Bioquímico, ETH, Zürich, Switzerland.
Doctor en Ciencias Naturales, ETH, Zürich, Suiza.
Profesor Titular, Facultad de Medicina, Universidad de Chile
Laboratorio de Comunicaciones Celulares
Área de investigación: Bioquímica y Biología Celular, Microbiología
Línea(s) de Investigación: (posibles tesis)
Rol de Caveolina-1 exosomal en promover angiogénesis y metástasis de tumores
Rol de Helicobacter pylori en cáncer gastrica y efectos sistemicos de la bacteria inducidas por la liberación de OMVs
Líneas de Investigación
Role of caveolin-1 in exosomes. CAV1 is also known to be present in exosomes from breast cancer and melanoma cells; however, its role there remains poorly defined. We have evidence that aggressive breast cancer cells, which express endogenously CAV1 produce exosomes with CAV1. Moreover, these CAV1 containing exosomes, but not exosomes from CAV1 knock-down cells, promote migration, invasion and metastasis of less aggressive recipient breast cancer cells. By mass spectrometry analysis, we identified a number of proteins that are exclusively present in CAV1 containing exosomes as related functionally to the process of cell adhesion. Currently, studies evaluating the role of these proteins in the biological responses triggered by CAV1 exosomes are underway.
Helicobacter pylori related work. The development of gastric cancer associated with Helicobacter pylori (H. pylori) infection has been linked to oxidative stress generated in part due to an immune response against bacterial virulence factors. H. pylori gamma glutamyl transpeptidase (GGT) is a secreted enzyme that contributes to production of reactive oxygen species and is associated with peptic ulcer development. Alternatively, although expression of the inhibitor-of-apoptosis protein survivin in adults is frequently linked to the development of cancer, evidence indicating that the protein is present in normal gastric mucosa is also available. Our results revealed that H. Pylori infection of gastric cells leads to loss of survivin and cell death via a mechanism mediated by GGT. Alternatively, we have more recently become interested in how H. Pylori infection induces the expression of hypoxia-induced factor-1a, a transcription factor that coordinates many aspects important to tumor development. Most recent results implicate the virulence factor urease in this process by acting as a ligand that binds to the toll-like receptor-2 (TLR2). Currently, we are evaluating how these events contribute to inflammation induced by H. Pylori, as well as how H. pylori may trigger extragastric effects via the release of Outer Membrane Vesicles (OMVs). Together, we anticipate our observations will open up the possibility of developing effective non-invasive tools for early diagnosis and treatment of early stage disease using nanotechnology.
Arrua, E.C., Sanchez, S., Trincado, V., Hidalgo, A., Quest, A.F.G., Morales, J.O. “Experimental design and optimization of a novel dual-release drug delivery system with therapeutic potential against infection by Helicobacter pylori. Colloids and Surfaces B: Biointerfaces”. European Journal of Pharmaceutics and Biopharmaceutics May 2022, 213, 112403. ISI 5,571 (Q1).
Soto, C., Rojas, V., Yáñez, L., Olivera, M., Pacheco, M., Venegas, D., Salinas, D., Bravo, D., Quest, A.F.G. “Porphyromonas gingivalis–Helicobacter pylori coincubation enhances Porphyromonas gingivalis virulence and increases migration of infected human oral keratinocytes” J. Oral Microbiol. 2022, 14(1): 2107691.
Published online 2022 Aug 12. doi: 10.1080/20002297.2022.2107691 ISI 5.833 (Q1).
Díaz-Valdivia, N., Simon, L., Diaz, J., Martinez-Meza, S., Contreras, P., Burgos-Ravanal, R., Perez, V.I., Frei, B., Leyton, L., Quest, A.F.G. “Mitochondrial dysfunction and the glycolytic switch induced by caveolin-1 phosphorylation promotes cancer cell migration, invasion and metastasis” Cancers 2022 Jun 10;14(12):2862.doi: 10.3390/ cancers14122862. ISI 6.639 (Q1).
