A5015024164- Retinal Development and Disorders
- Photoreceptor and optogenetics research
- Zebrafish Biomedical Research Applications
- Neurobiology and Insect Physiology Research
- Single-cell and spatial transcriptomics
- Retinopathy of Prematurity Studies
- Neuroscience and Neuropharmacology Research
- Glaucoma and retinal disorders
- Circadian rhythm and melatonin
- Retinal Diseases and Treatments
- CRISPR and Genetic Engineering
- Cell Image Analysis Techniques
- Ocular Oncology and Treatments
- Marine and coastal ecosystems
- Aquatic Ecosystems and Phytoplankton Dynamics
- Neuroscience and Neural Engineering
- Genomics and Rare Diseases
- melanin and skin pigmentation
- Neurogenesis and neuroplasticity mechanisms
- Retinal and Macular Surgery
- Neurotransmitter Receptor Influence on Behavior
- Music Technology and Sound Studies
- Genomics and Chromatin Dynamics
- RNA modifications and cancer
- Epigenetics and DNA Methylation
University of Washington
2011-2025
Johns Hopkins University
2015-2024
Johns Hopkins Medicine
2021
NOAA National Marine Fisheries Service Northwest Fisheries Science Center
2015
National Oceanic and Atmospheric Administration
2015
NOAA National Marine Fisheries Service
2015
Howard Hughes Medical Institute
2011-2013
Thyroid hormone in color vision development Cone photoreceptors the eye enable vision, responding to different wavelengths of light according what opsin pigments they express. Eldred et al. studied organoids that recapitulate human retina and found differentiation cone cells into their tuned subtypes was regulated by thyroid hormone. Cones expressing short-wavelength (S) developed first, cones long- medium-wavelength (L/M) later. The switch toward L/M depended on signaling through nuclear...
Trichromacy is unique to primates among placental mammals, enabled by blue (short/S), green (medium/M), and red (long/L) cones. In humans, great apes, Old World monkeys, cones make a poorly understood choice between M L cone subtype fates. To determine mechanisms specifying cones, we developed an approach visualize expression of the highly similar M- L-opsin mRNAs. M-opsin was observed before during early human eye development, suggesting that are generated adult tissue, early-developing...
Much of the molecular understanding synaptic pathology in Alzheimer9s disease (AD) comes from studies various mouse models that express familial AD (FAD)-linked mutations, often combinations. Most compare absolute magnitudes long-term potentiation (LTP) and depression (LTD) to assess deficits bidirectional plasticity accompanying FAD-linked mutations. However, LTP LTD are not static, but their induction threshold is adjusted by overall neural activity via metaplasticity. Hence LTP/LTD...
With a critical need for more complete
Human pluripotent stem cells (PSCs) represent a powerful tool to investigate human eye development and disease. When grown in 3D, they can self-assemble into laminar organized retinas; however, variation the size, shape composition of individual organoids exists. Neither microenvironment nor timing critical growth factors driving retinogenesis are fully understood. To explore early retinal development, we developed SIX6-GFP reporter that enabled systematic optimization conditions promote...
The mechanisms governing the generation of neuronal subtypes at distinct times and proportions during human retinal development are poorly understood. While thyroid hormone (TH) signaling specifies cone photoreceptor subtypes, how this regulation changes over time remains unclear. To address question, we studied expression function type 3 iodothyronine deiodinase (DIO3), an enzyme that degrades TH, in organoids. We show DIO3 is a master regulator developmental timing cell fate stability....
The striatum is composed predominantly of medium spiny neurons (MSNs) that integrate excitatory, glutamatergic inputs from the cortex and thalamus, modulatory dopaminergic ventral midbrain to influence behavior. Glutamatergic activation AMPA, NMDA, metabotropic receptors on MSNs important for striatal development function, but roles each these receptor classes remain incompletely understood. Signaling through NMDA-type glutamate (NMDARs) in has been implicated various motor appetitive...
Abstract Resolving the molecular basis of a Mendelian condition (MC) remains challenging owing to diverse mechanisms by which genetic variants cause disease. To address this, we developed synchronized long-read genome, methylome, epigenome, and transcriptome sequencing approach, enables accurate single-nucleotide, insertion-deletion, structural variant calling diploid de novo genome assembly, permits simultaneous elucidation haplotype-resolved CpG methylation, chromatin accessibility,...
With a critical need for more complete
Nervous systems are incredibly diverse, with myriad neuronal subtypes defined by gene expression. How binary and graded fate characteristics patterned across tissues is poorly understood. Expression of opsin photopigments in the cone photoreceptors mouse retina provides an excellent model to address this question. Individual cones express S-opsin only, M-opsin or both M-opsin. These cell populations along dorsal-ventral axis, greater expression dorsal region ventral region. Thyroid hormone...
Photoreception, a form of sensory experience, is essential for normal development the mammalian visual system. Detecting photons during prerequisite system function - from vision's first synapse at cone pedicle and maturation retinal vascular networks, to transcriptional establishment cell types within cortex. Consistent with this theme, we find that lighting environment regulates developmental rod photoreceptor apoptosis via OPN4-expressing intrinsically photosensitive ganglion cells...
Behavioral sensitization to psychostimulants such as amphetamine (AMPH) is associated with synaptic modifications that are thought underlie learning and memory. Because AMPH enhances extracellular dopamine in the striatum where glutamate signaling essential for learning, one might expect molecular morphological changes occur response AMPH, including plasticity, would affect learning. To ascertain whether affects we tested wild-type mice lacking NMDA receptor striatal medium spiny neurons...
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Non-mammalian vertebrates maintain a proliferative stem cell population at the far periphery of their retina called ciliary marginal zone (CMZ), which gives rise to all retinal types and contributes regeneration upon injury. Humans do not CMZ into adulthood; however, it is known how long in development this region continues generate new neurons. Here, we identify cells peripheral fetal human that proliferate after rest quiescent. Single RNA-sequencing EdU tracing late time points reveal has...
Abstract The mechanisms that generate patterns of cell types unique to humans are poorly understood. In the central region human retina, high-acuity foveola is notable, in part, for its dense packing green (M) and red (L) cones absence blue (S) cones. To identify promote M/L suppress S cone patterning foveola, we examined fetal retinas differentiated retinal organoids. During development, sparse S-opsin-expressing initially observed foveola. Later contains a mix either co-express S-...
Abstract The mechanisms underlying the specification of diverse neuronal subtypes within human nervous system are largely unknown. blue (shortwavelength/S), green (medium-wavelength/M) and red (long-wavelength/L) cone photoreceptors retina enable high-acuity daytime vision trichromatic color perception. Cone specified in a poorly understood two-step process, with first decision between S L/M fates, followed by L M fates. To determine mechanism controlling vs. we studied differentiation...
Abstract Trichromacy is unique to primates among mammals, enabled by blue (short/S), green (medium/M), and red (long/L) cones. In humans Old World monkeys, cones make a poorly understood choice between M L cone subtype fates. To determine mechanisms specifying cones, we developed an approach visualize expression of the highly similar - opsin mRNAs. , but not was observed during early human eye development, suggesting that are generated before adult tissue, early-developing central retina...