A5001513312- Retinal Development and Disorders
- Retinal Diseases and Treatments
- Glaucoma and retinal disorders
- Cellular transport and secretion
- Genomics and Chromatin Dynamics
- Retinoids in leukemia and cellular processes
- Developmental Biology and Gene Regulation
- Epigenetics and DNA Methylation
- RNA Research and Splicing
- Mitochondrial Function and Pathology
- Spectroscopy and Chemometric Analyses
- Neurogenesis and neuroplasticity mechanisms
- Adipose Tissue and Metabolism
- Spectroscopy Techniques in Biomedical and Chemical Research
- Congenital heart defects research
- Ubiquitin and proteasome pathways
- Growth Hormone and Insulin-like Growth Factors
- Lipid Membrane Structure and Behavior
- Metabolomics and Mass Spectrometry Studies
- Neuroinflammation and Neurodegeneration Mechanisms
- Photoreceptor and optogenetics research
- Neurological Disease Mechanisms and Treatments
- Photochromic and Fluorescence Chemistry
- Endoplasmic Reticulum Stress and Disease
- CRISPR and Genetic Engineering
University of California, Irvine
2020-2025
University of California, San Diego
2013-2022
Applied BioPhysics (United States)
2022
Atkins (United States)
2018-2020
Smith-Kettlewell Eye Research Institute
2020
Howard Hughes Medical Institute
2013-2018
University of Geneva
2004-2016
La Jolla Alcohol Research
2015
Indiana University School of Medicine
2015
Hôpital Ophtalmique Jules-Gonin
2006-2007
Abstract Lipids play crucial roles in many biological processes. Mapping spatial distributions and examining the metabolic dynamics of different lipid subtypes cells tissues are critical to better understanding their aging diseases. Commonly used imaging methods (such as mass spectrometry-based, fluorescence labeling, conventional optical imaging) can disrupt native environment cells/tissues, have limited or spectral resolution, cannot distinguish subtypes. Here we present a hyperspectral...
Methylation of the regulatory region elongation very-long-chain fatty acids-like 2 (ELOVL2) gene, an enzyme involved in long-chain polyunsaturated acids, is one most robust biomarkers human age, but critical question whether ELOVL2 plays a functional role molecular aging has not been resolved. Here, we report that Elovl2 regulates age-associated and anatomical vivo, focusing on mouse retina, with direct relevance to age-related eye diseases. We show decrease expression associated increased...
While most mammalian enhancers regulate their cognate promoters over moderate distances of tens kilobases (kb), some act in the megabase range. The sequence features enabling such extreme-distance enhancer-promoter interactions remain elusive. Here, we used
Elevation of intraocular pressure (IOP) due to trabecular meshwork (TM) dysfunction, leading neurodegeneration, is the pathological hallmark primary open-angle glaucoma (POAG). Impaired axonal transport an early and critical feature glaucomatous neurodegeneration. However, a robust mouse model that accurately replicates these human POAG features has been lacking. We report development characterization novel Cre-inducible expressing DsRed-tagged Y437H mutant myocilin (Tg.CreMYOCY437H). A...
Glaucoma, a blinding neurodegenerative disease, whose risk factors include elevated intraocular pressure (IOP), age, and genetics, is characterized by accelerated progressive retinal ganglion cell (RGC) death. Despite decades of research, the mechanism RGC death in glaucoma still unknown. Here, we demonstrate that genetic effect SIX6 variant (rs33912345, His141Asn) enhanced another major POAG gene, p16INK4a (cyclin-dependent kinase inhibitor 2A, isoform INK4a). We further show upregulation...
Abstract Experimental ocular hypertension induces senescence of retinal ganglion cells (RGCs) that mimics events occurring in human glaucoma. Senescence‐related chromatin remodeling leads to profound transcriptional changes including the upregulation a subset genes encode multiple proteins collectively referred as senescence‐associated secretory phenotype (SASP). Emerging evidence suggests presence these proinflammatory and matrix‐degrading molecules has deleterious effects variety tissues....
