El ISPA acogerá el viernes 24 de noviembre la conferencia Targeting tRNA methyltransferases in cancer, de la Dra. Sandra Blanco Benavente, Científica Titular del CSIC del Centro de Investigacion del Cáncer – CSIC – Universidad de Salamanca, IBSAL.
La charla tendrá lugar en la sala N-1 S2 006 del HUCA a partir de las 12:00 h.
Reseña biográfica de la conferenciante
The IP’s research has focused since her postdoc in deciphering the role of RNA modifications (epitranscriptome) in stem cell biology, homeostasis and disease. Throughout her training at the Stem Cell Institute, Cambridge University, CIC-bioGUNE and CIC, she became expert in stem cell biology, pre-clinical models, epitranscriptomics, cancer, immunology, the development of novel tools to determine RNA modifications genome-wide. In October 2018, she joined the Cancer Research Centre (Salamanca) as CSIC Scientist (Científico Titular). Since then, she leads the “Epitranscriptomics and Cancer Lab” at CIC-CISC-USAL. In 2021, she became an Associate Researcher at IBSAL (Salamanca). In 2023 she became director of the Cosolidated Research Unit UIC 258 in Castilla y León (Spain). Her research has been pioneer demonstrating how the epitranscriptome, in particular methylation of tRNAs, regulate essential functions for stem cell maintenance and differentiation, migration and survival to stress in humans and mice. Her research has also established that mutations or aberrant expression of the writers of tRNAs can lead to neurodevelopment diseases and cancer. Her findings have established that manipulation (inhibition) of the enzymes that regulate tRNA modifications is a potent and promising strategy to eliminate cancer stem cells or to modulate the tumour immune microenvironment.
Temática de la charla
Non-mutational events, particularly RNA post-transcriptional modifications, are emerging as key players in tumour development and progression in several cancer types. Emerging evidence show that self-renewal, survival and migration are regulated by epitranscriptomic marks, which may be a potential therapeutic target to specifically eliminate cancer cells. By using genomic screenings, epitranscriptomic tools, CRISPR/Cas9 technology, proteomics, cell and mouse models and patient samples we aim to decipher the epitranscriptome in prostate cancer in order to implement novel therapeutic strategies. We found that overexpression of novel transfer RNA (tRNA) methyltransferases correlated with poor prostate cancer prognosis. Loss-of-function analyses resulted in reduced protein synthesis, cell proliferation, and tumour formation in vivo. Mechanistically reduced tRNA methylation resulted in reduced global protein synthesis, but increased expression of metabolic and secretion pathways regulators, resulting in increased infiltration of pro-inflammatory immune cells in tumours. In summary, we find that tRNA modifications regulate cell proliferation, metabolic pathways and the tumour microenvironment crosstalk by adapting the translational machinery. Targeting tRNA methylation is emerging as an effective therapeutic tool to eliminate cancer cells. Whether targeting tRNA methylation alone, or in combination with agents targeting metabolic pathways or immunotherapy can be used as effective therapeutic tools needs further validation.
