A5036894949- Amyotrophic Lateral Sclerosis Research
- Alzheimer's disease research and treatments
- Neurogenesis and neuroplasticity mechanisms
- Neuroinflammation and Neurodegeneration Mechanisms
- Parkinson's Disease Mechanisms and Treatments
- RNA Research and Splicing
- Dementia and Cognitive Impairment Research
- Neurogenetic and Muscular Disorders Research
- Neuroscience and Neuropharmacology Research
- Mitochondrial Function and Pathology
- Single-cell and spatial transcriptomics
- Nerve injury and regeneration
- Axon Guidance and Neuronal Signaling
- RNA regulation and disease
- Genetics and Neurodevelopmental Disorders
- Neonatal and fetal brain pathology
- Neurological diseases and metabolism
- Immune cells in cancer
- Cancer-related gene regulation
- RNA modifications and cancer
- Autophagy in Disease and Therapy
- Prion Diseases and Protein Misfolding
- Genetic Neurodegenerative Diseases
- Cellular transport and secretion
- Advanced Fluorescence Microscopy Techniques
University of California, San Francisco
2016-2025
Broad Center
2016-2024
San Francisco VA Health Care System
2022-2024
University of San Francisco
2015-2024
Vanderbilt University
2024
University of California, Davis
2013-2024
Broad Institute
2016-2023
University of Maryland, College Park
2022-2023
Aix-Marseille Université
2023
UCLouvain
2023
Mutations at the steel locus (Sl) of mouse affect same cellular targets as mutations white spotting (W), which is allelic with c-kit proto-oncogene. We show that KL, a hematopoietic growth factor obtained from conditioned medium BALB/c 3T3 fibroblasts stimulates proliferation mast cells and early erythroid progenitors, specifically binds to receptor. The predicted amino acid sequence isolated KL-specific cDNA clones suggests KL synthesized an integral transmembrane protein. Linkage analysis...
A 'frontal variant of Alzheimer's disease' has been described in patients with predominant behavioural or dysexecutive deficits caused by disease pathology. The description this rare phenotype limited to case reports and small series, many clinical, neuroimaging neuropathological characteristics are not well understood. In retrospective study, we included 55 a behavioural-predominant presentation (behavioural disease) diagnosis high-likelihood (n = 17) and/or biomarker evidence pathology...
To characterize cognitive and behavioral features, physical findings, brain atrophy patterns in pathology-proven corticobasal degeneration (CBD) syndrome (CBS) with known histopathology.We reviewed clinical magnetic resonance imaging data all patients evaluated at our center either an autopsy diagnosis of CBD (n = 18) or CBS first presentation histopathology 40). Atrophy were compared using voxel-based morphometry.CBD was associated 4 syndromes: progressive nonfluent aphasia 5), variant...
Amyloid-β, a hallmark of Alzheimer’s disease, begins accumulating up to two decades before the onset dementia, and can be detected in vivo applying amyloid-β positron emission tomography tracers such as carbon-11-labelled Pittsburgh compound-B. A variety thresholds have been applied literature define compound-B positivity, but ability these detect early deposition is unknown, validation studies comparing post-mortem amyloid burden are lacking. In this study we first derived for positivity...
The decline of cognitive function has emerged as one the greatest health threats old age. Age-related is caused by an impacted neuronal circuitry, yet molecular mechanisms responsible are unknown. C1q, initiating protein classical complement cascade and powerful effector peripheral immune response, mediates synapse elimination in developing CNS. Here we show that C1q levels dramatically increase normal aging mouse human brain, much 300-fold. This was predominantly localized close proximity...
Building the human brain As develops, neurons migrate from zones of proliferation to their final locations, where they begin build circuits. Paredes et al. have discovered that shortly after birth, a group proliferates near ventricles migrates in chains alongside circulatory vessels into frontal lobes (see Perspective by McKenzie and Fishell). Young postnatally anterior cingulate cortex then develop features inhibitory interneurons. The number migratory cells decreases over first 7 months...
To characterize in vivo signatures of pathological diagnosis a large cohort patients with primary progressive aphasia (PPA) variants defined by current diagnostic classification.Extensive clinical, cognitive, neuroimaging, and neuropathological data were collected from 69 sporadic PPA, divided into 29 semantic (svPPA), 25 nonfluent (nfvPPA), 11 logopenic (lvPPA), 4 mixed PPA. Patterns gray matter (GM) white (WM) atrophy at presentation assessed tested as predictors using support vector...
To compare the diagnostic performance of PET with amyloid ligand Pittsburgh compound B (PiB-PET) to fluorodeoxyglucose (FDG-PET) in discriminating between Alzheimer disease (AD) and frontotemporal lobar degeneration (FTLD).Patients meeting clinical criteria for AD (n = 62) FTLD 45) underwent PiB FDG-PET. scans were classified as positive or negative by 2 visual raters blinded diagnosis, using a quantitative threshold derived from controls 25). FDG visually rated consistent FTLD,...
Glioblastoma is a devastating form of brain cancer. To identify aspects tumor heterogeneity that may illuminate drivers invasion, we created glioblastoma cell atlas with single-cell transcriptomics cancer cells mapped onto reference framework the developing and adult human brain. We find multiple GSC subtypes exist within single tumor. Within these GSCs, an invasive population similar to outer radial glia (oRG), fetal type expands stem niche in normal cortex. Using live time-lapse imaging...
Progranulin (PGRN) is a widely expressed secreted protein that linked to inflammation. In humans, PGRN haploinsufficiency major inherited cause of frontotemporal dementia (FTD), but how deficiency causes neurodegeneration unknown. Here we show loss results in increased neuron response injury the CNS. When exposed acutely 1-methyl-4-(2′-methylphenyl)-1,2,3,6-tetrahydrophine (MPTP), mice lacking (Grn–/–) showed more and microgliosis compared with wild-type mice. The exacerbated was due not...
Accurately predicting the underlying neuropathological diagnosis in patients with behavioural variant frontotemporal dementia (bvFTD) poses a daunting challenge for clinicians but will be critical success of disease-modifying therapies. We sought to improve pathological prediction by exploring clinicopathological correlations large bvFTD cohort. Among 438 whom was either top or an alternative possible clinical diagnosis, 117 had available autopsy data, including 98 primary lobar degeneration...
Autosomal dominant mutations of the RNA/DNA binding protein FUS are linked to familial amyotrophic lateral sclerosis (FALS); however, it is not clear how cause neurodegeneration. Using transgenic mice expressing a common FALS-associated mutation (FUS-R521C mice), we found that mutant proteins formed stable complex with WT and interfered normal interactions between histone deacetylase 1 (HDAC1). Consequently, FUS-R521C exhibited evidence DNA damage as well profound dendritic synaptic...