A5018156812- Heat shock proteins research
- Endoplasmic Reticulum Stress and Disease
- Pluripotent Stem Cells Research
- Alzheimer's disease research and treatments
- Computational Drug Discovery Methods
- Groundwater flow and contamination studies
- Hydrology and Watershed Management Studies
- Protein Structure and Dynamics
- CRISPR and Genetic Engineering
- Soil and Unsaturated Flow
- Agricultural Innovations and Practices
- Remote Sensing in Agriculture
- RNA Research and Splicing
- Neurogenesis and neuroplasticity mechanisms
- Genetics, Aging, and Longevity in Model Organisms
- RNA regulation and disease
- Genomics and Chromatin Dynamics
- Polymer crystallization and properties
- Neuroinflammation and Neurodegeneration Mechanisms
- Coffee research and impacts
- Single-cell and spatial transcriptomics
- Agriculture and Rural Development Research
- Rocket and propulsion systems research
- Telomeres, Telomerase, and Senescence
- Cholinesterase and Neurodegenerative Diseases
Salk Institute for Biological Studies
2019-2024
La Jolla Alcohol Research
2023
California Polytechnic State University
2020
Cuesta College
2020
University of Wisconsin–Madison
2015-2019
Centro Agronomico Tropical de Investigacion y Ensenanza Catie
2010-2017
Deutsche Gesellschaft für Internationale Zusammenarbeit
2014
University of South Florida
1977-2011
USF Health Byrd Alzheimer's Institute
2008-2011
University of Tampa
2011
Abstract Telomeres are the protective nucleoprotein structures at end of linear eukaryotic chromosomes. Telomeres’ repetitive nature and length have traditionally challenged precise assessment composition individual human telomeres. Here, we present Telo-seq to resolve bulk, chromosome arm-specific allele-specific telomere lengths using Oxford Nanopore Technologies’ native long-read sequencing. resolves shortening in five population doubling increments reveals intrasample, arm-specific,...
Impaired cerebral glucose metabolism is a pathologic feature of Alzheimer's disease (AD), with recent proteomic studies highlighting disrupted glial in AD. We report that inhibition indoleamine-2,3-dioxygenase 1 (IDO1), which metabolizes tryptophan to kynurenine (KYN), rescues hippocampal memory function mouse preclinical models AD by restoring astrocyte metabolism. Activation astrocytic IDO1 amyloid β and tau oligomers increases KYN suppresses glycolysis an aryl hydrocarbon...
Alzheimer's disease and other tauopathies have recently been clustered with a group of nervous system disorders termed protein misfolding diseases. The common element established between these is their requirement for processing by the chaperone complex. It now clear that individual components system, such as Hsp70 Hsp90, exist in an intricate signaling network exerts pleiotropic effects on host substrates. Therefore, we endeavored to identify new compounds can specifically regulate family....
Imbalanced protein load within cells is a critical aspect for most diseases of aging. In particular, the accumulation proteins into neurotoxic aggregates common thread host neurodegenerative diseases. Our previous work demonstrated that age-related changes to cellular chaperone repertoire contributes abnormal buildup microtubule-associated tau accumulates in group termed tauopathies, being Alzheimer's disease. Here, we show Hsp90 cochaperone, FK506-binding 51 (FKBP51), which possesses both...
It has traditionally been thought that the pathological accumulation of tau in Alzheimer's disease and other tauopathies facilitates neurodegeneration, which turn leads to cognitive impairment. However, recent evidence suggests tangles are not entity responsible for memory loss, rather it is an intermediate species disrupts neuronal function. Thus, efforts discover therapeutics emphasize soluble reductions as well neuroprotection.Here, we found neuroprotection alone caused by methylene blue...
Highlights•Fast differentiation of astrocytes from human pluripotent stem cells (hPSCs)•NFIA or NFIA plus SOX9 overexpression facilitates astrocyte generation•Fast generation subtype-specific hPSCs•CRISPR/Cas9-engineered hPSCs for fast astrocytesSummaryDifferentiation (hPSCs) is a tedious and variable process. This hampers the study hPSC-generated in disease processes drug development. By using CRISPR/Cas9-mediated inducible expression hPSCs, we developed method to efficiently generate 4–7...
