Project description:XPA is required for Nucleotide Excision Repair system, which could function to repair DNA damage induced by the UV. UV damage on the genomic DNA cannot be removed, thus persistence of damage could affect the transcriptional machinary. We used the microarray to investigate the global expression profiles in the XP-A and XP-V cells in the low dose of UVC comparing with fibroblast from healthy person. Human primary fibroblasts were developed from the skin of healthy person and two XP patients (XP-A and XP-V). We evaluated global expression profiles comparing the UVC-exposed (0.5J/m2, 5J/m2) with non-exposed sample.
Project description:This is a first-in-human multi-center study which will be conducted in advanced malignant solid tumors patients. The solid tumor type is limited to melanoma, colorectal, non-small-cell lung, and thyroid cancer with positive BRAF V600 mutation. This study is divided into three stages: Phase Ia: a dose-escalation phase of XP-102; Phase Ib: a dose-escalation and sample size expansion phase of XP-102 plus trametinib; Phase IIa: an expansion phase of XP-102 plus trametinib.
Project description:XPA is required for Nucleotide Excision Repair system, which could function to repair DNA damage induced by the UV. UV damage on the genomic DNA cannot be removed, thus persistence of damage could affect the transcriptional machinary. We used the microarray to investigate the global expression profiles in the XP-A and XP-V cells in the low dose of UVC comparing with fibroblast from healthy person.
Project description:Xeroderma Pigmentosum (XP) is a DNA repair disorder characterized by photosensitivity, resulting in occurrence of freckle-like pigmented maculae and depigmented maculae on sun-exposed areas. XP complementation group A (XP-A) is the most frequent type in Japan, and patients with XP-A present most severe cutaneous and neurological symptoms due to nucleotide excision repair deficiency. Here, we established induced pluripotent stem cells (iPSCs) derived from XP-A patients and successfully differentiated into melanocytes. To elucidate the pathophysiology of XP, we comprehensively analyzed the difference in gene expression between XP-A-iMCs and healthy-control-iPSC-derived melanocytes (HC-iMCs) 4 hours and 12 hours after irradiation with 30 J/m2 or 150 J/m2 of UV-B using microarray analysis.
Project description:The ditelocentric addition line CS-7EL of the spring wheat (Triticum aestivum) cultivar Chinese Spring (CS) contains the long arm of the chromosome 7E from Thinopyrum elongatum (CS-7EL), which confers high resistance to fusarium head blight. It is of great interest to breeders to integrate the resistance locus (loci) from Th. elongatum into commercial wheat varieties. The objectives of this study were to identify candidate genes expressed from the 7EL chromosome of CS-7EL, to develop 7EL-specific molecular markers, and to validate their usefulness to characterize recombination between one of the group 7 chromosomes of wheat and Th. elongatum. High-throughput sequencing of Fusarium graminearum-infected and control CS and CS-7EL cDNA libraries was performed using RNA-Seq. A stepwise bioinformatics strategy was applied to assemble the sequences obtained from RNA-Seq and to create a conservative list of candidate genes expressed from the foreign chromosome 7EL. PCR primer pairs were designed and tested for 135 candidate genes. A total of 48 expressed molecular markers specific for the chromosome 7EL were successfully developed. Screening of progenies from two BC1F2 families from the cross CS-7E(7D)×2*CSph1b showed that these markers are useful to characterize recombination events between the chromosomes 7D from wheat and 7E from Th. elongatum.
Project description:As the causative gene for cockayne syndrome, CSB has a well-characerized function in transcription-coupled nucleotide excision repair. However, the complex neurological abnormalities that affect CS patients can not be simply explained by the DNA repair defects. CSB is also involved in RNAP II transcription regulation. This study characterizes the gene expression signatures affected by CSB protein. Using Nimblegen microarray we identified differentially expressed genes in human fibroblasts derived from CS patients as compared to CSB reconstituted cell lines (wild type).
