Graham F. Wagner
Professor
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PH.D. Simon Fraser University |
My research involves the stanniocalcins (STCs), a hormone family that comprises two known members, STC-1 and STC-2. The STCs are glycoprotein hormones that are widely distributed throughout the animal kingdom, in both vertebrates and invertebrates. I work primarily on STC-1.
STC-1 discovery and function. We isolated and characterized STC-1 in 1986, originally from fish endocrine glands known as the corpuscles of Stannius. Consequently much of our early work is devoted to STC-1 function in fish using rainbow trout as an experimental model. We now know that STC-1 from fish corpuscles of Stannius regulates calcium balance through its effects on transporters in the gills, gut and kidneys. Fish STC-1 is also expressed in trace amounts in organs such as kidney and ovary. However, its functions here have not yet been addressed. We continue to study STC-1 from an evolutionary perspective in fishes and aquatic invertebrates (leeches), but our major focus now is on mammalian STC-1 and its role in kidney function.
Mammalian STC-1. We were also involved in the initial identification of mammalian STC-1 in 1995. And like the fish hormone, it too is expressed in different organs (kidney, heart, lung, brain, ovary, muscle). However, as far as we know mammals do not have STC-1 producing glands that are comparable to the fish corpuscles of Stannius. Thus far, mammalian STC-1 has proven to be a multi-functional hormone, having different functions depending on tissue type. These include renal salt and water transport, reproduction, (ovary, uterus, mammary gland), embryonic development, cell survival and cancer.
STC-1 targeting. Moreso perhaps than any other hormone, STC-1 is heavily sequestered by target cell organelles. These include the mitochondria in liver, kidney and muscle where STC-1 uncouples oxidative phosphorylation. Secondly, STC-1 is sequestered by the nuclei of milk producing mammary gland cells to increase milk fat content. Lastly, STC-1 is sequestered on the lipid droplet hemi-membranes in steroidogenic cells where it regulates hormone synthesis. Organelle targeting of STC-1 occurs in both mammals and fish (Richards et at., 2012).
Our current focus is on the role of STC-1 in extracellular fluid (ECF) balance. Intra-cerebral injections of STC-1 into the nucleus of the solitary tract lower heart rate and blood pressure in the rat (Ciriello et al., 2012). In addition, the renal STC-1 gene is highly upregulated by water deprivation in both rats and mice (Turner et al., 2010, 2011) under the control of pituitary-derived vasopressin (Law et al., 2012). These more recent findings are indicative of STC-1 having specific roles in ECF balance. The precise nature of these roles is our current area of focus in the laboratory.
Greenwood MP, Flik G, Wagner GF, Balment RJ. 2009. The corpuscles of Stannius, calcium-sensing receptor, and stanniocalcin: responses to calcimimetics and physiological challenges. Endocrinology. 150, 3002-3010.
Turner, J., Sazonova, O., Wang, H., Pozzi, A., and Wagner, G.F. 2010. Induction of the renal stanniocalcin-1 gene in rodents by water deprivation. Mol. Cell. Endocrinol. 328, 8-15.
Turner, J., Xiang, F.L., Feng, Q., and Wagner, G.F. 2011. The renal stanniocalcin-1 gene is differentially regulated by hypertonicity and hypovolemia in the rat. Mol. Cell. Endocrinol. 331, 150-7.
Law, AY, Wong, CK, Turner, J, Gonzalez, AA, Prieto, MC, Wagner, GF. 2012. Vasopressin controls stanniocalcin-1 gene expression in rat and mouse kidney. Mol Cell Endocrinol. 348; 183-8.
Richards, TC, Fenton, AL, Sayed, R, Wagner, GF. 2012. Characterization of stanniocalcin-1 receptors in the rainbow trout. ISRN Endocrinology (Article ID: 257841, 11 pages, doi 10.540/2012/257841).
Ciriello, J. Oiamo, TH., Moreau, JM., Turner, JK. and Wagner, GF. 2012. Effects of the calcium-regulating glycoprotein hormone stanniocalcin-1 within the nucleus of the solitary tract on arterial pressure and the baroreceptor reflex. Neuroscience 207, 88-102).
