background Alzheimer’s Disease and other neurodegenerative disorders have been linked to metabolic associated with aberrant lipid deposition. Sphingolipids, such as ceramides, are among the most deleterious lipids that accumulate in AD brain. Increased ceramides measured post‐mortem brain samples abundant Aβ‐plaques. As biomarkers, plasma cerebrospinal fluid correlate risk. The potential of ceramide‐lowering strategies treat or prevent has underexplored. We hypothesize causal...