Profile
Discoveries from recent years have elevated the lysosome from their classical role as a degradative intracellular compartment to a signal integrator and critical regulator of cellular growth, functionality, and survival. In addition to their role in lysosomal storage diseases, several developmental and chronic diseases have been associated with lysosome-related dysfunctions; however, many of the involved mechanisms are unknown. The autophagy-lysosomal system is one of the main catabolic pathways and includes non-selective and selective macroautophagy, microautophagy and chaperone mediated autophagy (CMA). Although about a third of cytoplasmic proteins are degraded by CMA, and this pathway has been implicated in cancer and various metabolic and neurodegenerative diseases; the molecular and regulatory mechanisms of this important pathway of lysosomal protein degradation are still unknown. The main areas of research in our lab involve the molecular characterization and pharmacological modulation of CMA and the elucidation of their role in cancer, neurodegenerative and neurodevelopmental diseases.
- Research Head: Ivan Alfaro
- Post-Doctoral Fellows: Gonzalo Nuñez
- Research Assistants: Rodrigo Alarcon
- Rodrigo Espinosa
- Tamara Rojas
- Juan Hormazabal
- Maria Gallardo
- Liliana Yantén
- Felipe Perez de Arce
National Collaborations
- Dr Mauricio Budini (University of Chile)
- Dr Soledad Matus (Fundación Ciencia & Vida)
- Dra Rebeca Aldunate (Universidad Santo Tomás)
- Dra Alejandra Loyola (Fundacion ciencia & Vida)
Publications
Ormeño F., Hormazabal J., Moreno J., Riquelme F., Rios J., Criollo A., Albornoz A., Alfaro I.E., Budini M. Chaperone Mediated Autophagy Degrades TDP-43 Protein and Is Affected by TDP-43 Aggregation. Front Mol Neurosci. 13:19. doi: 10.3389/fnmol.2020.00019 (2020).
Montoya A., Elgueta D., Campos J., Chovar O., Falcón P., Matus S., Alfaro I., Bono M.R., Pacheco R.J. Dopamine receptor D3 signalling in astrocytes promotes neuroinflammation. Neuroinflammation. 16(1):258. doi: 10.1186/s12974-019-1652-8. (2019).
Acuña RA, Varas-Godoy M, Berthoud VM, Alfaro IE, Retamal MA. Connexin-46 Contained in Extracellular Vesicles Enhance Malignancy Features in Breast Cancer Cells. Biomolecules. 10(5):676. doi: 10.3390/biom10050676. (2019)
Alfaro I.E., Albornoz A., Molina A., Moreno J., Cordero K., Criollo A., Budini M. Chaperone Mediated Autophagy in the Crosstalk of Neurodegenerative Diseases and Metabolic Disorders. Front Endocrinol (Lausanne). 9:778. 2019. doi: 10.3389/fendo.2018.00778 (2018).
Minniti A.N., Arriagada H., Zúñiga S., Bravo‐Zehnder M., Alfaro I.E., Aldunate R. Temporal pattern of neuronal insulin release during Caenorhabditis elegans aging: Role of redox homeostasis. Aging Cell. 18(1):e12855. doi: 10.1111/acel.12855 (2018).
Saavedra F., Rivera C., Rivas E., Merino P., Garrido D., Hernández S., Forné I., Vassias I., Gurard-Levin Z.A., Alfaro I.E., Imhof A., Almouzni G.A., Loyola A. PP32 and SET/TAF-Iβ proteins regulate the acetylation of newly synthesized histone H4. Nucleic Acids Res. 45 (20): 11700-11710. DOI: 10.1093/nar/gkx775 (2017).
Other publications
Saavedra F., Rivera C., Rivas E., Merino P., Garrido D., Hernández S., Forné I., Vassias I., Gurard-Levin Z.A., Alfaro I.E., Imhof A., Almouzni G.A., Loyola A. PP32 and SET/TAF-Iβ proteins regulate the acetylation of newly synthesized histone H4. Nucleic Acids Res. 45 (20): 11700-11710. DOI: 10.1093/nar/gkx775 (2017).
Minniti A.N., Arriagada H., Zúñiga S., Bravo‐Zehnder M., Alfaro I.E., Aldunate R. Temporal pattern of neuronal insulin release during Caenorhabditis elegans aging: Role of redox homeostasis. Aging Cell. 18(1):e12855. doi: 10.1111/acel.12855 (2018).
Alfaro I.E., Albornoz A., Molina A., Moreno J., Cordero K., Criollo A., Budini M. Chaperone Mediated Autophagy in the Crosstalk of Neurodegenerative Diseases and Metabolic Disorders. Front Endocrinol (Lausanne). 9:778. 2019. doi: 10.3389/fendo.2018.00778 (2018).
Acuña RA, Varas-Godoy M, Berthoud VM, Alfaro IE, Retamal MA. Connexin-46 Contained in Extracellular Vesicles Enhance Malignancy Features in Breast Cancer Cells. Biomolecules. 10(5):676. doi: 10.3390/biom10050676. (2019)
Montoya A., Elgueta D., Campos J., Chovar O., Falcón P., Matus S., Alfaro I., Bono M.R., Pacheco R.J. Dopamine receptor D3 signalling in astrocytes promotes neuroinflammation. Neuroinflammation. 16(1):258. doi: 10.1186/s12974-019-1652-8. (2019).
Ormeño F., Hormazabal J., Moreno J., Riquelme F., Rios J., Criollo A., Albornoz A., Alfaro I.E., Budini M. Chaperone Mediated Autophagy Degrades TDP-43 Protein and Is Affected by TDP-43 Aggregation. Front Mol Neurosci. 13:19. doi: 10.3389/fnmol.2020.00019 (2020).