DNA repair within neurons Humans have only a limited capacity to generate new neurons. These cells thus need errors in the genome. To better understand this process, Reid et al. developed Repair-seq, method locate genome of stem cell–derived hotspots (DRHs) were more likely occur specific genomic features such as gene bodies well formations, open chromatin, and active regulatory regions. This showed that was enriched at sites involved neuronal function identity. Furthermore, proteomic data...
Molecular chaperones regulate the aggregation of a number proteins that pathologically misfold and accumulate in neurodegenerative diseases. Identifying ways to manipulate these disease models is an area intense investigation; however, translation results mammalian brain has progressed more slowly. In this study, we investigated ability one chaperones, heat shock protein 27 (Hsp27), modulate tau dynamics. Recombinant wild-type Hsp27 genetically altered version perpetually...
The microtubule-associated protein Tau plays a crucial role in regulating the dynamic stability of microtubules during neuronal development and synaptic transmission. In group neurodegenerative diseases, such as Alzheimer disease other tauopathies, conformational changes are associated with initial stages pathology. Folding into MC1 conformation, where amino acids at residues 7–9 interact 312–342, is one earliest pathological alterations disease. mechanism this change subsequent effect on...
Astrocytes display diverse morphologies in different regions of the central nervous system. Whether astrocyte diversity is attributable to developmental processes and bears functional consequences, especially humans, unknown. RNA-seq human pluripotent stem cell-derived regional astrocytes revealed distinct transcript profiles, suggesting differential properties. This was confirmed by calcium signaling as well effects on neurite growth blood-brain barrier formation. Distinct transcriptional...
Poly(ethylene terephthalate) (PET) copolymers containing 2,6-anthracenedicarboxylate structural units are modified by Diels−Alder reactions with maleimides. Low molecular weight bis(maleimide)s used to chain extend and cross-link the polymers. The resulting materials were characterized 1H NMR, UV−vis, DSC, dilute solution viscometry. reaction of low anthracenes maleimides is thermally reversible at 250 °C. However, reverse slow, PET−anthracene prone thermal decomposition these higher temperatures.
Members of the 70-kDa heat shock family can control and manipulate a host oncogenic client proteins. This role Hsp70 in both folding degradation these proteins makes it potential drug target for certain forms cancer. The phenothiazine compounds, as well flavonoid myricetin, was recently shown to inhibit Hsp70-ATPase activity, whereas members dihydropyrimidine stimulated ATPase function. Akt, major survival kinase, found be under regulation Hsp70, when activity increased or decreased by Akt...
The microtubule-associated protein tau, which becomes hyperphosphorylated and pathologically aggregates in a number of these diseases, is extremely sensitive to manipulations chaperone signaling. For example, Hsp90 inhibitors can reduce the levels tau transgenic mouse models tauopathy. Because this, we hypothesized that accessory proteins, termed co-chaperones, could also affect stability. Perhaps by identifying new therapeutics be designed specifically target proteins facilitate clearance....
How mutations in glial fibrillary acidic protein (GFAP) cause Alexander disease (AxD) remains elusive. We generated iPSCs from two AxD patients and corrected the GFAP to examine effects of mutant on human astrocytes. astrocytes displayed aggregates, recapitulating pathological hallmark AxD. RNA sequencing implicated endoplasmic reticulum, vesicle regulation, cellular metabolism. Corroborating this analysis, we observed enlarged heterogeneous morphology coupled with perinuclear localization...
Glial cells have increasingly been implicated as active participants in the pathogenesis of neurological diseases, but critical pathways and mechanisms controlling glial function secondary non-cell autonomous neuronal injury remain incompletely defined. Here we use models Alexander disease, a severe brain disorder caused by gain-of-function mutations GFAP, to demonstrate that misregulation GFAP leads activation mechanosensitive signaling cascade characterized Hippo pathway consequent...
Target-based drug discovery for Alzheimer's disease (AD) centered on modulation of the amyloid β peptide has met with limited success. Therefore, recent efforts have focused targeting microtubule-associated protein tau. Tau pathologically accumulates in more than 15 neurodegenerative diseases and is most closely linked postsymptomatic progression AD. We endeavored to identify compounds that decrease tau stability rather prevent its aggregation. An extract from Myrica cerifera...