Aging, a universal process that affects all cells in an organism, is major risk factor for group of neuropathies called glaucoma, where elevated intraocular pressure one the known stresses affecting tissue. Our understanding molecular impact aging on response to stress retina very limited; therefore, we developed new mouse model approach this question experimentally. Here show susceptibility increases with age and primed chromatin level. We demonstrate ocular hypertension activates similar...
Adiponectin receptor 1 (ADIPOR1) is a lipid and glucose metabolism regulator that possesses intrinsic ceramidase activity. Mutations of the ADIPOR1 gene have been associated with nonsyndromic syndromic retinitis pigmentosa. Here, we show absence AdipoR1 in mice leads to progressive photoreceptor degeneration, significant reduction electroretinogram amplitudes, decreased retinoid content retina, reduced cone opsin expression. Single-cell RNA-Seq results indicate encoded most abundantly...
Photoreceptors rely on distinct membrane compartments to support their specialized function. Unlike protein localization, identification of critical differences in content has not yet been expanded lipids, due the difficulty isolating domain-specific samples. We have overcome this by using SMA coimmunopurify proteins and native lipids from two regions photoreceptor ROS disks. Each sample's copurified were subjected untargeted lipidomic fatty acid analysis. Extensive between center...
Colonies of the red harvester ant (Pogonomyrmex barbatus) differ in how they regulate collective foraging activity response to changes humidity. We used transcriptomic, physiological, and pharmacological experiments investigate molecular basis this ecologically important variation behavior among colonies. RNA sequencing forager brain tissue showed an association between colony differential expression transcripts related biogenic amine neurohormonal metabolism signaling. In field experiments,...
Abstract Impairment of mitochondrial structure and function is strongly linked to glaucoma pathogenesis. Despite the widely appreciated disease relevance dysfunction loss, molecular mechanisms underlying fragmentation metabolic stress in are poorly understood. We demonstrate here that glaucomatous retinal ganglion cells (RGCs) show loss A-kinase anchoring protein 1 (AKAP1), activation calcineurin (CaN) reduction dynamin-related (Drp1) phosphorylation at serine 637 (Ser637). These findings...
Glaucoma is a leading cause of blindness worldwide in individuals 60 years age and older. Despite its high prevalence, the factors contributing to glaucoma progression are currently not well characterized. Glia-driven neuroinflammation mitochondrial dysfunction play critical roles glaucomatous neurodegeneration. Here, we demonstrated that elevated intraocular pressure (IOP) significantly decreased apolipoprotein A-I binding protein (AIBP; gene name Apoa1bp) retinal ganglion cells (RGCs), but...
Mutations in the adiponectin receptor 1 gene (AdipoR1) lead to retinitis pigmentosa and are associated with age-related macular degeneration (AMD). This study explores effects of AdipoR1 deficiency mice, revealing a striking decline ω3 polyunsaturated fatty acids (PUFA), an increase ω6 FAs, elevated ceramides retina. The impairs peroxisome proliferator-activated α (PPARα) signaling, which is crucial for FA metabolism, particularly affecting proteins transport oxidation retina retinal...
Abstract Organismal aging has been associated with diverse metabolic and functional changes across tissues. Within the immune system, key features of physiological hematopoietic cell include increased fat deposition in bone marrow, impaired stem progenitor (HSPC) function, a propensity towards myeloid differentiation. This shift lineage bias can lead to pre-malignant marrow conditions such as clonal hematopoiesis indeterminate potential (CHIP) or cytopenias undetermined significance (CCUS),...
Abstract The Greenland shark ( Somniosus microcephalus ) is the longest-living vertebrate and inhabits extremely dim cold waters of Arctic deep sea. This has led to speculations that it may have lost functional vision. Here, we present genomic, transcriptomic, histological evidence retains an intact visual system well-adapted for life in light. Histology vitro opsin expression revealed adaptations typical deep-sea species, including densely packed, elongated rods a short-wavelength shift rod...