A5046522509- Alzheimer's disease research and treatments
- Pluripotent Stem Cells Research
- Epigenetics and DNA Methylation
- Fetal and Pediatric Neurological Disorders
- Genetic and Kidney Cyst Diseases
- Bioinformatics and Genomic Networks
- Protist diversity and phylogeny
- Genetic Mapping and Diversity in Plants and Animals
- Genomic variations and chromosomal abnormalities
- Nuclear Receptors and Signaling
- 14-3-3 protein interactions
- Cancer-related molecular mechanisms research
- Genomics and Rare Diseases
- Computational Drug Discovery Methods
University of California, San Diego
2020-2025
La Jolla Bioengineering Institute
2023-2024
Moores Cancer Center
2020
Abstract Background PSEN1, PSEN2, and APP mutations cause Alzheimer’s disease (AD) with an early age at onset (AAO) progressive cognitive decline. PSEN1 are more common generally have earlier AAO; however, certain a later AAO, similar to those observed in PSEN2 . Methods We examined whether endotypes exist across these AAO (~ 55 years) using hiPSC-derived neurons from familial (FAD) patients harboring A79V , N141I V717I mechanistically characterized by integrating RNA-seq ATAC-seq. Results...
Development of neural circuitry depends on the integration signaling pathways to coordinate specification, proliferation and differentiation cell types in right number, place, at time. Zinc finger protein 423 (Zfp423), a 30-zinc transcription factor, forms alternate complexes with components several developmental pathways, suggesting it as point signal during brain development. We previously showed that mice lacking Zfp423 have reduced cerebellar precursor cells, resulting complete loss...
<title>Abstract</title> Background Mutations in PSEN1, PSEN2, and APP can lead to Alzheimer’s disease (AD) with an early age at onset (AAO) hallmark progressive cognitive decline. These mutations are highly penetrant. Although PSEN1 more common usually have earlier AAO, certain cause a later similar PSEN2 mutations. We sought determine whether endotypes exist across these relatively late AAO. Methods generated hiPSC-derived neurons from patients harboring autosomal-dominant, familial (FAD)...
Abstract Background Early‐onset Alzheimer’s disease (EOAD) is a complex that occurs at an early age onset (AAO) before 65 years, constituting 5‐6% of all AD cases and remains poorly understood. Patient‐derived induced pluripotent stem cells (iPSCs) have been used to model different forms EOAD display heterogeneous mechanisms. Method We examined iPSC‐derived neurons from both familial harboring mutations in PSEN1 A79V , PSEN2 N141I APP V717I non‐familial patients AAO. RNA‐seq for as well...
ABSTRACT Zfp423 encodes a transcriptional regulatory protein that interacts with canonical signaling and lineage pathways. Mutations in mouse or its human ortholog ZNF423 are associated range of developmental abnormalities reminiscent ciliopathies, including cerebellar vermis hypoplasia other midline brain defects. Null mice have reduced viability most strain backgrounds. Here we show complete lethality on C57BL/6J background, dominant rescue backcrosses to any 13 partner strains,...
Abstract Zfp423 encodes a transcriptional regulatory protein that interacts with canonical signaling and lineage pathways. Mutations in mouse or its human ortholog ZNF423 are associated range of developmental abnormalities reminiscent ciliopathies, including cerebellar vermis hypoplasia other midline brain defects. Null mice have reduced viability most strain backgrounds. Here we show complete lethality on C57BL/6J background, dominant rescue backcrosses to any 13 partner strains,...
Abstract Non-familial Alzheimer’s disease (AD) occurring before 65 years of age is commonly referred to as early-onset (EOAD) and constitutes ~ 5–6% all AD cases (Mendez et al. in Continuum 25:34–51, 2019). While EOAD exhibits the same clinicopathological changes such amyloid plaques, neurofibrillary tangles (NFTs), brain atrophy, cognitive decline (Sirkis Mol Psychiatry 27:2674–88, 2022; Caldwell Brain 15:83, 2022) observed more prevalent late-onset (LOAD), patients tend have severe...