Profile
In response to diverse stress stimuli, including nutrient restriction, infections or proteotoxicity, eukaryotic cells activate a common adaptive pathway, termed the integrated stress response (ISR), to restore cellular homeostasis. The core event in this pathway is the phosphorylation of the eukaryotic translation initiation factor 2 alpha (eIF2a) by one of four members of the eIF2a kinase family, which leads to a decrease in global protein synthesis and also the induction of selected genes that together promote cellular recovery. We are focused on understanding the contribution of this signaling pathway to neurodegenerative process and aging. Using in vivo and in vitro models, we study the consequences of targeting ISR components to open new therapeutic strategies for treating neurodegenerative diseases.
- Research Head: Soledad Matus Montero
- Undergraduate Students: Felipe Gómez Ibarra, Juan Francisco Roa, Ignacio Silva Pizarro, Alejandra Trujillo Espergel
- Research Assistants: Pamela Farfán González, Biochemist
- Ph D Students: Marcela Escandón Bernal
- Post-doctoral Fellows: Nicolás Martinez Alarcón
- Paulina Falcón Urrutia, Post-doctoral Fellow
- Luis Osorio. PhD Student. Universidad de Chile.
- Alvaro Brito Arratia, Undergraduate Student.
- Carolina Jerez. Biochemist. Research Assistant.
- Yamil Marambio. Biochemist. Research Assistant.
- Natalia Muñoz. Chemistry Analyst. Research Assistant.
National Collaborations:
• Dr. Claudio Hetz. Universidad de Chile.
• Dr. Felipe Court. Universidad Mayor.
• Dr. Rene Vidal. Universidad Mayor.
• Dr. Patricio Olguín (Faculty of Medicine, Universidad de Chile).
International Collaborations:
• Dr. Mauro Costa-Mattioli. Baylor University.
• Dr. Lionel Muller Igaz. Universidad de Buenos Aires
• Dr. Francisco Herrera. Trancura Biosciences.
Publications
Matus S, Burgos PV, Bravo-Zehnder M, Kraft R, Porras OH, Farías P, Barros LF, Torrealba F, Massardo L, Jacobelli S, González A. (2007). Antiribosomal-P autoantibodies from psychiatric lupus target a novel neuronal surface protein causing calcium influx and apoptosis. J Exp Med. 2007 Dec 24;204(13):3221-34.
Matus S., Lisbona F., Torres M., Leon C., Thielen P., and Hetz C. (2008). The stress rheostat: Interplay between the Unfolded Protein Response (UPR) and Autophagy in neurodegeneration. Curr. Mol. Med. 8:157-172. #
Hetz C, Thielen P, Matus S., M Nassif, Court F., Cuervo AM., Martinez G., Kiffin R., R.H. Brown and Glimcher L. (2009). “XBP-1 deficiency in the nervous system protects against amyotrophic lateral sclerosis by increasing autophagy”. Genes & Dev. 23:2294–2306. (Cover illustration) *Commented in Genes Dev. (2009), 23:2294-306.
Matus S., Nassif M., Glimcher LH, and Hetz C. (2009).“XBP-1 deficiency in the nervous system revealed a homeostatic switch to activate autophagy”. Autophagy. Nov 6;5(8). (Cover illustration).
Nassif M, Matus S, Castillo K, and Hetz C. (2010).“Amyotrophic lateral sclerosis pathogenesis: a journey through the secretory pathway”. Antiox Red. Sig, 13:1955-89.
Matus S., Glimcher LH., and Hetz C. (2011).“Protein folding stress in neurodegenerative diseases: a glimpse into the ER”. Curr Op. Cell Biol. 23:239-52.
Gupta S, Read DE, Deepti A, Cawley K, Gupta A, Oommen D, Verfaillie T, Matus S, Smith MA, Mott JL, Agostinis P, Hetz C, Samali A. (2012). “Perk-dependent repression of miR-106b-25 cluster is required for ER stress-induced apoptosis”. Cell Death Dis. 2012 Jun 28;3:e333.
Matus S, Castillo K, Hetz C. (2012). “Hormesis: protecting neurons against cellular stress in Parkinson disease”. Autophagy. Jun;8(6):997-1001.
Castillo K, Nassif M, Valenzuela V, Rojas F, Matus S, Mercado G, Court F, van Zundert B, and Hetz C. (2013). “Trehalose delays the progression of amyotrophic lateral sclerosis by enhancing autophagy in motoneurons”. Autophagy. 2013 Jun 6;9(9).
Castillo K, Valenzuela V, Nassif M, Oñate M, Encina G, Matus S, Irrazabal T, Parsons G, Court F, Schneider B, Aebischer P, Armentano D and Hetz C. (2013)“Measurement of autophagy flux in the nervous system in vivo”. Cell Death and Differentiation. 2013; 4:e917.
Matus S, Lopez E, Valenzuela V, Nassif M and Hetz C. (2013). “Functional role of the transcription factor ATF4 in the pathogenesis of amyotrophic lateral sclerosis”. PLoS One. 2013 Jul 18;8(7):e66672.
Matus S., Valenzuela V, Medinas D, Hetz, C. (2013).“New insights about the role of ER stress in ALS”. Int J Cell Biol. 2013:674751. Review
Matus S., Valenzuela V., Hetz, C. (2014). “A new method to measure of autophagy flux in the nervous system”. Autophagy. 2014 10(4):710-714.
