A5012208420- CRISPR and Genetic Engineering
- Pluripotent Stem Cells Research
- Mosquito-borne diseases and control
- Neuroinflammation and Neurodegeneration Mechanisms
- Invertebrate Immune Response Mechanisms
- Biomedical Ethics and Regulation
- DNA Repair Mechanisms
- Alzheimer's disease research and treatments
- Neuroscience and Neural Engineering
- Retinal Development and Disorders
- Geotechnical and construction materials studies
- Neurogenesis and neuroplasticity mechanisms
- Asphalt Pavement Performance Evaluation
- Cardiac electrophysiology and arrhythmias
- Infrastructure Maintenance and Monitoring
- RNA regulation and disease
- Inflammatory mediators and NSAID effects
- Genetic and Clinical Aspects of Sex Determination and Chromosomal Abnormalities
- Nuclear Receptors and Signaling
- Themes in Literature Analysis
- Mitochondrial Function and Pathology
- Amyotrophic Lateral Sclerosis Research
- biodegradable polymer synthesis and properties
- Reproductive Biology and Fertility
- RNA Interference and Gene Delivery
University of Wisconsin–Madison
2010-2023
University of Wisconsin System
2021
University of Iowa
2015
Madison Group (United States)
2010-2012
Medical Mission Institute
1985
Alzheimer's disease (AD) is a common neurodegenerative disorder and the leading cause of cognitive impairment. Due to insufficient understanding mechanisms, there are no efficient therapies for AD. Most studies have focused on neuronal cells, but astrocytes also been suggested contribute AD pathology. We describe here generation functional from induced pluripotent stem cells (iPSCs) derived patients with PSEN1 ΔE9 mutation, as well healthy gene-corrected isogenic controls. manifest hallmarks...
Significance Infection triggers the innate immune response in all metazoans, activating regulatory pathways that result expression of effector proteins, including potent antimicrobial peptides. These can also be activated brain by aging, stress, and injury. Although nominally protective, excessive neuroinflammatory responses may themselves contribute to neurodegenerative disease mechanisms remain unclear. We found hyperactivation immunity Drosophila as a mutation or bacterial injection...
To investigate the mechanistic basis for central nervous system (CNS) neurodegeneration in disease ataxia–telangiectasia (A-T), we analyzed flies mutant causative gene A-T mutated ( ATM ). encodes a protein kinase that functions to monitor genomic integrity of cells and control cell cycle, DNA repair, apoptosis programs. Mutation C-terminal amino acid Drosophila inhibited activity caused neuron glial death adult brain reduction mobility longevity. These data indicate reduced is sufficient...
Significance Traumatic brain injury (TBI) occurs when a strong jolt to the head causes damage cells, resulting in immediate and long-term consequences including physical, behavioral, cognitive problems. Despite importance of TBI as major health issue, our understanding underlying cellular molecular mechanisms is limited. To unravel these mechanisms, we have developed model fruit fly, Drosophila melanogaster , where can apply many powerful experimental tools. The main features human also...
CRISPR/Cas9 guided gene-editing is a potential therapeutic tool, however application to neurodegenerative disease models has been limited. Moreover, conventional mutation correction by would only be relevant for the small fraction of cases that are inherited. Here we introduce CRISPR/Cas9-based strategy in cell and animal edit endogenous amyloid precursor protein (APP) at extreme C-terminus reciprocally manipulate pathway, attenuating APP-β-cleavage Aβ production, while up-regulating...
Neurodegeneration is a hallmark of the human disease ataxia-telangiectasia (A-T) that caused by mutation A-T mutated (ATM) gene. We have analyzed Drosophila melanogaster ATM mutants to determine molecular mechanisms underlying neurodegeneration in A-T. Previously, we found upregulate expression innate immune response (IIR) genes and undergo central nervous system. Here, present evidence activation IIR cause mutants. Three lines indicate mutations activating Nuclear Factor-κB (NF-κB)...
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...
Reporter lines generated in human pluripotent stem cells can be highly useful for the analysis of specific cell types and lineages live cultures. We created first rod reporter line using CRISPR/Cas9 genome editing to replace one allele Neural Retina Leucine zipper (NRL) gene with an eGFP transgene WA09 embryonic (hESC) line. After confirming successful targeting, three-dimensional optic vesicle structures were produced examine specificity track differentiation culture. The NRL+/eGFP hESC...
