Shona W. Allen
A5079114881- Prion Diseases and Protein Misfolding
- Trace Elements in Health
- Neurological diseases and metabolism
- Single-cell and spatial transcriptomics
- Cell Image Analysis Techniques
- Gene Regulatory Network Analysis
- RNA regulation and disease
- Clusterin in disease pathology
- CRISPR and Genetic Engineering
- Medical Research and Treatments
- Folate and B Vitamins Research
- Pluripotent Stem Cells Research
- Virus-based gene therapy research
- Neural dynamics and brain function
University of California, Berkeley
2020-2024
Broad Institute
2024
Massachusetts General Hospital
2021-2023
Harvard University
2021-2022
The mammalian cortex is comprised of cells classified into types according to shared properties. Defining the contribution each cell type processes guided by essential for understanding its function in health and disease. We used transcriptomic epigenomic cortical taxonomies from mouse human define marker genes putative enhancers created a large toolkit transgenic lines enhancer AAVs selective targeting populations. report evaluation fifteen new driver lines, two reporter >800 different...
Prion protein (PrP) concentration controls the kinetics of prion replication and is a genetically pharmacologically validated therapeutic target for disease. In order to evaluate PrP as pharmacodynamic biomarker assess its contribution known disease risk factors, we developed plate-based immunoassay reactive across 6 species interest applicable brain cerebrospinal fluid (CSF). varied dramatically different regions in mice, cynomolgus macaques, humans. expression did not appear contribute...
To longitudinally characterize disease-relevant CSF and plasma biomarkers in individuals at risk for genetic prion disease up to conversion.
ABSTRACT We report the generation of a multimodal cell census and atlas mammalian primary motor cortex (MOp or M1) as initial product BRAIN Initiative Cell Census Network (BICCN). This was achieved by coordinated large-scale analyses single-cell transcriptomes, chromatin accessibility, DNA methylomes, spatially resolved morphological electrophysiological properties, cellular resolution input-output mapping, integrated through cross-modal computational analysis. Together, our results advance...
Genetic prion disease is a universally fatal and rapidly progressive neurodegenerative for which genetically targeted therapies are currently under development. Preclinical proofs of concept indicate that treatment before symptoms will offer outsize benefit. Though early paradigms be informed by the longitudinal biomarker trajectory mutation carriers, to date limited cases have been molecularly tracked from presymptomatic phase through symptomatic onset.
Objective: Prion disease is a rare, invariably fatal neurodegenerative characterized by rapid neuronal degeneration; Mutations to PRNP gene cause genetic prion (GPD). In animal models, microglial activation, astrocytosis, and release of neurofilament precede the onset frank symptoms (Sorce & Nuvolone 2020, Minikel 2020). humans at risk for GPD, prodromal pathology appears occur in only brief window prior symptom (Vallabh et al. Thompson 2021), but some data suggest that known mutation...
Abstract Background Blood‐based biomarkers offer the possibility of inexpensive, minimally invasive, and accessible diagnostic tools for Alzheimer’s Disease (AD). In context clinical trials, these hold promise subject stratification monitoring effects therapeutic interventions. The day‐to‐day variability measures must be robustly characterized to determine which blood‐based would most sensitive detecting treatment‐related responses. this study we evaluate biomarker performance in plasma...
Abstract Prion protein (PrP) concentration controls the kinetics of prion replication and is a genetically pharmacologically validated therapeutic target for disease. In order to evaluate PrP as pharmacodynamic biomarker assess its contribution known disease risk factors, we developed plate-based immunoassay reactive across six species interest applicable brain cerebrospinal fluid (CSF). varies dramatically between different regions in mice, cynomolgus macaques, humans. expression does not...