Gareth R. Howell
A5018525513- Alzheimer's disease research and treatments
- Neuroinflammation and Neurodegeneration Mechanisms
- Glaucoma and retinal disorders
- Bioinformatics and Genomic Networks
- Retinal Diseases and Treatments
- Retinal Development and Disorders
- Nuclear Receptors and Signaling
- Computational Drug Discovery Methods
- Neurological Disease Mechanisms and Treatments
- Adipose Tissue and Metabolism
- Neurological Disorders and Treatments
- GDF15 and Related Biomarkers
- Cerebrovascular and genetic disorders
- Complement system in diseases
- Metabolomics and Mass Spectrometry Studies
- Tryptophan and brain disorders
- Immune Cell Function and Interaction
- Folate and B Vitamins Research
- Neuroscience and Neuropharmacology Research
- Mitochondrial Function and Pathology
- Epigenetics and DNA Methylation
- Inflammation biomarkers and pathways
- Dementia and Cognitive Impairment Research
- Apelin-related biomedical research
- Biological Research and Disease Studies
Tufts University
2016-2025
University of Washington
2025
Jackson Laboratory
2015-2024
University of Maine
2019-2024
University of Rochester Medical Center
2024
University of California, Irvine
2022
Jackson Laboratories (India)
2021
Norwegian Womens Public Health Association
2020
Columbia University Irving Medical Center
2020
Karolinska Institutet
2020
Variants in triggering receptor expressed on myeloid cells 2 (TREM2) confer high risk for Alzheimer’s disease (AD) and other neurodegenerative diseases. However, the cell types mechanisms underlying TREM2’s involvement neurodegeneration remain to be established. Here, we report that TREM2 is up-regulated surrounding amyloid deposits AD mouse models human tissue. was detected CD45hiLy6C+ cells, but not P2RY12+ parenchymal microglia. In mice deficient TREM2, macrophages are virtually...
Here, we use a mouse model (DBA/2J) to readdress the location of insult(s) retinal ganglion cells (RGCs) in glaucoma. We localize an early sign axon damage astrocyte-rich region optic nerve just posterior retina, analogous lamina cribrosa. In this region, network astrocytes associates intimately with RGC axons. Using BAX-deficient DBA/2J mice, which retain all their RGCs, provide experimental evidence for insult within or very close nerve. show that proximal segments attached cell bodies...
Glaucoma is one of the most common neurodegenerative diseases. Despite this, earliest stages this complex disease are still unclear. This study was specifically designed to identify early glaucoma in DBA/2J mice. To do we used genome-wide expression profiling optic nerve head and retina a series computational methods. Eyes with no detectable by conventional assays were grouped into molecularly defined using unbiased hierarchical clustering. These represent temporally ordered sequence states....
The mechanisms underpinning concussion, traumatic brain injury, and chronic encephalopathy, the relationships between these disorders, are poorly understood. We examined post-mortem brains from teenage athletes in acute-subacute period after mild closed-head impact injury found astrocytosis, myelinated axonopathy, microvascular perivascular neuroinflammation, phosphorylated tau protein pathology. To investigate causal mechanisms, we developed a mouse model of lateral that uses momentum...
The ability to investigate therapeutic interventions in animal models of neurodegenerative diseases depends on extensive characterization the model(s) being used. There are numerous that have been generated study Alzheimer's disease (AD) and underlying pathogenesis disease. While transgenic instrumental understanding AD mechanisms risk factors, they limited degree characteristics displayed comparison with humans, full spectrum effects has yet be recapitulated a single mouse model. Model...
Glaucoma is a common ocular disorder that leading cause of blindness worldwide. It characterized by the dysfunction and loss retinal ganglion cells (RGCs). Although many studies have implicated various molecules in glaucoma, no mechanism has been shown to be responsible for earliest detectable damage RGCs their axons optic nerve. Here, we show leukocyte transendothelial migration pathway activated nerve head at stages disease an inherited mouse model glaucoma. This resulted proinflammatory...
A Tudor domain protein mediates posttranscriptional control of gene expression and is required for eye-lens development.
Glaucoma is a complex, multifactorial disease characterised by the loss of retinal ganglion cells and their axons leading to decrease in visual function. The earliest events that damage glaucoma are currently unknown. Retinal cell death appears be compartmentalised, with soma, dendrite axon changes potentially occurring through different mechanisms. There mounting evidence from other neurodegenerative diseases suggesting neuronal dendrites undergo prolonged period atrophy, including pruning...
Aging is the major risk factor for neurodegenerative diseases such as Alzheimer's disease, but little known about processes that lead to age-related decline of brain structures and function. Here we use RNA-seq in combination with high resolution histological analyses show aging leads a significant deterioration neurovascular including basement membrane reduction, pericyte loss, astrocyte dysfunction. Neurovascular was sufficient cause vascular leakage correlated strongly an increase...
Abstract Studies have assessed individual components of a western diet, but no study has the long-term, cumulative effects diet on aging and Alzheimer’s disease (AD). Therefore, we formulated first western-style that mimics fat, carbohydrate, protein, vitamin mineral levels diets. This was fed to C57BL/6J (B6) mice identify phenotypes may increase susceptibility AD, APP/PS1 mice, mouse model determine in AD. Astrocytosis microglia/monocyte activation were dramatically increased response...
Significance Exactly how high intraocular pressure (IOP) initiates glaucoma is unknown. Immune responses occur early in glaucoma, but whether they are induced by IOP or secondarily to retinal ganglion cell (RGC) dysfunction and molecular changes neurons glia remains This paper addresses these relationships provides a deeper understanding of this very common neurodegeneration. Overall, our data suggest that immune independent RGC thus triggered as more direct result IOP. Furthermore,...