Physiology and Pharmacology : Guillermo Vazquez

Assistant Professor Phone: (419) 383-5301 Fax: (419) 383-2871 E-mail: Guillermo.Vazquez@utoledo.edu

Training: 

• B.Sc., Biochemistry, 1990, Universidad Nacional del Sur, Bahia Blanca, Argentina
• Ph.D., Biochemistry, 1997, Universidad Nacional del Sur, Bahia Blanca, Argentina

Appointments:

• Member of the Scientific and Technological Researcher Career, CONICET, Argentina, 1997-2004
• Visiting Postdoctoral Fellow, Calcium Regulation Group, Laboratory of Signal Transduction, National Institute of  Environmental Health Sciences, North Carolina, 2001-2005
• Research Fellow, Calcium Regulation Group, Laboratory of Signal Transduction, National Institute of  Environmental Health Sciences, North Carolina, 2006-2007
• Assistant Professor, Department of Physiology and Pharmacology, University of Toledo College of Medicine, Health Science Campus, Toledo, Ohio, February 2007-

Research Interests:

Understanding the role of calcium signaling in endothelial dysfunction and endothelial response to vascular inflammation associated to cardiovascular, metabolic and endocrine-related diseases.

Research: 

Endothelial cells play a crucial role in the pathogenesis of the vascular inflammation associated to several cardiovascular, metabolic and endocrine-related diseases, such as atherosclerosis, type-2 diabetes and obesity. The early stages of vascular inflammation are characterized by a dynamic interaction between endothelial cell dysfunction and the response of the endothelial cell to proinflammatory signals, involving a complex signaling scenario that includes impaired generation of nitric oxide, increased expression of cell adhesion molecules and induction of inflammatory pathways, among others. Whereas the importance of calcium (Ca2+) signaling, particularly Ca2+ entry through plasma membrane resident Ca2+ channels, in endothelial cell physiology and pathophysiology has received increased appreciation over the last decade, our understanding of the precise role of Ca2+ entry within the signaling events underlying endothelial cell dysfunction is in its infancy, despite the fact that several of those signaling events are, directly or indirectly, Ca2+-dependent. Canonical Transient Receptor Potential (TRPC) channels, which belong to the larger superfamily of mammalian TRP channel forming proteins, are among the most important Ca2+-permeable cation channels in vascular endothelium. Mammalian TRPC proteins (TRPC1 through TRPC7) form channels typically activated downstream receptor-dependent stimulation of phosphoinositide-specific phospholipase C (PLC), a common step in the signaling of G protein-coupled receptors and receptor tyrosine kinases. Indeed, TRPC proteins form, or are part of, the channels that take part in the action of various PLC-coupled receptors for transmitters, peptides and growth factors that modulate diverse vascular functions, such as regulation of vascular tone and permeability, secretion, endothelial cell proliferation and apoptosis. Current work in Dr. Vazquez’s laboratory is primarily on two aspects of endothelial Ca2+ signaling: 

• identifying the TRPC proteins that build up receptor-regulated Ca2+ permeable channels in vascular endothelial cells as well as characterizing the receptor-associated signaling fundamental to regulation of  channel activity;

  the signaling consequences of TRPC-mediated Ca2+ entry within the context of endothelial dysfunction and endothelial response in vascular inflammation, such as their role in Ca2+-dependent regulation of cell adhesion molecule expression, inflammatory signaling (i.e., calcineurin/NFAT) and nitric oxide production.

The laboratory makes use of cell models of endothelial dysfunction/inflammation, and a number of techniques including, among others, patch clamp electrophysiology, confocal- and camera-based fluorescence imaging, protein chemistry/molecular biology, antisense and siRNA technology.

Selected Publications:

• Vazquez G, de Boland AR, Boland R. 2000. Involvement of calmodulin in the 1,25dihydroxivitaminD3-induced SOC influx in skeletal muscle cells. J. Biol. Chem., 275, 16134-16138.
• Capiati D, Vazquez G, Tellez-Iñon MT, Boland R. 2000. Role of PKC in 1,25(OH)2-vitamin D3 regulation of intracellular calcium levels during development of sekeletal muscle cells in culture. J. Cell. Biochem., 77, 200-212.
• Santillán G, Vazquez G, Boland R. 1999. Activation of a beta-adrenergic-sensitive signal transduction pathway by the secosteroid hormone 1,25-dihydroxy-vitamin D3 in chick heart. J. Mol. Cell. Cardiol., 31, 1095-1104.
• Vazquez G, Sellés J, Boland AR, Boland R. 1999. Rapid actions of calcitriol and its side-chain analogues CB1093 and GS1500 on intracellular calcium levels in skeletal muscle cells: a comparative study. Br. J. Pharmacol., 126, 1815-1823.
• Vazquez G, de Boland AR, Boland R. 1998. 1,25-dihydroxy-vitamin D3 - induced store-operated Ca2+ influx in skeletal muscle cells requires activation of phospholipase C and is modulated by PKC and tyrosine kinases. J. Bio. Chem., 273, 33954-33960.
• Vazquez G, Lievremont JP, Bird GSJ, Putney J W. Jr.  2001. Human Trp3 forms both inositol trisphosphate receptor-dependent and receptor-independent store-operated cation channels in DT40 avian B lymphocytes. Proc. Natl. Acad. Sci. USA, 98, 11777-11782.
• Vazquez G, Wedel B, Bird GSJ, Joseph S, Putney J W.Jr. 2002. An Inositol 1,4,5-trisphosphate Receptor-dependent Cation Entry Pathway in DT40 B Lymphocytes. EMBO Journal, 21, 4531-4538.
• Baldi C, Vazquez G, Boland R. 2002. Characterization of a 1,25(OH)2D3-responsive capacitative calcium entry pathway in rat osteoblastic like cells. J. Cell.Biochem., 86, 678-687.
• Baldi C, Vazquez G, Boland R. 2003. Capacitative calcium influx in human epithelial breast cancer and non-tumorigenic cells occurs through Ca2+ entry pathways with different permeabilities to divalent cations. J. Cell. Biochem., 88, 1265-1272.
• Vazquez G, Wedel B, Trebak M, Bird GSJ, Putney JW Jr. 2003. Expression Level of TRPC3 Channel Determines Its Mechanism of Activation. J. Biol. Chem., 278, 21649-21654.
• Trebak M, Vazquez G, Bird GSJ, Putney J W. Jr. 2003. The TRPC3/6/7 subfamily of cation channels. Cell Calcium, 33, 451-461.
• Wedel B, Vazquez G, McKay R, Bird GSJ, Putney J W. Jr. 2003. A Calmodulin/IP3 receptor binding region targets TRPC3 to the plasma membrane in a calmodulin/IP3 receptor-independent process. J. Biol. Chem., 278, 25758-25765.
• Baldi C, Vazquez G, Calvo J, Boland R. 2003. TRPC3-like Protein is involved in the Capacitative Cation Entry induced by 1a,25-dihydroxy-vitamin D3 in ROS 17/2.8 Osteoblastic Cells. J. Cell. Biochem., 90, 197-205.
• Putney JW Jr., Trebak M, Vazquez G, Wedel B, Bird GSJ. 2004. Signaling Mechanisms for TRPC3 Channels. Nov. Found. Symp., 258, 123-133.
• Bird GSJ, Wedel B, Lievremont JP, Trebak M, Aziz O, Vazquez G, Putney JW Jr. 2004. Mechanisms of Phospholipase C-Regulated Calcium Entry. Cur. Mol. Med., 4, 291-301.
• Santillan G, Katz S, Vazquez G, Boland R. 2004. TRPC3-like protein and vitamin D receptor mediate 1a,25(OH)2-Vitamin D3-induced SOC influx in muscle cells. Int. J. Biochem. Cell Biol., 36, 1910-1918.
• Santillan G, Baldi C, Katz S, Vazquez G, Boland R. 2004. Evidence that TRPC3 is a  molecular component of the 1a,25(OH)2-Vitamin D3-activated capacitative calcium entry (CCE) in muscle and osteoblast cells. J. Ster. Biochem. Mol. Biol., 89-90, 291-295.
• Vazquez G, Wedel B, Kawasaki B, Bird GSJ, Putney JW Jr. 2004. Obligatory role of Src kinase in the signaling mechanism for TRPC3 cation channels. J. Biol. Chem., 279, 40521-40528.
• Vazquez G, Wedel B, Aziz O, Trebak M, Putney JW Jr. 2004. The mammalian TRPC cation channels. Biochim. Biophys. Acta, 1742, 21-36
• Lievremont JP, Numaga T, Vazquez G, Lemonnier L, Hara Y, Mori E, Trebak M, Moss S, Bird GSJ, Mori Y, Putney JW Jr. 2005. The role of Canonical Transient Receptor Potential 7 (TRPC7) in B-cell receptor-activated channels. J. Biol. Chem., 279, 40521-40528.
• Vazquez G, Bird GSJ, Mori Y, Putney JW Jr. 2006. Native Canonical Transient Receptor Potential 7 channel activation by an inositol trisphosphate receptor-dependent mechanism. J. Biol. Chem., 281, 25250-25258.
• Smyth TS, Lemonnier L, Vazquez G, Bird GSJ, Putney JW Jr. 2006. Dissociation of regulated trafficking of TRPC3 channels to the plasma membrane from their activation by phospholipase C. J. Biol. Chem., 281, 11712-11720.
• Vazquez G, Putney JW Jr. 2006. Role of Canonical Transient Receptor Potential Channels (TRPC) in Receptor-Dependent Regulation of Vascular Cell Adhesion Molecule-1 In Human Coronary Artery Endothelium. Arterioscler. Thromb. Vasc. Biol. 26, P229.
• Smyth JT, DeHaven WI, Jones BF, Mercer JC, Trebak M, Vazquez G, Putney JW Jr. 2006. Emerging perspectives in Store Operated Calcium Entry: Roles of Orai, Stim and TRP. Biochim. Biophys. Acta, 1763, 1147-1160.
• Trebak M, Lemonnier L, Smyth TS, Vazquez G, Putney JW Jr. 2007. Phospholipase C-coupled receptors and activation of TRPC channels. Handbook of Pharmacology, 179, 593-614.
• Smedlund, K. and G. Vazquez. 2008  Involvement of Native TRPC3 Proteins in ATP-Dependent Expression of VCAM-1 and Monocyte Adherence in Coronary Artery Endothelial Cells.  Arterioscler Thromb Vasc Biol. Nov; 28(11):2049-2055.