Castro, I., Carvajal, P., Heathcotem, B., Aguilera, S., Jara, D., Barrera, M-J., Aliaga-Tobar., V., Maracaja-Coutinho, V., Urzua, U., Quest, A.F.G., González, S., Molina, C., Hermoso, M., and González, M.J. “Small RNA expression profiling reveals hsa-miR-181d-5p downregulation associated with TNF-α overexpression in Sjögren’s syndrome patients.” Frontiers in Immunology, section Autoimmune and Autoinflammatory disorders Apr 1;13:870094. doi: 10.3389/fimmu.2022.870094. eCollection 2022. ISI 7.561 (Q1).
Simon, L., Sanhueza, S., Gaete, M.B.,Varas, M., Quest, A.F.G. “Role of the pro-inflammatory tumor microenvironment in extracellular vesicle-mediated transfer of therapy resistance” Frontiers in Oncology, Cancer Molecular Targets and Therapeutics Section, 11 May 2022, https://doi.org/10.3389/fonc.2022.897205. ISI 6.244 (Q1).
Pérez, L.A., León ,J,. López, J., Rojas, D., Reyes, M., Contreras, P., Quest, A.F.G., Escudero, C., Leyton, L.. “The GPI-Anchored Protein Thy-1/CD90 Promotes Wound Healing upon Injury to the Skin by Enhancing Skin Perfusion” Int J Mol Sci. 2022 Oct 19;23(20):12539. doi: 10.3390/ijms232012539 ISI 6.208 (Q1).
Gonzalez, M.F., Burgos-Ravanal, R., Shao, B., Heinecke, J., Valenzuela-Valderama, M., Corvalan, A.H., Quest, A.F.G. “Extracellular vesicles from gastric epithelial GES-1 cells infected with Helicobacter pylori promote changes in recipient cells associated with malignancy” Front. Oncol. 2022. Sec. Molecular and Cellular Oncology doi: 10.3389/fonc.2022.962920. ISI 6.244 (Q1).
Díaz-Vesga, M.C., Flores-Vergara, R., Riquelme, J.A., Vergara, C., Donoso, P., Llancaqueo, M., Michea, L., Quest, A.F.G., Olmedo, I., and Pedrozo, Z. “Polycystin-1 is a crucial regulator of BIN1 expression and T-tubule remodeling associated with the development of dilated cardiac myopathies” Int J Mol Sci. (2022) 24(1), 667; https://doi.org/10.3390/ijms24010667. ISI 6.208 (Q1).Sanhueza, S., Simon, L., Cifuentes, M., Quest, A.F.G. “The adipocyte-macrophage relationship in cancer: a potential target for antioxidant therapy” Antioxidants 2023, 12, 126. https://doi.org/10.3390/antiox12010126. ISI 7.675 (Q1), top ten.
Pérez-Nuñez, R., Chamorro, A., Gonzalez, M.F., Contreras, P., Artigas, R., Corvalán, A.H., van Zundert, B., Reyes, C., Moya, P.R., Avalos, A.M., Schneider, P., Quest, A.F.G., Leyton, L. “Protein Kinase B (AKT) upregulation and Thy-1-αvβ3 integrin-induced phosphorylation of Connexin43 by activated AKT in astrogliosis” J. Neuroinflammation 2023 Jan 6;20 (1):5. ISI 9.587 (Q1), top ten
Palacios, E., Lobos-González, L., Guerrero, S., Kogan, M., Heinecke, J., Quest, A.F.G., Leyton, L.,* and Valenzuela, M. “Helicobacter pylori outer membrane vesicles induce astrocyte reactivity through NF-κB activation and cause neuronal damage in vivo in a murine model” J. Neuroinflammation 2023 Mar 9;20(1):66.
doi: 10.1186/s12974-023-02728-7. ISI 9.587 (Q1), top ten