Percorrer por autor "Yassuda, Victor"
A mostrar 1 - 3 de 3
Resultados por página
Opções de ordenação
- Pharmacologically targeting tribbles gene expression in colorectal cancerPublication . Yassuda, Victor; Sousa-Coelho, Ana Luísa deTRIB1, TRIB2 and TRIB3 belong to the mammalian Tribbles family of pseudokinases proteins. Several studies reported Tribbles oncogenic role in different types of cancer, including colorectal cancer (CRC).
- Tribbles gene expression profiles in colorectal cancerPublication . Fernandes, Mónica T.; Yassuda, Victor; Bragança, José; Link, Wolfgang; Ferreira, Bibiana; De Sousa-Coelho, Ana LuísaColorectal cancer (CRC) is the third most common cancer and the second leading cause of death due to cancer in the world. Therefore, the identification of novel druggable targets is urgently needed. Tribbles proteins belong to a pseudokinase family, previously recognized in CRC as oncogenes and potential therapeutic targets. Here, we analyzed the expression of TRIB1, TRIB2, and TRIB3 simultaneously in 33 data sets from CRC based on available GEO profiles. We show that all three Tribbles genes are overrepresented in CRC cell lines and primary tumors, though depending on specific features of the CRC samples. Higher expression of TRIB2 in the tumor microenvironment and TRIB3 overexpression in an early stage of CRC development, unveil a potential and unexplored role for these proteins in the context of CRC. Differential Tribbles expression was also explored in diverse cellular experimental conditions where either genetic or pharmacological approaches were used, providing novel hints for future research. This comprehensive bioinformatic analysis provides new insights into Tribbles gene expression and transcript regulation in CRC.
- Uncovering metabolic vulnerabilities and validation of anti-cancer targetsPublication . Yassuda, Victor; Méndez-Lucas, Andrés; Novellasdemunt, Laura; Coelho, Ana Luísa de SousaCancer is a second leading cause of disease-related death worldwide, with one of its defining hallmarks being the tumor metabolism reprograming to sustain growth and survival. While glucose and glutamine have long been recognized as central nutrients, lipid metabolism has recently emerged as a critical element of this metabolic rewiring. Lipids not only provide a dense source of energy but also supply essential building blocks for membrane biosynthesis, thereby supporting proliferation and adaptation. These roles make lipid metabolism an attractive direction for identifying therapeutic vulnerabilities. Based on previous results from our group, we hypothesize that genetic-enzymatic compensations are responsible for reducing the impact of silencing genes associated with lipid metabolism reestablishing the flux. Therefore, our goal was to develop a strategy to double silence oncogene-induced tumor models in vivo via hydrodynamic transfection. As a complementary strategy, we start the develop of colon cancer organoids through sequential CRISPR editing of APC, TP53, KRAS, and SMAD4.So that the same metabolic targets could be extrapolated to other tissues. In parallel, we refined isotopetracing gas chromatography mass spectrometry (GC-MS) protocols to enable highresolution profiling of both polar and apolar metabolites in cellular and organoid system Pilot studies confirmed the feasibility of dual-shRNA constructs and demonstrated reliable induction of MYC expression in vitro, although in vivo tumor formation remains to be optimized. Colon organoids with triple and quadruple edits showed differential tumorigenicity, consistent with literature, while highlighting the need for refined implantation strategies. Importantly, we established robust isotope-tracing GC-MS protocols capable of detecting elongation products beyond C:20 fatty acids and profiling organoid metabolism. Together, these results provide methodological validation and a solid foundation for future studies aimed at uncovering compensatory mechanisms and metabolic vulnerabilities in cancer.