Gannon A. McDonough
A5094180562- RNA Research and Splicing
- Prion Diseases and Protein Misfolding
- Neurological diseases and metabolism
- Mitochondrial Function and Pathology
- Traumatic Brain Injury and Neurovascular Disturbances
- Epigenetics and DNA Methylation
- Single-cell and spatial transcriptomics
Harvard University
2024-2025
Brigham and Women's Hospital
2024-2025
Characterizing somatic mutations in the brain is important for disentangling complex mechanisms of aging, yet little known about mutational patterns different cell types. Here, we performed whole-genome sequencing (WGS) 86 single oligodendrocytes, 20 mixed glia, and 56 neurons from neurotypical individuals spanning 0.4–104 years age identified >92,000 single-nucleotide variants (sSNVs) small insertions/deletions (indels). Although both types accumulate linearly with age, oligodendrocytes...
Background: Clinical trials of anti-Aβ monoclonal antibodies in Alzheimer disease (AD) infer target engagement from Aβ positron emission tomography (PET) and/or fluid biomarkers such as cerebrospinal (CSF) Aβ42/40.However, these measure deposits indirectly incompletely.In contrast, postmortem neuropathologic assessments allow direct investigation treatment effects on brain and many other pathologic features.Methods: From a clinical trial dominantly inherited AD, we measured...
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...
Creutzfeldt-Jakob Disease (CJD), the most common human prion disease, is associated with pathologic misfolding of protein (PrP), encoded by
Abstract Background Chronic traumatic encephalopathy (CTE) is a neurodegenerative disease associated with repetitive head impact (RHI) although little known about its molecular pathogenesis. Previous studies of single neurons showed that private somatic mutations increase both during normal aging and in disorders, show diverse mutational patterns. Method We applied two orthogonal single‐nucleus whole‐genome sequencing (snWGS) methods to isolated from the prefrontal cortex 15 individuals CTE,...