A5069256973- Neuroinflammation and Neurodegeneration Mechanisms
- Immune cells in cancer
- Neuroscience and Neuropharmacology Research
- Immune Response and Inflammation
- Neurogenesis and neuroplasticity mechanisms
- Multiple Sclerosis Research Studies
- interferon and immune responses
- Alzheimer's disease research and treatments
- Tryptophan and brain disorders
- Amyotrophic Lateral Sclerosis Research
- Barrier Structure and Function Studies
- Adenosine and Purinergic Signaling
- Peripheral Neuropathies and Disorders
- Chemokine receptors and signaling
- Phagocytosis and Immune Regulation
- Advanced Chemical Sensor Technologies
- Olfactory and Sensory Function Studies
- RNA regulation and disease
- Single-cell and spatial transcriptomics
- Hereditary Neurological Disorders
- Parkinson's Disease Mechanisms and Treatments
- Epigenetics and DNA Methylation
- Genetics and Neurodevelopmental Disorders
- Extracellular vesicles in disease
- Mosquito-borne diseases and control
Neuropsychiatric Research Institute
2019-2025
University of Massachusetts Chan Medical School
2016-2025
UMass Memorial Medical Center
2021
Abbott (United States)
2018
Boston Children's Hospital
2010-2016
Harvard University
2010-2016
UConn Health
2004-2009
Cre/loxP technology has revolutionized genetic studies and allowed for spatial temporal control of gene expression in specific cell types. Microglial biology particularly benefited because microglia historically have been difficult to transduce with virus or electroporation methods delivery. Here, we investigate five the most widely available microglial inducible Cre lines. We demonstrate varying degrees recombination efficiency, cell-type specificity, spontaneous recombination, depending on...
Microglial phagocytosis of apoptotic debris prevents buildup damage neighbor neurons and inflammatory responses. Whereas microglia are very competent phagocytes under physiological conditions, we report their dysfunction in mouse preclinical monkey models stroke (macaques marmosets) by transient occlusion the medial cerebral artery (tMCAo). By analyzing recently published bulk single cell RNA sequencing databases, show that was not explained transcriptional changes. In contrast, demonstrate...
Many factors contribute to nervous system dysfunction and failure regenerate after injury or disease. Here, we describe a previously unrecognized mechanism for injury. We show that neuronal causes rapid, irreversible, preferential proteolysis of the axon initial segment (AIS) cytoskeleton independently cell death degeneration, leading loss both ion channel clusters polarity. Furthermore, this is caused by AIS cytoskeletal proteins ankyrinG βIV spectrin calcium-dependent cysteine protease...
Microglia, the resident CNS macrophages, have been implicated in pathogenesis of Rett Syndrome (RTT), an X-linked neurodevelopmental disorder. However, mechanism by which microglia contribute to disorder is unclear and recent data suggest that do not play a causative role. Here, we use retinogeniculate system determine if how RTT mouse model, Mecp2 null (Mecp2(tm1.1Bird/y)). We demonstrate excessively engulfing, thereby eliminating, presynaptic inputs at end stages disease (≥P56 mice)...
Microglia, a resident CNS macrophage, are dynamic cells, constantly extending and retracting their processes as they contact functionally regulate neurons other glial cells. There is far less known about microglia–vascular interactions, particularly under healthy steady-state conditions. Here, we use the male female mouse cerebral cortex to show that higher percentage of microglia associate with vasculature during first week postnatal development compared older ages timing these associations...
Phagocytosis is a process in which cell engulfs material (entire cell, parts of debris, etc.) its surrounding extracellular environment and subsequently digests this material, commonly through lysosomal degradation. Microglia are the resident immune cells central nervous system (CNS) whose phagocytic function has been described broad range conditions from neurodegenerative disease (e.g., beta-amyloid clearance Alzheimer's disease) to development healthy brain synaptic pruning)(1-6). The...
Microglia play important roles in shaping the developing CNS, and at early stages they have been proposed to regulate progenitor proliferation, differentiation, neuronal survival. However, these studies reveal contradictory outcomes, highlighting complexity of cell–cell interactions. Here, we investigate microglia function during embryonic mouse retina development, where only microglia, progenitors, neurons are present. In both sexes, determine that primarily interact with retinal find...