A5054633516- Pluripotent Stem Cells Research
- Genetic Neurodegenerative Diseases
- Mitochondrial Function and Pathology
- DNA Repair Mechanisms
- CRISPR and Genetic Engineering
- RNA Interference and Gene Delivery
- Genomics and Chromatin Dynamics
- 3D Printing in Biomedical Research
- Single-cell and spatial transcriptomics
- Gene Regulatory Network Analysis
- Virus-based gene therapy research
- Biomedical Ethics and Regulation
- RNA modifications and cancer
- Advanced biosensing and bioanalysis techniques
- Viral Infectious Diseases and Gene Expression in Insects
- Cancer-related gene regulation
- MicroRNA in disease regulation
- Epigenetics and DNA Methylation
- Viral Infections and Immunology Research
- Cancer Genomics and Diagnostics
- Genomic variations and chromosomal abnormalities
- Neurogenetic and Muscular Disorders Research
- RNA Research and Splicing
- Parkinson's Disease Mechanisms and Treatments
Evotec (United States)
2021
Scripps Research Institute
2006-2017
Allen Institute for Brain Science
2014-2016
Allen Institute
2016
To investigate whether a histone deacetylase inhibitor (HDACi) would be effective in an vitro model for the neurodegenerative disease Friedreich ataxia (FRDA) and to evaluate safety surrogate markers of efficacy phase I clinical trial patients.We used human FRDA neuronal cell model, derived from patient induced pluripotent stem cells, determine 2-aminobenzamide HDACi (109) as modulator FXN gene expression chromatin modifications. patients were dosed 4 cohorts, ranging 30mg/day 240mg/day...
The genetic mutation in Friedreich ataxia (FRDA) is a hyperexpansion of the triplet-repeat sequence GAA·TTC within first intron FXN gene. Although yeast and reporter construct models for expansion have been reported, studies on FRDA pathogenesis therapeutic development are limited by availability an appropriate cell model which to study mechanism instability triplet repeats human genome. Herein, induced pluripotent stem cells (iPSCs) were generated from patient fibroblasts after transduction...
microRNAs (miRNAs) are crucial for cellular development and homeostasis. In order to better understand regulation of miRNA biosynthesis, we studied cleavage primary miRNAs by Drosha. While Drosha knockdown triggers an expected decrease many mature in human embryonic stem cells (hESC), a subset not reduced. Statistical analysis secondary structure fold change expression response showed that absence mismatches the central region hairpin, 5 9-12 nt from cutting site conferred decreased...
AbstractA polyamide-chlorambucil conjugate (1R-Chl) arrests a wide range of human cancer cell lines at the G2/M phase cycle and down-regulates histone H4c gene expression. However, an siRNA against mRNA causes G1/S arrest. Here, we reportthat 1R-Chl prior to arrest is result extensive DNA damage by 1R-Chl, which leads phosphorylation H2A.X serine 139, recruitment Nbs1 repair protein, cascade unknown events culminating with cdc2 tyrosine 15 abolishment kinase activity. A control polyamide-Chl...
Herein we present a protocol of reprogramming human adult fibroblasts into induced pluripotent stem cells (hiPSC) using retroviral vectors encoding Oct3/4, Sox2, Klf4 and c-myc (OSKM) in the presence sodium butyrate 1-3. We used this method to reprogram late passage (>p10) derived from Friedreich's ataxia patient (GM03665, Coriell Repository). The approach includes highly efficient transduction repetitive centrifugation virus-containing media. reprogrammed hiPSC colonies were identified live...
Herein we present a protocol of reprogramming human adult fibroblasts into induced pluripotent stem cells (hiPSC) using retroviral vectors encoding Oct3/4, Sox2, Klf4 and c-myc (OSKM) in the presence sodium butyrate 1-3. We used this method to reprogram late passage (>p10) derived from Friedreich's ataxia patient (GM03665, Coriell Repository). The approach includes highly efficient transduction repetitive centrifugation virus-containing media. reprogrammed hiPSC colonies were identified live...
Current methods for stably expressing recombinant protein therapeutics in CHO cells often rely on random or semi-random integration events which result a widely heterogeneous cell population. Consequently, significant portion of line development efforts involves extensive pool and clone screening to identify clones with high expression, growth, product quality. In this study, we developed two targeted systems that express levels cells. We first generated clonal lines enhanced green...