A5017352575- Neuroinflammation and Neurodegeneration Mechanisms
- Neuroscience and Neuropharmacology Research
- Neurogenesis and neuroplasticity mechanisms
- Genetic Neurodegenerative Diseases
- Nerve injury and regeneration
- Immune cells in cancer
- Alzheimer's disease research and treatments
- Barrier Structure and Function Studies
- Pluripotent Stem Cells Research
- Mitochondrial Function and Pathology
- Advanced Fluorescence Microscopy Techniques
- Neural dynamics and brain function
- Hereditary Neurological Disorders
- Single-cell and spatial transcriptomics
- Eicosanoids and Hypertension Pharmacology
- Cytokine Signaling Pathways and Interactions
- Inflammatory mediators and NSAID effects
- Axon Guidance and Neuronal Signaling
- Cancer, Stress, Anesthesia, and Immune Response
- Cellular transport and secretion
- Complement system in diseases
- Cell death mechanisms and regulation
- Advanced Electron Microscopy Techniques and Applications
- Melanoma and MAPK Pathways
- Pain Mechanisms and Treatments
Boston Children's Hospital
2014-2024
Harvard University
2014-2024
Broad Institute
2022-2024
University College London
2005-2014
Eisai (United Kingdom)
2005
SummaryThe radical response of peripheral nerves to injury (Wallerian degeneration) is the cornerstone nerve repair. We show that activation transcription factor c-Jun in Schwann cells a global regulator Wallerian degeneration. governs major aspects response, determines expression trophic factors, adhesion molecules, formation regeneration tracks and myelin clearance controls distinctive regenerative potential nerves. A key function repair program creation cell specialized support...
Abstract Huntington’s disease (HD) is a devastating monogenic neurodegenerative characterized by early, selective pathology in the basal ganglia despite ubiquitous expression of mutant huntingtin. The molecular mechanisms underlying this region-specific neuronal degeneration and how these relate to development early cognitive phenotypes are poorly understood. Here we show that there loss synaptic connections between cortex striatum postmortem tissue from patients with HD associated increased...
During cortical synaptic development, thalamic axons must establish connections despite the presence of more abundant intracortical projections. How thalamocortical synapses are formed and maintained in this competitive environment is unknown. Here, we show that astrocyte-secreted protein hevin required for normal connectivity mouse cortex. Absence results a profound, long-lasting reduction accompanied by transient increase excitatory connections. Three-dimensional reconstructions neurons...
Complement proteins facilitate synaptic elimination during neurodevelopmental pruning, but neural complement regulation is not well understood. CUB and Sushi Multiple Domains 1 (CSMD1) can regulate activity in vitro, expressed the brain, associated with increased schizophrenia risk. Beyond this, little known about CSMD1 including whether it regulates brain or otherwise plays a role neurodevelopment. We used biochemical, immunohistochemical, proteomic techniques to examine regional, cellular,...
Charcot–Marie–Tooth disease type 1A is the most frequent inherited peripheral neuropathy. It generally due to heterozygous inheritance of a partial chromosomal duplication resulting in over-expression PMP22. A key feature secondary death axons. Prevention axonal loss therefore an important target clinical intervention. We have previously identified signalling mechanism that promotes axon survival and prevents neuron mechanically injured nerves. This work suggested Schwann cells respond...
Although engulfment is a hallmark of microglia function, fully validated platforms that facilitate high-throughput quantification this process are lacking. Here, we present FEAST (Flow cytometric Engulfment Assay for Specific Target proteins), which enables interrogation in vivo synaptic material by brain resident macrophages at single-cell resolution. We optimize two different analyses: fluorescent inside live cells and engulfed endogenous proteins within fixed cells. To overcome...
Abstract Schizophrenia risk is associated with increased gene copy number and brain expression of complement component 4 ( C4 ). Because the system facilitates synaptic pruning, association has renewed interest in a hypothesis that excessive pruning contributes to schizophrenia pathogenesis. However, little known about regulation neural tissues or whether such could be relevant psychiatric illness. Intriguingly, common variation within CSMD1 , which encodes putative inhibitor, consistently...
Cyclooxygenase-2 (COX-2) is an enzyme that plays a pivotal role in peripheral inflammation and pain via the prostaglandin pathway. In central nervous system (CNS), COX-2 implicated neurodegenerative psychiatric disorders as potential therapeutic target biomarker. However, clinical studies with have yielded inconsistent results, partly due to limited mechanistic understanding of how activity relates CNS pathology. Therefore, developing positron emission tomography (PET) radiotracers for human...
Abstract Huntington’s disease (HD) is a devastating monogenic neurodegenerative characterized by early, selective pathology in the basal ganglia despite ubiquitous expression of mutant huntingtin. The molecular mechanisms underlying this region-specific neuronal degeneration and how these relate to development early cognitive phenotypes are poorly understood. Here, we show that there loss synaptic connections between cortex striatum postmortem tissue from HD patients associated with...