A5046282174- Cancer-related cognitive impairment studies
- Genomics and Rare Diseases
- Genomic variations and chromosomal abnormalities
- Mitochondrial Function and Pathology
- CRISPR and Genetic Engineering
- Ferroptosis and cancer prognosis
- Histone Deacetylase Inhibitors Research
- Traumatic Brain Injury Research
- Neuroinflammation and Neurodegeneration Mechanisms
- Amyotrophic Lateral Sclerosis Research
- Cytomegalovirus and herpesvirus research
- DNA Repair Mechanisms
- Traumatic Brain Injury and Neurovascular Disturbances
- RNA regulation and disease
- Genetics and Neurodevelopmental Disorders
- Cholinesterase and Neurodegenerative Diseases
- Cancer Genomics and Diagnostics
- Single-cell and spatial transcriptomics
Sungkyunkwan University
2024-2025
Boston Children's Hospital
2019-2024
Harvard University
2019-2024
Broad Institute
2019-2024
Alzheimer's disease (AD) is an age-associated neurodegenerative disorder characterized by progressive neuronal loss and pathological accumulation of the misfolded proteins amyloid-β tau1,2. Neuroinflammation mediated microglia brain-resident macrophages plays a crucial role in AD pathogenesis1-5, though mechanisms which age, genes, other risk factors interact remain largely unknown. Somatic mutations accumulate with age lead to clonal expansion many cell types, contributing cancer non-cancer...
Abstract Chronic traumatic encephalopathy (CTE) is a neurodegenerative disease that linked to exposure repetitive head impacts (RHI), yet little known about its pathogenesis. Applying two single-cell whole-genome sequencing methods hundreds of neurons from prefrontal cortex 15 individuals with CTE, and 4 RHI without revealed increased somatic single-nucleotide variants in resembling pattern previously reported Alzheimer’s (AD). Furthermore, we discovered remarkably high burdens small...
Abstract Amyotrophic lateral sclerosis (ALS), frontotemporal dementia (FTD), and Alzheimer’s disease (AD) are common neurodegenerative disorders for which the mechanisms driving neuronal death remain unclear. Single-cell whole-genome sequencing of 429 neurons from three C9ORF72 ALS, six FTD, seven AD, twenty-three neurotypical control brains revealed significantly increased burdens in somatic single nucleotide variant (sSNV) insertion/deletion (sIndel) all conditions. Mutational signature...
Abstract While ATM loss-of-function has long been identified as the genetic cause of Ataxia Telangiectasia (A-T), how this mutation leads to selective and progressive degeneration cerebellar Purkinje granule neurons remains unclear. expression is enriched in microglia, resident immune cell central nervous system, throughout development adulthood. Microglial activation strongly implicated neurodegenerative disease observed rodent cellular models deficiency. Here, we find evidence prominent...
Abstract Low-level somatic mutations in the human brain are implicated various neurological disorders. The contribution of low-level to autism spectrum disorder (ASD), however, remains poorly understood. Here, we performed high-depth exome sequencing with an average read depth 559.3x 181 cortical, cerebellar, and peripheral tissue samples identify single nucleotide variants (SNVs) 24 ASD subjects 31 controls. We detected ~2.4 SNVs per region, a variant allele frequency (VAF) as low 0.3%....
Abstract Background Alzheimer’s disease (AD), an age‐associated neurodegenerative disorder, is characterized by progressive neuronal loss and the accumulation of misfolded proteins such as amyloid‐β tau. While neuroinflammation, mediated microglia brain‐resident macrophages, plays a pivotal role in AD pathogenesis, intricate interactions among age, genes, other risk factors remain elusive. Somatic mutations, known to accumulate with instigate clonal expansion across diverse cell types,...
Abstract Mutations that occur in cells of the body, called somatic mutations, cause human diseases including cancer and some neurological disorders 1 . In a recent study published Nature, Lee et al. 2 (hereafter “the study”) reported copy number gains APP gene, known risk locus Alzheimer’s disease (AD), neurons AD-patients controls (69% vs 25% with at least one gain on average). The authors argue mechanism these was integration mRNA into genome, creating what they genomic cDNA (gencDNA). We...