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Your search keyword '"Lai, Wei-Yun"' showing total 23 results
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23 results on '"Lai, Wei-Yun"'

6. ALK signaling primes the DNA damage response sensitizing ALK-driven neuroblastoma to therapeutic ATR inhibition

Author

Borenäs, Marcus, primary, Umapathy, Ganesh, additional, Lind, Dan E., additional, Lai, Wei-Yun, additional, Guan, Jikui, additional, Johansson, Joel, additional, Jennische, Eva, additional, Schmidt, Alexander, additional, Kurhe, Yeshwant, additional, Gabre, Jonatan L., additional, Aniszewska, Agata, additional, Strömberg, Anneli, additional, Bemark, Mats, additional, Hall, Michael N., additional, Eynden, Jimmy Van den, additional, Hallberg, Bengt, additional, and Palmer, Ruth H., additional

Published
2023
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9. Abstract 3936: ALK fusion oncogene driven SERPINB4 expression enhances tumor survival in NSCLC

Author

Chuang, Tzu-Po, primary, Lai, Wei-Yun, additional, Gabre, Jonatan L., additional, Lind, Dan E., additional, Umapathy, Ganesh, additional, Bokhari, Abdulmalik A., additional, Bergman, Bengt, additional, Kristenson, Linnea, additional, Thorén, Fredrik B., additional, Le, Anh, additional, Doebele, Robert, additional, Eynden, Jimmy V., additional, Palmer, Ruth H., additional, and Hallberg, Bengt, additional

Published
2023
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13. ALK fusion NSCLC oncogenes promote survival and inhibit NK cell responses via SERPINB4 expression

Author

Chuang, Tzu-Po, primary, Lai, Wei-Yun, additional, Gabre, Jonatan L., additional, Lind, Dan E., additional, Umapathy, Ganesh, additional, Bokhari, Abdulmalik A., additional, Bergman, Bengt, additional, Kristenson, Linnea, additional, Thorén, Fredrik B., additional, Le, Anh, additional, Doebele, Robert C., additional, Van den Eynden, Jimmy, additional, Palmer, Ruth H., additional, and Hallberg, Bengt, additional

Published
2023
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21. Evolution of phenotypic variance in response to a novel hot environment.

Author

Lai, Wei‐Yun and Schlötterer, Christian

Subjects
*QUANTITATIVE genetics, *PHENOTYPES, *GENE expression, *DROSOPHILA, *BODY temperature regulation, *COLD adaptation
Abstract

Shifts in trait means are widely considered as evidence for adaptive responses, but the impact on phenotypic variance remains largely unexplored. Classic quantitative genetics provides a theoretical framework to predict how selection on phenotypic mean affects the variance. In addition to this indirect effect, it is also possible that the variance of the trait is the direct target of selection, but experimentally characterized cases are rare. Here, we studied gene expression variance of Drosophila simulans males before and after 100 generations of adaptation to a novel hot laboratory environment. In each of the two independently evolved populations, the variance of 125 and 97 genes was significantly reduced. We propose that the drastic loss in environmental complexity from nature to the laboratory may have triggered selection for reduced variance. Our observation that selection could drive changes in the variance of gene expression could have important implications for studies of adaptation processes in natural and experimental populations. [ABSTRACT FROM AUTHOR]

Published
2022
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22. Natural variation in Drosophilashows weak pleiotropic effects

Author

Christodoulaki, Eirini, Nolte, Viola, Lai, Wei-Yun, and Schlötterer, Christian

Abstract

Background: Pleiotropy describes the phenomenon in which a gene affects multiple phenotypes. The extent of pleiotropy is still disputed, mainly because of issues of inadequate power of analyses. A further challenge is that empirical tests of pleiotropy are restricted to a small subset of all possible phenotypes. To overcome these limitations, we propose a new measurement of pleiotropy that integrates across many phenotypes and multiple generations to improve power. Results: We infer pleiotropy from the fitness cost imposed by frequency changes of pleiotropic loci. Mixing Drosophila simulanspopulations, which adapted independently to the same new environment using different sets of genes, we show that the adaptive frequency changes have been accompanied by measurable fitness costs. Conclusions: Unlike previous studies characterizing the molecular basis of pleiotropy, we show that many loci, each of weak effect, contribute to genome-wide pleiotropy. We propose that the costs of pleiotropy are reduced by the modular architecture of gene expression, which facilitates adaptive gene expression changes with low impact on other functions.

Published
2022
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23. ALK signaling primes the DNA damage response sensitizing ALK-driven neuroblastoma to therapeutic ATR inhibition.

Author

Borenäs M, Umapathy G, Lind DE, Lai WY, Guan J, Johansson J, Jennische E, Schmidt A, Kurhe Y, Gabre JL, Aniszewska A, Strömberg A, Bemark M, Hall MN, Eynden JVD, Hallberg B, and Palmer RH

Subjects
Humans, Mice, Animals, Anaplastic Lymphoma Kinase genetics, Cell Proliferation, Cell Line, Tumor, DNA Repair, DNA Damage, Ataxia Telangiectasia Mutated Proteins genetics, Receptor Protein-Tyrosine Kinases metabolism, Neuroblastoma drug therapy, Neuroblastoma genetics, Neuroblastoma pathology
Abstract

High-risk neuroblastoma (NB) is a significant clinical challenge. MYCN and Anaplastic Lymphoma Kinase (ALK), which are often involved in high-risk NB, lead to increased replication stress in cancer cells, suggesting therapeutic strategies. We previously identified an ATR (ataxia telangiectasia and Rad3-related)/ALK inhibitor (ATRi/ALKi) combination as such a strategy in two independent genetically modified mouse NB models. Here, we identify an underlying molecular mechanism, in which ALK signaling leads to phosphorylation of ATR and CHK1, supporting an effective DNA damage response. The importance of ALK inhibition is supported by mouse data, in which ATRi monotreatment resulted in a robust initial response, but subsequent relapse, in contrast to a 14-d ALKi/ATRi combination treatment that resulted in a robust and sustained response. Finally, we show that the remarkable response to the 14-d combined ATR/ALK inhibition protocol reflects a robust differentiation response, reprogramming tumor cells to a neuronal/Schwann cell lineage identity. Our results identify an ability of ATR inhibition to promote NB differentiation and underscore the importance of further exploring combined ALK/ATR inhibition in NB, particularly in high-risk patient groups with oncogene-induced replication stress., Competing Interests: Competing interests statement:The authors declare no competing interest.

Published
2024
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