Tse, Frederick W - University of Alberta - Department of Pharmacology

个人简介

BSc (zoology), University of Toronto, 1980 MSc (zoology) University of Toronto, 1981 PhD (physiology), University of Toronto, 1987

研究领域

My lab's main focus is the mechanisms of exocytosis: a process that allows the fusion of small vesicles inside a cell with the surface (plasma) membrane of the cell. This process underlies the secretion of neurotransmitters and hormones that are previously packaged into secretory vesicles. Tse We have been employing a combination of biophysical approaches to precisely trigger and monitor exocytosis. These approaches include flash photolysis of "caged-Ca2+", membrane capacitance measurement in whole-cell mode, detection of catecholamine release from individual vesicles by carbon fiber amperometry. Recently we discovered that cholesterol, a lipid that is normally enriched in both the vesicular and plasma membranes of cells, can selectively influence one stage of exocytosis: when the lumen of a secretory vesicle is just connected to the extracellular space via a very small structure called the fusion pore (see figure on this page). We are collaborating with labs in the Faculty of Medicine to exploit RNA interference techniques (involving delivery by a virus) for acutely suppressing the expression of a cholesterol transporter that is recently discovered to be selectively expressed at secretory vesicles of endocrine cells. The effects of this lipid manipulation will be examined in two cells models that both secrete catecholamine: (1) Chromaffin cells of the adrenal gland, which mediates the key endocrine output of "stress" catecholamines (adrenalin and noradrenalin) in our body (2) Glomus (chemosensory) cells of the carotid body, which secrete dopamine (as well as other transmitters) for local para/autocrine signalling in response changes in arterial O2 and CO2.

近期论文

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Lee AK, Tse FW and Tse A. (2015) Arginine vasopressin (AVP) potentiates the stimulatory action of CRH on pituitary corticotropes via a protein kinase C dependent reduction of the background TREK-1 current. Endocrinology [Epub ahead of print]. PMID: 26248219. Tse A, Lee AK, Tse FW. (2013) Influence of arachidonic acid on the endocrine response to stress. In: Arachidonic acid: dietary sources and general functions, Dumancas GG, Murdianti BS, Lucas (Eds.), Nova Science Publishers Inc, NY., Chapter 4, 51-62. Tse A, Yan L, Lee AK, Tse FW. (2012) Autocrine and paracrine actions of ATP in rat carotid body. Can J Physiol Pharmacol 90(6):705-711. PMID: 22509744. Wang N, Lee AK, Yan L, Simpson MR, Tse A, Tse FW. (2012) Granule matrix property and rapid "kiss-and-run" exocytosis contribute to the different kinetics of catecholamine release from carotid glomus and adrenal chromaffin cells at matched quantal size. Can J Physiol Pharmacol 90(6):791-801. PMID: 22506963. Tse A, Lee AK, Yan L, Tse FW. (2012) Influence of cholesterol on cellular signaling and fusion pore kinetics. J Mol Neurosci 48(2):395-401. PMID: 22467040. Tse A, Lee AK, Tse FW. (2012) Ca2+ signaling and exocytosis in pituitary corticotropes. Cell Calcium 51(3-4):253-259. PMID: 22225940. Yan L, Lee AK, Tse FW, Tse A. (2012) Ca2+ homeostasis and exocytosis in carotid glomus cells: role of mitochondria. Cell Calcium 51(2):155-163. PMID: 22209034. Lee AK, Yeung-Yam-Wah V, Tse FW and Tse A (2011) Cholesterol elevation impairs glucose-stimulated Ca(2+) signaling in mouse pancreatic β-cells. Endocrinology 152(9):3351-3361. PMID: 21712366. Wang, N., Kwan, C., Gong, X., Posse de Chaves, E., Tse, A. & Tse, F.W. (2010) Influence of cholesterol on catecholamine release from the fusion pore of large dense core chromaffin granules. J. Neurosci. 30:3904-3911. PMID: 20237261.