A5091747215- MicroRNA in disease regulation
- Pluripotent Stem Cells Research
- Genetic Neurodegenerative Diseases
- Mitochondrial Function and Pathology
- CRISPR and Genetic Engineering
- Chromatin Remodeling and Cancer
- RNA Interference and Gene Delivery
- Neuroscience and Neuropharmacology Research
- Neurogenesis and neuroplasticity mechanisms
- RNA Research and Splicing
- Alzheimer's disease research and treatments
- Circular RNAs in diseases
- Neuroinflammation and Neurodegeneration Mechanisms
- Genomics and Chromatin Dynamics
- Genetics, Aging, and Longevity in Model Organisms
- Autophagy in Disease and Therapy
- Single-cell and spatial transcriptomics
- Neurological disorders and treatments
- Epigenetics and DNA Methylation
- Hereditary Neurological Disorders
- RNA modifications and cancer
- Cancer Mechanisms and Therapy
- Graph Theory and Algorithms
- Signaling Pathways in Disease
- Nuclear Receptors and Signaling
Washington University in St. Louis
2016-2025
Hope Center for Neurological Disorders
2022-2024
Cornell University
2023
University of Illinois System
2021
Center for Neuroscience and Regenerative Medicine
2020
Lawrence Livermore National Laboratory
2005-2013
New York University Langone Orthopedic Hospital
2012
Howard Hughes Medical Institute
2004-2011
Stanford University
2009-2011
Columbia University
2004-2010
Aging is a major risk factor in many forms of late-onset neurodegenerative disorders. The ability to recapitulate age-related characteristics human neurons culture will offer unprecedented opportunities study the biological processes underlying neuronal aging. Here, we show that using recently demonstrated microRNA-based cellular reprogramming approach, fibroblasts from postnatal near centenarian donors can be efficiently converted into maintain multiple age-associated signatures....
Late-onset Alzheimer's disease (LOAD) is the most common form of (AD). However, modeling sporadic LOAD that endogenously captures hallmark neuronal pathologies such as amyloid-β (Aβ) deposition, tau tangles, and loss remains an unmet need. We demonstrate neurons generated by microRNA (miRNA)-based direct reprogramming fibroblasts from individuals affected autosomal dominant AD (ADAD) in a three-dimensional environment effectively recapitulate key neuropathological features AD. Reprogrammed...
The Caenorhabditis elegans vulva is an important paradigm for cell-cell interactions in animal development. fates of six vulval precursor cells are patterned through the action epidermal growth factor receptor-mitogen-activated protein kinase (EGFR-MAPK) inductive signaling pathway, which specifies 1 degrees fate, and LIN-12/Notch lateral 2 fate. Here, we provide evidence that signal spatially graded initially activates EGFR-MAPK pathway prospective cells. Subsequently, this effect...
Many emerging large-scale data science applications require searching large graphs distributed across multiple memories and processors. This paper presents a breadth- first search (BFS) scheme that scales for random with up to three billion vertices 30 edges. Scalability was tested on IBM BlueGene/L 32,768 nodes at the Lawrence Livermore National Laboratory. obtained through series of optimizations, in particular, those ensure scalable use memory. We 2D (edge) partitioning graph instead...
During the development of vertebrate nervous system, neural progenitors divide, generate progeny that exit mitosis, and then migrate to sites where they elaborate specific morphologies synaptic connections. Mitotic in neurons is accompanied by an essential switch ATP-dependent chromatin regulatory complexes from progenitor Brg/Brm-associated factor (npBAF) neuron-specific nBAF part driven miR-9/9* miR-124. Recapitulating this microRNA/chromatin fibroblasts leads their direct conversion...
Cell-cell interactions and cross-talk between signaling pathways specify Caenorhabditis elegans vulval precursor cells (VPCs) to adopt a spatial pattern: central "1 degrees " VPC, in which epidermal growth factor receptor (EGFR)-mitogen-activated protein kinase (MAPK) activity is high LIN-12/Notch low, flanked by two "2 VPCs, EGFR-MAPK low. Here, we identify microRNA gene, mir-61, as direct transcriptional target of LIN-12 show that expression mir-61 promotes the 2 fate. We also vav-1,...
It is our view that the state of art in constructing a large collection graph algorithms terms linear algebraic operations mature enough to support emergence standard set primitive building blocks. This paper position defining problem and announcing intention launch an open effort define this standard.
Animal study.Development of an animal model for the study biochemical changes that occur in epidural space after intervertebral disc herniation.Although strong evidence inflammatory component exists, processes underlying pain herniation remain unknown.Epidural lavage was performed 48 rats L5 dorsal root ganglion exposure at baseline and 3, 6, or 24 hours placement autologous nucleus pulposus (NP) (N = 15), saline NP + interferon-γ antibody (anti-IFN-γ; N 18) directly onto ganglion. Multiplex...
ATAC-seq is widely used to measure chromatin accessibility and identify open regions (OCRs). OCRs usually indicate active regulatory elements in the genome are directly associated with gene network. The identification of differential (DARs) between different biological conditions critical determining activity elements. Differential analysis shares many similarities expression RNA-seq data. However, distribution signal intensity from that data, higher sensitivity required for DARs...
Charcot-Marie-Tooth disease type 2A (CMT2A) is an untreatable childhood peripheral neuropathy caused by mutations of the mitochondrial fusion protein, mitofusin (MFN) 2. Here, pharmacological activation endogenous normal mitofusins overcame dominant inhibitory effects CMT2A mutants in reprogrammed human patient motor neurons, reversing hallmark stasis and fragmentation independent causal MFN2 mutation. In mice expressing T105M, intermittent with a small molecule, MiM111, normalized...
The mechanisms underlying the selective regional vulnerability to neurodegeneration in Huntington's disease (HD) have not been fully defined. To explore role of astrocytes this phenomenon, we used single-nucleus and bulk RNAseq, lipidomics, HTT gene CAG repeat-length measurements, multiplexed immunofluorescence on HD control post-mortem brains. We identified genes that correlated with repeat length, which were enriched astrocyte genes, lipidomic signatures implicated poly-unsaturated fatty...