Associate Professor Fiona McDonald
Head of Department
Department of Physiology
Otago School of Medical Sciences
University of Otago
PO Box 913
Fax: +64 3 479 7323
Member of Membrane & Ion Transport.
Member of research themes "Functional Genomics, Gene Expression and Proteomics" and Kidney in Health and Disease.
How do proteins find their way to their correct location in a cell? What factors control this "protein trafficking" process? Using the epithelial sodium channel (ENaC), essential for kidney control of blood pressure, we have shown that ubiquitin pathway proteins control the number of ENaCs at the cell surface resulting in changes in Na+ absorption. As part of a protein interaction screen we discovered that COMMD family proteins also regulate ENaC trafficking. The mechanisms and implications of this pathway are under investigation.
Pancreatic acinar cells are responsible for digestive enzyme secretion subsequently necessary for breakdown of ingested food. Unregulated activation of digestive enzymes in the acinar cells of the pancreas can cause cell damage, in a process called pancreatitis. The COMMD10 protein is highly expressed in pancreas and has links to the protein secretory pathway; we are currently investigating the role of COMMD10 in the production and secretion of digestive enzymes from pancreatic acinar cells.
- Protein-protein interaction assays, Ussing chamber, molecular and cellular biology
- Regulation of ENaC by COMMD protein family members.
- Regulation of ENaC by ubiquitin pathway proteins: Nedd8, XIAP.
- Interaction of COMMD1 with the insulin signalling pathway.
- University of Otago Research Grant
- Assoc Prof Ezra Burstein, University of Texas Southerwestern Medical Center
- Prof Peter Snyder, University of Iowa, USA.
- Dr Shaun. Lott, School of Biological Sciences, University of Auckland, NZ.
- A/Prof P. Teesdale-Spittle, School of Biological Sciences, Victoria University of Wellington, NZ.
Previous lab personnel
- Yongfeng Liu, currently postdoctoral fellow Center for Cardiovascular Sciences, Albany Medical Center, USA with Prof Harold Singer
- Ying Ke, Currently postdoctoral fellow with A/Prof Jamie Vandenberg at Victor Chang Cardiac Research Institute, Sydney
- Dominik Wiemuth, Currently postdoctoral fellow with Professor Stefan Grunder, University of Aachen, Germany.
- Joy McIntosh, Currently postdoctoral fellow with Professor Ken McNatty, Victoria University of Wellington.
- Meino Rohlfs, Currently postdoctoral fellow with Dr Michael Schleicher, Ludwig-Maximilians-University, Munich, Germany.
- McDonald, FJ. COMMD1 and ion transport proteins – what is the COMMection? Am. J. Physiol. Cell Physiol. 305: C129-30, 2013.
- Bobby, R., Medini, K., Neudecker, P., Lee, TV., Brimble, MA., McDonald, FJ., Lott, JS., Dingley, AJ. Structure and dynamics of human Nedd4-1 WW3 in complex with the aENaC PY motif, BBA – Proteins and Proteomics, 1834(8):1632-41, 2013.
- Ly, K., McIntosh, CJ., Biasio, W., Liu, YF., Ke, Y., Olson, DR., Miller, JH., Page, R., Snyder, PM., McDonald, FJ., Regulation of the delta and alpha epithelial sodium channel (ENaC) by ubiquitination and Nedd8. J Cell Physiol., 228(11): 2190-2201, 2013.
- Liu, YF., Swart, M., Ke, Y., Ly, K., McDonald, FJ. Functional interaction of COMMD3 and COMMD9 with the epithelial sodium channel. Am. J. Physiol. Renal Physiol. 8 305: F80-89, 2013.
- Starokadomskyy, P., Gluck, N., Li, H., Chen, B., Wallis, M., Maine, GN., Mao, X., Iram W. Zaidi, IW., Hein, MY., McDonald, FJ., Lenzner, S.,Zecha, A., Ropers, H-H., Kuss, AW., McGaughran, J., Gecz, J., Burstein, E. CCDC22 deficiency in humans blunts activation of pro-inflammatory NF-κB signaling. J Clin Invest. 123: 2244-2256, 2013.
- Chang, T., Ke, Y., Ly, K., McDonald,F.J. COMMD1 regulates the delta epithelial sodium channel (δENaC) through trafficking and ubiquitination. Biochem. Biophys. Res. Commun., 411: 506-511, 2011.
- Wiemuth, D., Lott, J.S., Ly, K., Ke, Y., Teesdale-Spittle, P., Snyder, PM., McDonald, F.J. Interaction of the serum and glucocorticoid regulated kinase (SGK1) with the WW domains of Nedd4-2 is required for epithelial sodium channel regulation. PLoSONE 5 (8) e12163, 2010.
- Ke, Y., Butt, A.G., Swart, M., Liu, Y-F, McDonald, F.J. COMMD1 downregulates the epithelial sodium channel through Nedd4-2. Am. J. Physiol. Renal Physiol. 298(6): F1445-1456, 2010.
- Walker, R., Spronken-Smith, R., Bond, C., McDonald, F., Reynolds, J., & McMartin, A. The impact of curriculum change on health sciences first year students' approaches to learning. Instructional Science, DOI:10.1007/S11251-009-9092-y, in press.
- Bedford, J.J., Weggery, S., Ellis, G., McDonald, F.J., Joyce, P.R., Leader, J.P., & Walker, R.J. Lithium-induced nephrogenic diabetes insipidus: renal effects of amiloride. Clinical JASN, 3: 1324-1331 (2008).
- McDonald, F.J. A new SGK1 knockout mouse. American Journal of Physiology Renal Physiology, 294: F1296-F1297 (2008).
- Wiemuth, D., Ke, Y., Rohlfs, M., McDonald, F.J. Epithelial sodium channel (ENaC) is multiubiquitinated at the cell surface. Biochemical Journal, 405: 147-155 (2007).
- HUBS191 - Endocrine lectures, Academic Course Co-ordinator
- PHSL233 - Epithelial signalling and polarity
- PHSL343 - Epithelial sodium channel