Patrick MacDonald, PhD
Office: 6-126C Li Ka Shing Centre for Health Research Innovation
Mail: University of Alberta, Edmonton AB T6G 2E1
Associate Professor, Dept. of Pharmacology
Canada Research Chair in Islet Biology
Our laboratory studies the mechanisms controlling the function of hormone secreting cells of the pancreatic islets of Langerhans in health and disease. We are particularly interested in the regulation of insulin secretion from islet beta cells.
Current Research Activities
Several projects are currently being pursued in the lab:
1) Regulation of insulin secretion by isoforms of PI3 kinase. Enzymes known as phosphatidylinositol 3-OH kinases (PI3 kinases) are important regulators of islet function and survival. We are investigating the isoform-specific role(s) of PI3 kinases in the regulation of actin, insulin granule trafficking, and insulin exocytosis.
2) Regulation of insulin secretion by SUMOylation. The covalent post-translational modification of protein targets by the small ubiquitin like modifier (SUMO) proteins, called SUMOylation, regulates target function and localization. We are interested in the role of the SUMOylation pathway in the regulation of insulin secretion and islet survival.
3) The role of voltage-dependent K+ channels and their regulators in beta cells. We continue to examine the role of Kv channels in glucose-stimulated insulin secretion. We are interested in the control of these channels by metabolic and receptor mediated signals, and the role of these channels in the process of exocytosis at the plasma membrane.
4) Cytokine signalling and islet function/survival. We are interested in studying novel pathways to protect islets from dysfunction and death induced by hyperglycemia and inflammatory stimuli. Additionally, cytokines such as IL-1 may have important roles controlling insulin secretion per se.
We use state of the art electrophysiological and imaging approaches, combined with molecular biology and in vivo studies, to examine cellular function and insulin secretion. We use laser TIRF and epi-fluorescence microscopy to examine membrane protein localization, signal transduction and intracellular Ca2+ responses in single islet cells and intact pancreatic islets.
Dr. MacDonald completed his doctoral degree in Physiology at the University of Toronto in 2003. Following this Patrick and his family spent two years in Lund, Sweden, where he held a CIHR post-doctoral fellowship at Lund University. Dr. MacDonald then moved to the Oxford Center for Diabetes, Endocrinology and Metabolism at Oxford University, holding the EFSD/AstraZeneca Fellowship in islet biology for one year before joining the Department of Pharmacology, Faculty of Medicine & Dentistry, University of Alberta in June 2006.
Dai XQ, Manning Fox JE, Chikvashvili D, Casimir M, Plummer G, Hajmrle C, Spigelman AF, Kin T, Singer-Lahat D, Kang Y, Shapiro AMJ, Gaisano HY, Lotan I, MacDonald PE (2012) The Kv2.1 channel regulates insulin secretion from rodent and human islets independent of its electrical function. Diabetologia, 55(6):1709-20. (IPF-7.0)
*Manning Fox JE, Hajmrle C, MacDonald PE (2012) Novel roles of SUMO in pancreatic b-cells: Thinking outside the nucleus. Canadian Journal of Physiology and Pharmacology, 90(6):765-70. (IPF-1.8)
MacDonald PE (2011) Signal integration at the level of ion channel and exocytotic function in pancreatic b-cells. American Journal of Physiology - Endocrinology and Metabolism, 301(6):E1065-9 (IPF-4.7)
Dai XQ, Plummer G, Casimir M, Kang Y, Hajmrle C, Gaisano HY, Manning Fox JE, MacDonald PE (2011) SUMOylation regulates insulin exocytosis downstream of secretory granule docking in rodents and humans. Diabetes, 60(3): 838-47. (IPF-8.9)
Spigelman A, Dai X, MacDonald PE (2010) Voltage-dependent K+ channels are positive regulators of alpha-cell action potential generation and glucagon secretion. Diabetologia, 53(9)-917-26. (IPF-7.0)
Pigeau GM, Kolic J, Ball B, Hoppa M, Wang YW, Ruckle T, Woo M, Manning Fox JE, MacDonald PE (2009) Insulin granule recruitment and exocytosis is dependent on p110γ. Diabetes 58(9):2084-92. (IPF-8.9)
Dai XQ, Kolic J, Marchi P, Sipione S, MacDonald PE (2009) SUMOylation regulates Kv2.1 and modulates pancreatic β-cell excitability. J Cell Sci, 122(6):775-9. (IPF-6.3)
Hanna ST, Pigeau GM, Galvanovskis J, Clark A, Rorsman P, MacDonald PE (2008) Kiss-and-run exocytosis and fusion pores of secretory vesicles in human β-cells. Pflugers Archiv. 457(6):1343-50. (IPF-3.4)
MacDonald PE, De Marinis YZ, Salehi A, Ramracheya R, Johnson PRV, Eliasson L, Rorsman P (2007) A KATP channel-dependent pathway within a-cells regulates glucagon release from both rodent and human pancreatic islets of Langerhans. PLoS Biology 5(6):e143. (IPF-12.5)
MacDonald PE, Braun M, Galvanovskis J, Rorsman P (2006) Release of small transmitters through kiss-and-run fusion pores in rat pancreatic b-cells. Cell Metabolism 4:283-290. (IPF-16.1)
Ms. Jelena Kolic (PhD Student)
Ms. Catherine Hajmrle (PhD Student)
Mr. Claude Fu (PhD Student)
Dr. Marina Casimir (postdoc)
Dr. Mourad Ferdaoussi (postdoc)
Dr. Mercedes Munkonda (postdoc)
Website Links of Interest
Dr. MacDonald's Lab