ORCID Profile
0000-0001-5203-2205
Current Organisations
The University of Edinburgh
,
Institute of Genetics and Molecular Medicine
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Publisher: Springer Science and Business Media LLC
Date: 24-06-2020
Publisher: American Association for Cancer Research (AACR)
Date: 31-03-2023
DOI: 10.1158/0008-5472.22422090.V1
Abstract: Supplementary file comprising Supplementary Tables S1-S8. Table S1: list of antibodies used in this study Table S2: gene set from literature used for pathway analysis Table S3: list of significantly enriched pathways from GSEA analysis between primary tumour and regression site (low cell number RNA-seq) Table S4: qPCR primers used in this study Tables S5: list of shared upregulated pathways in superficial melanoma and low MITF patients Table S6: list of shared upregulated pathways in nodular melanoma and high MITF patients Table S7: list of pathways upregulated in paired comparison of zebrafish melanoma models Table S8: list of upregulated pathways from pairwise comparison between in idual clusters in single cell RNA-seq analysis.
Publisher: American Association for Cancer Research (AACR)
Date: 31-03-2023
DOI: 10.1158/0008-5472.22422090
Abstract: Supplementary file comprising Supplementary Tables S1-S8. Table S1: list of antibodies used in this study Table S2: gene set from literature used for pathway analysis Table S3: list of significantly enriched pathways from GSEA analysis between primary tumour and regression site (low cell number RNA-seq) Table S4: qPCR primers used in this study Tables S5: list of shared upregulated pathways in superficial melanoma and low MITF patients Table S6: list of shared upregulated pathways in nodular melanoma and high MITF patients Table S7: list of pathways upregulated in paired comparison of zebrafish melanoma models Table S8: list of upregulated pathways from pairwise comparison between in idual clusters in single cell RNA-seq analysis.
Publisher: Cold Spring Harbor Laboratory
Date: 08-12-2019
DOI: 10.1101/868679
Abstract: Cancers arise through the acquisition of oncogenic mutations and grow through clonal expansion 1, 2 . Here we reveal that most mutagenic DNA lesions are not resolved as mutations within a single cell-cycle. Instead, DNA lesions segregate unrepaired into daughter cells for multiple cell generations, resulting in the chromosome-scale phasing of subsequent mutations. We characterise this process in mutagen-induced mouse liver tumours and show that DNA replication across persisting lesions can generate multiple alternative alleles in successive cell isions, thereby increasing both multi-allelic and combinatorial genetic ersity. The phasing of lesions enables the accurate measurement of strand biased repair processes, the quantification of oncogenic selection, and the fine mapping of sister chromatid exchange events. Finally, we demonstrate that lesion segregation is a unifying property of exogenous mutagens, including UV light and chemotherapy agents in human cells and tumours, which has profound implications for the evolution and adaptation of cancer genomes.
Publisher: American Association for Cancer Research (AACR)
Date: 31-03-2023
DOI: 10.1158/0008-5472.22422093
Abstract: Supplementary File comprising of Supplementary Material and Methods, Supplementary References and Supplementary Figures S1-S7. Figure S1: IHC of melanoma and proliferation markers Figure S2: Images of fish used for bulk RNA-seq, Figure S3: Heatmaps of most variable genes and MITF target genes Figure S4: describes transcriptome comparison of the three melanoma models Figure S5: apoptosis at the site of melanoma regression Figure S6: fish used for low cell number and single cell RNA-seq Figure S7: MITF-independent cells present in residual disease and primary tumour.
Publisher: American Association for Cancer Research (AACR)
Date: 31-03-2023
DOI: 10.1158/0008-5472.C.6511122.V1
Abstract: Abstract The melanocyte-inducing transcription factor (MITF)–low melanoma transcriptional signature is predictive of poor outcomes for patients, but little is known about its biological significance, and animal models are lacking. Here, we used zebrafish genetic models with low activity of Mitfa (MITF-low) and established that the MITF-low state is causal of melanoma progression and a predictor of melanoma biological subtype. MITF-low zebrafish melanomas resembled human MITF-low melanomas and were enriched for stem and invasive (mesenchymal) gene signatures. MITF-low activity coupled with a p53 mutation was sufficient to promote superficial growth melanomas, whereas BRAF sup V600E /sup accelerated MITF-low melanoma onset and further promoted the development of MITF-high nodular growth melanomas. Genetic inhibition of MITF activity led to rapid regression recurrence occurred following reactivation of MITF. At the regression site, there was minimal residual disease that was resistant to loss of MITF activity (termed MITF-independent cells) with very low-to-no MITF activity or protein. Transcriptomic analysis of MITF-independent residual disease showed enrichment of mesenchymal and neural crest stem cell signatures similar to human therapy-resistant melanomas. Single-cell RNA sequencing revealed MITF-independent residual disease was heterogeneous depending on melanoma subtype. Further, there was a shared subpopulation of residual disease cells that was enriched for a neural crest G sub /sub -like state that preexisted in the primary tumor and remained present in recurring melanomas. These findings suggest that invasive and stem-like programs coupled with cellular heterogeneity contribute to poor outcomes for MITF-low melanoma patients and that MITF-independent subpopulations are an important therapeutic target to achieve long-term survival outcomes. Significance: This study provides a useful model for MITF-low melanomas and MITF-independent cell populations that can be used to study the mechanisms that drive these tumors as well as identify potential therapeutic options. /
Publisher: American Association for Cancer Research (AACR)
Date: 31-03-2023
DOI: 10.1158/0008-5472.22422093.V1
Abstract: Supplementary File comprising of Supplementary Material and Methods, Supplementary References and Supplementary Figures S1-S7. Figure S1: IHC of melanoma and proliferation markers Figure S2: Images of fish used for bulk RNA-seq, Figure S3: Heatmaps of most variable genes and MITF target genes Figure S4: describes transcriptome comparison of the three melanoma models Figure S5: apoptosis at the site of melanoma regression Figure S6: fish used for low cell number and single cell RNA-seq Figure S7: MITF-independent cells present in residual disease and primary tumour.
Publisher: American Association for Cancer Research (AACR)
Date: 15-11-2019
DOI: 10.1158/0008-5472.CAN-19-0037
Abstract: This study provides a useful model for MITF-low melanomas and MITF-independent cell populations that can be used to study the mechanisms that drive these tumors as well as identify potential therapeutic options.
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
No related grants have been discovered for Ava Khamseh.