Tumor Immunology and Glycobiology
- Eduardo Osinaga (MD, PhD, Head)
- Nora Berois (MD, PhD, Associate Investigator)
- Edgardo Berriel (MD, MSc, PhD student)
- María Florencia Festari (MSc , PhD student)
- Diego Touyá (MD, MSc, student)
- Claudia Schvartzman (MSc student)
- Cecilia Silva ( MD, MSc, student)
- Guillermo Tramontín (Undergraduate student)
The most abundant form of O-linked glycosylation in higher eukaryotes, termed ‘‘mucin-type’’, is characterized by the covalent linkage of an α-N-acetylgalactosamine residue (GalNAc) to the hydroxyl group of Ser/Thr residues. Mucin core O-glycosylation is catalyzed by a group of UDP-GalNAc: polypeptide N-acetylgalactosaminyl-transferases (ppGalNAc-Ts) (EC. 188.8.131.52). Subsequent elongation of O-linked sugar chains is achieved by the transfer of additional saccharide units, catalyzed by specific glycosyltransferases. Malignant transformation of epithelial cells is commonly associated with changes in the expression level and/or glycosylation pattern of mucins, including exposure of simple mucin-type carbohydrates, such as Tn, sialyl-Tn and TF antigens.
These determinants contribute to the phenotype and biology of cancer cells and are involved in their metastatic activity. Moreover, they are considered among the most specific cancer-associated structures, and are thus being evaluated as promising targets for tumor immunotherapy. We have recently identified some apomucins and glycosyltransferases, which are abnormally expressed in certain cancer cells. One of these enzymes, ppGalNAc-T13, is probably associated to the aggressiveness of some tumors. We investigate the molecular mechanisms underlying the regulation of the initial steps of mucin-type O-glycosylation in human cancer, and evaluate how this abnormal process influences malignant cell behavior.
The Tumor Immunology and Glycobiology Laboratory research is focused on:
- How abnormal regulation of the initial steps of mucin-type O-glycosylation in human cancer could influence malignant cell behavior. We evaluate whether the expression of GalNAc-Ts could modify cancer cell properties in vitro (susceptibility to apoptosis, clonogenicity, invasiveness, chemoresistance, etc.) and in vivo (tumor growth, metastasis). We intensify our research on the characterization of GalNAc-T isoenzymes as new tumor markers.
- Characterization of parasite glycoproteins which induce anti-cancer immunity. We focus on the identification, purification and characterization of these molecules from T. cruzi and E. granulosus. Therapeutic experiments are performed with different fractions (enriched and depleted in specific carbohydrates).
- Producción por ingeniería genética de diabodies e inmunotoxinas anti-antígeno tumoral Tn. Aplicación en imagenología molecular y tratamiento del cáncer. ANII – Fondo María Viñas. U$S 47.000, 2013-2015
- Grupo de Inmunología Tumoral. Proyecto Grupo I+D CSIC-UdelaR. U$S 100.000, 2011-2015.
- Berois N, Heard I, Fort Z, Alonso R, Sica A, Moerzinger P, Rodriguez G, Sancho-Garnier H, Osinaga E, Favre M. Prevalence of type-specific HPV infection in Uruguay (2014) Journal of Medical Virology, 86 (4), pp. 647-652. – IF: 2.217
- Berois N, Osinaga E. Glycobiology of neuroblastoma: Impact on tumor behavior, prognosis, and therapeutic strategies (2014) Frontiers in Oncology, 4 MAY, art. no. 114. – IF: —
- Libisch MG, Casás M, Chiribao M, Moreno P, Cayota A, Osinaga E, Oppezzo P, Robello C. GALNT11 as a new molecular marker in chronic lymphocytic leukemia. Gene. 2014 Jan 1;533(1):270-9. doi: 10.1016/j.gene.2013.09.052.
- Ikemori R, Longo Machado C, Furuzawa K, Nonogaki S, Osinaga E, Umezawa K, Carvalho MA, Verinaud L and Chammas R. Galectin-3 up-regulation in hypoxic and nutrient deprived microenvironments promotes cell survival. Plos One (2014). – IF: 3.534.