Full professor Department of Physiological Sciences, Pontificia Universidad Católica de Chile, Santiago-Chile.
Director of the Ph.D. program in Physiological Sciences, Pontificia Universidad Católica de Chile, Santiago-Chile.
Director Subrogante del Centro Interdisciplinario de Neurociencia de Valparaíso
Biochemist, Universidad de Concepción, Chile Ph.D. en Ciencias, mención Neurociencias, Albert Einstein College of Medicine of Yeshiva University, Nueva York, E.E.U.U.
Regulation and function of connexin and pannexin based membrane channels. In collaboration with students (undergraduate and graduate), Chilean and international researchers, we study the regulation and functional roles of plasma membrane channels formed by connexins (Cxs) or pannexins (Panxs), which are proteins expressed by most cell types in vertebrates. They constitute channels termed gap junction channels (GJCs) and hemichannels (HCs) or connexons. GJCs communicate the cytoplasm of contacting cells and HCs communicate the intra and extra cellular compartments. We also study the interactions of Cx and Panx based channels with purinergic receptors (P2). All these channels are crucial in the coordination of numerous cellular responses in diverse tissues. Our studies focus mainly in normal and aberrant functioning of the nervous and immune systems. We use primary cultures, cell lines and animal models of inflammatory diseases or diseases that evolve with an inflammatory response. We analyze the effects of neurotransmitters, hormones and pro-inflammatory conditions on the extent of intercellular communication and cell death mediated by the channels of interest. Biochemical, biophysical, cellular and molecular biological techniques are used to study the expression, post-transcriptional modifications and intercellular trafficking of Cxs and Panxs. In collaboration with industries (R+D), we are currently developing chemical compounds that affect these channels to control the deleterious consequences of pro-inflammatory conditions. Since regeneration is the last step of inflammatory responses and shares numerous features with tissue ontogeny, we also perform research on the regulation and function of the channels of interest in cell growth and differentiation. The final goal of the latter is to gain knowledge on the role of GJCs and HCs in tumorogenesis.
Selected publications :
- Schalper, K.A., Palacios-Prado, N., Retamal, M.A., Shoji, K.F., Martínez A.D. and Sáez. J.C. The connexin hemichannel composition determines the FGF-1-induced membrane permeability and free ?Ca2+?i responses. Mol. Biol. Cell. 19: 3501–3513 (2008).
- Eugenín, E.A., M.C. Brañes, J.W. Berman & J.C. Sáez. 2003. TNF-alpha plus IFN-gamma induce connexin43 expression and formation of gap junctions between human monocytes/macrophages that enhance physiological responses. J. Immunol. 170 (3): 1320-1328.
- Sáez, J.C., V.M. Berthoud, M.C. Brañes, A.D. Martínez & E.C. Beyer. 2003. Plasma membrena channels formed by connexins: Their regulation, and function. Physiol. Rev. 83: 1359-1400.
- Contreras, J.E., H.A. Sanchez, E.A. Eugenín, D. Speidel, M. Theis, K. Willecke, F.F. Bukauskas, M.V. Bennett & J.C. Sáez. 2002. Metabolic inhibition induces opening of unapposed connexin 43 gap junction hemichannels and reduces gap junctional communication in cortical astrocytes in culture. Proc. Natl. Acad. Sci. U S A. 99: 495-500.
- Sáez, J.C., J.A. Connor, D.C. Spray & M.V.L. Bennett. 1989. Hepatocyte gap junctions are permeable to the second messengers inositol 1,4,5-trisphosphate and calcium ions. Proc. Natl. Acad. Sci. USA 86: 2708-2712.
- Sáez, J.C., D.C. Spray, A.C. Nairn, E.L. Hertzberg, P. Greengard & M.V.L. Bennet. 1986. cAMP increases junctional conductance and stimulates phosphorylation of the 27kDa principal gap junction polypeptide. Proc. Natl. Acad. Sci. USA 83: 2473-2477.