A5081666255- Neuroinflammation and Neurodegeneration Mechanisms
- Neurogenesis and neuroplasticity mechanisms
- Alzheimer's disease research and treatments
- Neurological Disease Mechanisms and Treatments
- Immune cells in cancer
- MicroRNA in disease regulation
- Single-cell and spatial transcriptomics
- Bioinformatics and Genomic Networks
- RNA Research and Splicing
- Advanced Nanomaterials in Catalysis
- Mosquito-borne diseases and control
- Nuclear Receptors and Signaling
- Barrier Structure and Function Studies
- Cancer-related molecular mechanisms research
- Neonatal and fetal brain pathology
- Hemoglobin structure and function
- Multiple Sclerosis Research Studies
- Inflammation biomarkers and pathways
Neurosciences Institute
2022-2025
Stanford University
2022-2025
VA Palo Alto Health Care System
2023
Genetic association studies have demonstrated the critical involvement of microglial immune response in Alzheimer's disease (AD) pathogenesis. Phospholipase C-gamma-2 (PLCG2) is selectively expressed by microglia and functions many receptor signaling pathways. In AD, PLCG2 induced uniquely plaque-associated microglia. A genetic variant PLCG2, PLCG2P522R, a mild hypermorph that attenuates AD risk. Here, we identified loss-of-function variant, PLCG2M28L, confers an increased PLCG2P522R...
The blood–brain barrier (BBB) is highly specialized to protect the brain from harmful circulating factors in blood and maintain homeostasis1,2. endothelial glycocalyx layer, a carbohydrate-rich meshwork composed primarily of proteoglycans, glycoproteins glycolipids that coats BBB lumen, key structural component BBB3,4. This layer forms first interface between vasculature, yet little known about its composition roles supporting function homeostatic diseased states. Here we find dysregulated...
Myelination of neuronal axons is essential for nervous system development. requires dramatic cytoskeletal dynamics in oligodendrocytes, but how actin regulated during myelination poorly understood. We recently identified serum response factor (SRF)—a transcription known to regulate expression and regulators other cell types—as a critical driver the aged brain. Yet, major gap remains understanding mechanistic role SRF oligodendrocyte lineage cells. Here, we show that required autonomously...
Aging induces region-specific functional decline across the brain. The cerebellum, critical for motor coordination and cognitive function, undergoes significant structural changes with age. molecular mechanisms driving cerebellar aging, particularly role of glia, including microglia, remain poorly understood. Here, we used single-nuclei RNA sequencing (snRNA-seq), microglial bulk RNA-seq, multiplexed error-robust fluorescence in situ hybridization (MERFISH) to characterize transcriptional...
An in-depth understanding of the molecular processes composing aging is crucial to develop therapeutic approaches that decrease as a key risk factor for cognitive decline. Herein, we present spatio-temporal brain atlas (15 different regions) microRNA (miRNA) expression across mouse lifespan (7 time points) and two interventions composed 1009 samples. MiRNAs are promising targets, they silence genes by complementary base-pair binding messenger RNAs known mediate speed. We first established...
Summary Aging is the key risk factor for cognitive decline, yet molecular changes underlying brain aging remain poorly understood. Here, we conducted spatiotemporal RNA-seq of mouse brain, profiling 1,076 samples from 15 regions across 7 ages and 2 rejuvenation interventions. Our analysis identified a brain-wide gene signature in glial cells, which exhibited spatially defined magnitude. By integrating spatial single-nucleus transcriptomics, found that glia was particularly accelerated white...
Abstract Aging is a multifactorial and complex physiological process, affecting every organ with characteristic manifestations. Understanding the molecular mechanisms that drive aging processes crucial to targeting age-related disorders. Recent reports suggest severe post-infection syndromes can partially accelerate aging. However, underlying gene-encoded regulatory interplay, whether being shared or distinct between infection biology are poorly understood. Here, we employed spatial...
Summary Multiple sclerosis (MS) is an autoimmune disease associated with inflammatory demyelination in the central nervous system (CNS). Autologous hematopoietic cell transplantation (HCT) under investigation as a promising therapy for treatment-refractory MS. Here we identify reactive myeloid state chronic experimental encephalitis (EAE) mice and MS patients that surprisingly neuroprotection immune suppression. HCT EAE leads to enhancement of this state, well clinical improvement, reduction...
Summary Genetic association studies have demonstrated the critical involvement of microglial immune response in Alzheimer’s disease (AD) pathogenesis. Phospholipase C-gamma-2 (PLCG2) is selectively expressed by microglia and acts many receptor signaling pathways. In AD, PLCG2 induced uniquely plaque-associated microglia. A genetic variant , P522R a mild hypermorph that attenuates AD risk. We report identification variant, M28 L associated with loss-of-function confers increased an...
Aging is the key risk factor for loss of cognitive function and neurodegeneration but our knowledge molecular dynamics across aging brain very limited. Here we perform spatiotemporal RNA-seq mouse aging, encompassing 847 samples from 15 regions spanning 7 ages. We identify a brain-wide gene signature representing in glia with spatially-defined magnitudes. By integrating spatial single-nuclei transcriptomics, reveal that profoundly accelerated white matter compared to cortical areas. further...