Background: Inherited long QT syndrome type 2 results from variants in the KCNH2 gene encoding human Ether-à-go-go related 1 (hERG1) potassium channel. Two main isoforms, hERG1a and hERG1b, assemble to form tetrameric The N-terminal PAS (Per/Arnt/Sim) domain, present only on subunits, is a hotspot for pathogenic variants, but it unknown whether domain impact hERG1b expression contribute phenotype. We aimed use patient-specific induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs)...
Central norepinephrine (NE) neurons, located mainly in the locus coeruleus (LC), are implicated diverse psychiatric and neurodegenerative diseases an emerging target for drug discovery. To facilitate their study, we developed a method to generate 40-60% human LC-NE neurons from pluripotent stem cells. The approach depends on our identification of ACTIVIN A regulating transcription factors dorsal rhombomere 1 (r1) progenitors. In vitro generated display extensive axonal arborization; release...
Abstract Modeling age‐related neurodegenerative disorders with human stem cells are difficult due to the embryonic nature of cell‐derived neurons. We developed a chemical cocktail induce senescence iPSC‐derived neurons address this challenge. first screened small molecules that fibroblasts exhibit features characteristic aged fibroblasts. then optimized induced in and cortical without causing DNA damage. The utility “senescence cocktail” was validated motor derived from ALS patient iPSCs...
In this Extra View, we highlight recent Drosophila research that has uncovered a new role for the innate immune response. The indicates that, in addition to combating infection, response promotes neurodegeneration. Our publication (Petersen et al., 2012) reveals correlative relationship between and neurodegeneration model of human disease Ataxia-telangiectasia (A-T). We also found glial cells are responsible A-T model, work by others implicates Additionally, publications Chinchore al. (2012)...
Abstract Gonadotropin-releasing hormone (GnRH) neurons in the hypothalamus play a key role regulation of reproductive function. In this study, we sought an efficient method for generating GnRH from human embryonic and induced pluripotent stem cells (hESC hiPSC, respectively). First, found that exposure primitive neuroepithelial cells, rather than neuroprogenitor to fibroblast growth factor 8 (FGF8), was more effective neurons. Second, addition kisspeptin FGF8 further increased efficiency...
Seven human induced pluripotent stem cell (iPSC) lines were generated from fibroblasts three neonatal individuals using non-integrative reprogramming. Most control iPSCs are derived adults, so these meet the need for young individuals. Donors different ethnicities and provide unique genetic profiles. All have normal karyotypes, express markers, exhibit pluripotency, as assessed by capacity to differentiate into germ layers. These valuable study development, age-matched controls...
Reclaimed asphalt pavement (RAP) is a byproduct of roadway resurfacing. A limited amount RAP can be recycled into new hot-mix asphalt; the rest stockpiled. Some states allow use RAP–aggregate blends as base course material. Because RAP's low strength and susceptibility to creep deformation, Florida Department Transportation (DOT) excludes from being used for high-traffic areas. The research objective was determine whether characteristics could improved through compaction thereby make its...
The gradual accumulation of amyloid-β (Aβ) is a neuropathologic hallmark Alzheimer’s disease (AD); playing key role in progression. Aβ generated by the sequential cleavage amyloid precursor protein (APP) β- and γ-secretases, with BACE-1 (β-site APP cleaving enzyme-1) as rate limiting step 1–3 . CRISPR/Cas9 guided gene-editing emerging promising tool to edit pathogenic mutations hinder progression 4,5,6 However, few studies have applied this technology neurologic diseases 7–9 Besides...
CRISPR/Cas9 guided gene-editing is emerging as a promising therapeutic tool, however application to neurodegenerative diseases has been limited. Moreover, conventional ‘mutation correction’ by would only be relevant for the small fraction of cases that are inherited, and fresh ideas needed. Here we introduce CRISPR/Cas9-based strategy edit endogenous APP (amyloid precursor protein) at extreme C-terminus reciprocally manipulate amyloid pathway – attenuating β-cleavage Aβ production, while...
Summary Modeling age-related neurodegenerative disorders with human stem cells is difficult due to the embryonic nature of cell derived neurons. We developed a chemical cocktail induce senescence iPSC-derived neurons address this challenge. first screened small molecules that fibroblasts exhibit features characteristic aged fibroblasts. then optimized induced in and cortical without causing DNA damage. The utility “senescence cocktail” was validated motor from ALS patient iPSCs which...
Bibliography related to “The Teenage Brain”, presented at Teens and Tweens: Understanding How They Think; Providing Programs They’ll Love