Nassif M., Valenzuela V., Rojas-Rivera D., Vidal R., Matus S., Castillo K., Fuentealba Y., Kroemer G., Levine B. and Hetz C. (2014) “Pathogenic role of Beclin 1/BECN1 in the development of amyotrophic lateral sclerosis” Autophagy. 2014 10:7,1-16.
Matus S. Medina D and Hetz C. (2014) “Common Ground: Stem Cell Approaches Find Shared Pathways Underlying ALS”. Cell Stem Cell. 2014. 14: 697-699.
Matus S, Bosco DA, Hetz C. 2014“Autophagy meets fused in sarcoma-positive stress granules”. Neurobiology of Aging. 2014 12: 2832-5.
Vidal R., Matus S., Bargsted L. and Hetz C. (2014).“Targeting Autophagy in Neurodegenerative Diseases” TiPS, 2014. 35. 11: p583–591.
Woehlbier U., Colombo A., Saaranen M.J., Pérez V., Ojeda J., Bustos F.J., Andreu C.I,. Torres M., Valenzuela V., Medinas D.B., Rozas P., Vidal R.L., Lopez-Gonzalez R., Salameh J., Fernandez-Collemann S., Muñoz N., Matus S., Armisen R., Sagredo A., Palma K., Irrazabal T., Almeida S., Gonzalez-Perez P., Campero M., Gao F.B., Henny P., van Zundert B., Ruddock L.W., Concha M.L. Henriquez J.P., Brown R.H., Hetz C. “ALS-linked protein disulfide isomerase variants cause motor dysfunction”. (2015). EMBO J. 2016 Apr 15;35(8):845-65.
Klionsky D.J., et al.“Guidelines for the use and interpretation of assays for monitoring autophagy” 3rd (edition). Autophagy. 2016;12(1):1-222.
Bargsted L., Hetz C., Matus S. “ERp57 in neurodegeneration and regeneration”. Neural Regen Res. (2016) Feb;11(2):232-3. |
Garcia-Huerta P., Bargsted L., Rivas A., Matus S., Vidal R. “ER chaperones in neurodegenerative disease: Folding and beyond”. Brain Res. (2016) Oct 1; 1648(Pt B):580-587
Bargsted L, Medinas DB, Martínez Traub F, Rozas P, Muñoz N, Nassif M, Jerez C, Catenaccio A, Court FA, Hetz C, Matus S. Disulfide cross-linked multimers of TDP-43 and spinal motoneuron loss in a TDP-43A315T ALS/FTD mouse model. Sci Rep. (2017) 7(1):14266. doi: 10.1038/s41598-017-14399-5. | PDF
Matamala JM, Arias-Carrasco R, Sanchez C, Uhrig M, Bargsted L, Matus S, Maracaja-Coutinho V, Abarzua S, van Zundert B, Verdugo R, Manque P, Hetz C. Genome-wide circulating microRNA expression profiling reveals potential biomarkers for amyotrophic lateral sclerosis. Neurobiol Aging. (2018) 64:123-138. doi: 10.1016/j.neurobiolaging.2017.12.020. | PDF
Montoya A, Elgueta D, Campos J, Chovar O, Falcón P, Matus S, Alfaro I, Bono MR, Pacheco R.JDopamine receptor D3 signalling in astrocytes promotes neuroinflammation. Neuroinflammation. (2019) 16(1):258. doi: 10.1186/s12974-019-1652-8. | PDF
Beltran S, Nassif M, Vicencio E, Arcos J, Labrador L, Cortes BI, Cortez C, Bergmann CA, Espinoza S, Hernandez MF, Matamala JM, Bargsted L, Matus S, Rojas-Rivera D, Bertrand MJM, Medinas DB, Hetz C, Manque PA, Woehlbier U. Network approach identifies Pacer as an autophagy protein involved in ALS pathogenesis. Mol Neurodegener. (2019) 14(1):14. doi.org/10.1186/s13024-019-0313-9 | PDF
Falcón P, Escandón M, Brito Á, Matus S. Nutrient Sensing and Redox Balance: GCN2 as a New Integrator in Aging. Oxid Med Cell Longev. (2019) May 22;2019:5730532. doi: 10.1155/2019/5730532. | PDF
Barrera MJ, Aguilera S, Castro I, Matus S, Carvajal P, Molina C, González S, Jara D, Hermoso M, and María Julieta González. “Tofacitinib counteracts IL-6 overexpression induced by deficient autophagy: implications in Sjögren’s syndrome”. Rheumatology. (2020) 1–12. DOI: 10.1093/rheumatology/keaa670.
“Enforced dimerization between XBP1s and ATF6f enhances the protective effects of the UPR in models of neurodegeneration” Mol Ther. (2021) Feb 3; S1525-0016(21)00067-8. DOI: 10.1016/j.ymthe.2021.01.033.
Martínez NW, FE Gomez, and Matus S. “The potential role of Protein Kinase R as a regulator of age-related neurodegeneration” Front. Aging Neurosci. (2021) Accepted Manuscript. DOI: 10.3389/fnagi.2021.638208
Principal investigator
María Soledad Matus Montero, PhD
+56 22 367 2012
smatus@cienciavida.org
Biography