Our scientific proposal aims to clarify the role of small regulatory RNAs in the biology of human cancer. In addition, we work in close collaboration with the University Hospital and the National Cancer Program, providing technological and experimental support for research in Clinical Oncology and the development of new diagnostic biomarkers in cancer.
In recent years, our main focus of research has focused on the study of a new class of molecules generically called small non-coding RNAs. Our work has shown that the fragmentation of these RNAs generates molecules capable of regulating the cell survival pathways to stress and proliferation. We focus primarily on fragments derived from transfer RNAs and Y-RNAs, and their secretion by normal and tumor cells. We study how other cells are capable of capturing and sensing these RNAs released into the extracellular environment, thus representing a new communication mechanism between cells. This and other lines of work of the unit are aimed at identifying new molecular pathways in the initiation and progression of cancer, with special emphasis on new therapeutic targets and diagnostic biomarkers.
Small RNAs derived from tRNA and Y-RNAs as new molecular pathways in cancer and their potential as a source of new diagnostic biomarkers in cancer.
Our main line of research is oriented to the role of new classes of small regulatory RNAs derived from tRNA and Y-RNA as central actors in the proliferation and survival responses to stress, and its potential as new molecular mechanisms in the initiation and progression of cancer. The focus of our current research activities is on the extracellular biology of these regulatory RNAs, and their ability to work as signaling molecules between cells.
Part of our work has shown that these small RNAs are actively secreted by cells through extracellular vesicles or extra-vesicular fractions, being transferred to other cells, constituting a new mechanism of intercellular communication and transfer of genetic information. Additionally, its unique stability in the extracellular environment allows its detection in biological fluids, positioning itself as potential molecular biomarkers in human cancer.
Currently, in collaboration with the Clinical Oncology Service of the Hospital de Clínicas and the National Cancer Institute, we are studying the diagnostic value of small circulating RNAs derived from tRNAGlu, tRNAGly and Y4-RNA in patients with lung cancer.
Research and Development activities with health centers.
Our laboratory is currently participating in a series of initiatives to incorporate new diagnostic biomarkers in oncology, as well as genomic and molecular tools.
Genetic susceptibility to breast cancer. Together with the Hospital de Clínicas of the Faculty of Medicine (Udelar), we have incorporated in the oncology routine the study of mutations of a panel of 11 hereditary predisposition genes to breast and ovarian cancer. This procedure uses next-generation deep sequencing for analysis including the BRCA1 and BRCA2 genes among others.
Biomarkers of therapeutic prediction in lung cancer. Our laboratory performs fluorescent in situ hybridization (FISH) assays to detect translocations of the ALK gene, as a way to predict sensitivity to treatment with inhibitors (Crizotinib) in lung cancer.
International course “Deciphering regulator RNA functions by high-throughput sequencing”. December 4-8, 2017. Organizer: Dr. Cayota. Funded by: UNU-BIOLAC, FOCEM and private sponsors.
2016-2018 – “Implementation of genetic tests for breast cancer risk by deep sequencing of BRCA1 and BRCA2 genes in Uruguayan women”. María Viñas Fund – ANII.
2017-2019 – “Biosensors for the decentralized detection of exosomes and Dengue virus”. Responsible: Juan Pablo Tosar. Funded by: CSIC, University of the Republic.
2017-2019 – “tRNA-derived small RNAs as mediators of survival and growth signals”. Responsible: Alfonso Cayota. Funded by: CSIC, Universidad de la República.
2009-2010 – Member of the Uruguayan team in the Multicenter Pilot Project on Breast Cancer in Latin America with the National Cancer Institute of the United States and its counterparts in Brazil, Argentina, Mexico, Chile and Uruguay. Participants: National Cancer Control Program – Ministry of Public Health; Faculty of Medicine (Udelar), Cancer Research Program of the Institut Pasteur de Montevideo.
2009-2010 – “Helicasas with chromodomain in the initiation and progression of leukemic processes”. Clemente Estable Fund– ANII.
2009-2010 – “MicroRNA-dependent chromohelicases as a novel tumorigenic pathway in human cancer”. Pasteur – Weizmann Joint Research Program.
2008-2010 – “Identification of new molecular mechanisms of human carcinogenesis mediated by micro-RNAs and chromatin remodeling proteins”. Sectorial Commission for Scientific Research (CSIC)
2008-2009 – “miR-181 gene analysis as molecular marker in the initiation and progression of Chronic Lymphoid Leukemia”. Honorary Committee Against Cancer (CHLCC), Uruguay.