Scholarship 23/18183-6 - Camptotecina, Glioma - BV FAPESP
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Investigation of HJURP functions in controlling replicative stress and cell proliferation after treatment with camptothecin

Grant number: 23/18183-6
Support Opportunities:Scholarships in Brazil - Scientific Initiation
Start date until: June 01, 2024
End date until: December 31, 2024
Field of knowledge:Biological Sciences - Morphology - Cytology and Cell Biology
Principal Investigator:Valeria Valente
Grantee:Luma Teles Vitale
Host Institution: Faculdade de Ciências Farmacêuticas (FCFAR). Universidade Estadual Paulista (UNESP). Campus de Araraquara. Araraquara , SP, Brazil

Abstract

Recent studies seek a better molecular characterization of tumors in order to understand the complexity of tumor biology and discover new genetic markers associated with their occurrence and progression, these markers may represent new therapeutic targets and/or prognosis prediction. The protein HJURP (Holliday Junction Recognition Protein), whose classic function is to act as a chaperone for CENP-A (Centromeric Protein A), has been associated with the development of different types of tumors. A strong correlation has been observed between high HJURP levels and worse prognosis. Thus, excess of HJURP in tumor cells is associated with more aggressive behavior in different types of cancer, which makes it an interesting target for potential oncological therapies. Additionally, our group demonstrated the role of HJURP in repairing damage caused by ionizing radiation in glioma cells, with a gain in radiation resistance being observed in HJURP-overexpressing lines. Recent data from a project under development in the laboratory showed that cells overexpressing HJURP cope better with replicative stress, presenting fewer DNA breaks and greater clonogenic capacity in situations of stress induced by camptothecin. Interestingly, astrocytoma cells treated with camptothecin showed a reduction in HJURP expression levels. Therefore, this project aims to investigate the effects of inducing replication stress on HJURP levels in glioma cells, focusing on aspects that have not yet been clarified, such as the analysis of the kinetics of the observed reduction and cellular mechanisms associated with this reduction.

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