Juan C. Sáez studies the regulation and function of membrane channels (gap junction channels and hemichannels) composed of proteins called connexins or pannexins. The studies are conducted under physiological and pathophysiological conditions using exogenous expression systems or in primary cells of the nervous or immune system. 

During the last decade, he has contributed to understand the involvement of these in the inflammatory response. Since opening of hemichannels is directly involved in the development of inflammatory responses that underlie tissue dysfunction he is searching for potent and selective blockers that could be used as therapeutic agents in diverse chronic diseases with an important inflammatory component. 

1. Sáez J.C., Contreras-Duarte S., Labra V.C., Santibañez C.A., Mellado L.A., Inostroza C.A., Alvear T.F., Retamal M.A., VelardeV., Orellana J.A. Interferon-γ and high glucose-induced opening of Cx43 hemichannels causes endothelial cell dysfunction and damage. Biochem. Biophys. Acta. Molecular Cell Research (in press 2020).
2. Cisterna CB., Vargas A.A., Puebla C., Lagos C.F., Escamilla R., Matus M-F., Vilos C., Cea L.A., Barnafi E., Gaete H., Escobar D.F., Cardozo C., Sáez J.C. Active acetylcholine receptors prevent the atrophy of skeletal muscles and favor reinnervation. Nature Comm. 11: 1073, 2020.
3. Harcha PA., López X, Sáez PJ, Fernández P, Barría I, Sáez JC.  Pannexin-1 channels are essential for mast cell degranulation triggered during Type I hypersensitivity reactions. Frontiers Immunol, 29 November 2019 https://doi.org/10.3389/fimmu.2019.02703.
4. Cea LA, Balboa E, Vargas AA, Puebla C, Brañes MC, Escamilla R, Regueira T, Sáez JC.
   De novo expression of functional connexins 43 and 45 hemichannels increases sarcolemmal permeability of skeletal myofibers during endotoxemia.Biochim Biophys Acta Mol Basis Dis. 2019 Oct 1;1865(10):2765-2773.
5. Sáez JC, Contreras-Duarte S, Gómez GI, Labra VC, Santibañez C.A, Gajardo-Gómez R., Avendaño B.C., Díaz E.F., Montero T.D., Velarde V. Orellana JA. Connexin 43 hemichannel activity promoted by pro-Inflammatory cytokines and high glucose alters endothelial cell function. Front Immunol. 2018 Aug 15;9:1899.
6. Sáez PJ, Vargas,P, Shoji KF, Harcha PA, Lennon-Duménil A-M, Sáez JC. ATP promotes the fast migration of dendritic cells through the activity of pannexin 1 channels and P2X7 receptors. Science Signaling 2017 Nov 21;10(506). pii: eaah7107. doi: 10.1126/scisignal.aah7107. (Recommended in F1000Prime)
7. Maturana CJ, Aguirre A, Sáez JC. High glucocorticoid levels during gestation activate the inflammasome in hippocampal oligodendrocytes of the offspring. Dev Neurobiol. 77(5):625-642 (2017).
8. Cea LA, Puebla C, Cisterna BA, Escamilla R, Vargas AA, Frank M, Martínez-Montero P, Prior C, Molano J, Esteban-Rodríguez I, Pascual I, Gallano P, Lorenzo G, Pian H, Barrio LC, Willecke K, Sáez JC. Fast skeletal myofibers of mdx mouse, model of Duchenne muscular dystrophy, express connexin hemichannels that lead to apoptosis. Cell Mol Life Sci. 73(13): 2583-2599 (2016).
9. Harcha PA, Vargas A, Yi C, Koulakoff AA, Giaume C, Sáez JC. Hemichannels Are Required for Amyloid β-Peptide-Induced Degranulation and Are Activated in Brain Mast Cells of APPswe/PS1dE9 Mice. J Neurosci. 35(25):9526-9538 (2015).
10. Orellana JA, Moraga-Amaro R, Díaz-Galarce R, Rojas S, Maturana CJ, Stehberg J, Sáez JC. Restraint stress increases hemichannel activity in hippocampal glial cells and neurons. Front Cell Neurosci. 2015 Apr 2;9:102. doi: 10.3389/fncel.2015.00102. eCollection 2015.