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Lab personnel

  • Elijah Atta Manu

    Investigating the mechanisms of how a-ENaC inhibits breast cancer cell proliferation and migration

  • Wey Qi Chin

    The role of the alpha-epithelial sodium channel in breast cancer

  • Professor Fiona McDonald

    Kidney control of blood pressure

  • Priyanka Singh

    Investigating the role of Alpha ENaC in breast cancer drug response and immune modulation

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 Associate Professor 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

Research interests

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.

Expertise

  • Protein-protein interaction assays, Ussing chamber, molecular and cellular biology

Projects

  • 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

Current funding

  • University of Otago Research Grant

Collaborators

  • Associate Professor Ezra Burstein, University of Texas Southerwestern Medical Center
  • Professor Peter Snyder, University of Iowa, USA
  • Dr Shaun Lott, School of Biological Sciences, University of Auckland, NZ
  • Associate Professor Teesdale-Spittle, School of Biological Sciences, Victoria University of Wellington, NZ

Teaching

Selected publications

Logue, M., Farquhar, R. E., Eckhoff-Björngard, Y., Cheung, T. T., Devor, D. C., McDonald, F. J., & Hamilton, K. L. (2023). The exocyst complex is required for the trafficking and delivery of KCa3.1 to the basolateral membrane of polarized epithelia. American Journal of Physiology: Cell Physiology. Advance online publication. doi: 10.1152/ajpcell.00374.2022

McQueen, S., Ware, A., Cunliffe, H., & McDonald, F. (2023). Overexpression of the alpha subunit of the epithelial sodium channel in MDAMB231 breast cancer cells reduces cell migration and proliferation.   Cancer Research, 83(Suppl. 5), P2-16-07.  doi: 10.1158/1538-7445.SABCS22-P2-16-07

McQueen, S. R. A., Cunliffe, H. E., & McDonald, F. J. (2022). Alpha-ENaC overexpression in MDAMB231 breast cancer cells reduces cell migration and proliferation.  In L. Wilson, H. Harcombe, P. Jayakaran, L. Burga, J. Antony, K. Morgaine, M. Garelja, A. Middleton, M. Anwar & T. Milne (Eds.), Proceedings of the 263rd Otago Medical School Research Society (OMSRS) Meeting: PhD Student Speaker Awards. Dunedin, New Zealand: OMSRS. Retrieved from https://ourarchive.otago.ac.nz/handle/10523/12839

McDonald, F. J., Harris, J. J., Slatter, T. L., Cunliffe, H. E., & Ware, A. W. (2022, August). Epithelial sodium channel regulates breast cancer cell proliferation. Verbal presentation at the Cancer Satellite Meeting: Queenstown Research Week, Queenstown, New Zealand.

Ware, A. W., Cheung, T. T., McQueen, S. R. A., Chin, W. Q., Cunliffe, H. E., & McDonald, F. J. (2022, August-September). The role of the epithelial sodium channel (ENaC) in breast cancer.  Poster session presented at the New Zealand Medical Sciences Congress (MedSci), Queenstown, New Zealand.

Chin, W. Q., Ware, A., McDonald, F., & Fronius, M. (2022, August-September). Epithelial-mesenchymal plasticity and breast cancer: A role for the epithelial sodium channel? Poster session presented at the New Zealand Medical Sciences Congress (MedSci), Queenstown, New Zealand.

Kularathna, B. A. S. A., McDonald, F. J., & Ware, A. W. (2022, August-September). The role of ENaC in breast cancer migration: An implication towards cancer metastasis. Poster session presented at the New Zealand Medical Sciences Congress (MedSci), Queenstown, New Zealand.

Loke, J. J., McDonald, F. J., & Ware, A. W. (2022, August-September). EMP-associated signalling genes regulated by ENaC in breast cancer.  Poster session presented at the New Zealand Medical Sciences Congress (MedSci), Queenstown, New Zealand.

Logue, M. J. E., Cheung, T. T., Devor, C. E., Devor, D. C., McDonald, F. J., & Hamilton, K. L. (2022, August-September). The differential role of retromer in the trafficking of the Ca2+-activated K+ channels KCa2.3 and KCa3.1. Verbal presentation at the New Zealand Medical Sciences Congress (MedSci), Queenstown, New Zealand.

McQueen, S. R. A., Cunliffe, H. E., & McDonald, F. J. (2022, August-September). Alpha-ENaC overexpression in MDAMB231 breast cancer cells reduces cell migration and proliferation. Verbal presentation at the New Zealand Medical Sciences Congress (MedSci), Queenstown, New Zealand.

Farquhar, R. E., Cheung, T. T., Logue, M. J. E., McDonald, F. J., Devor, D. C., & Hamilton, K. L. (2022). Role of SNARE Proteins in the Insertion of KCa3.1 in the Plasma Membrane of a Polarized Epithelium. Frontiers in Physiology, 13, 905834.  doi: 10.3389/fphys.2022.905834

Paudel, P., van Hout, I., Bunton, R. W., Parry, D. J., Coffey, S., McDonald, F. J., & Fronius, M. (2022). Epithelial sodium channel δ subunit is expressed in human arteries and has potential association with hypertension. Hypertension, 79(7), 1385-1394.  doi: 10.1161/hypertensionaha.122.18924

McDonald, F. J. (2021, November). Epithelial sodium channel regulates breast cancer cell proliferation. Verbal presentation at the New Zealand Breast Cancer Symposium (NZBCS), [Online].

McDonald, F. (2021, March). Unravelling control pathways for sodium channels: Implications for blood pressure. University of Otago, Dunedin, New Zealand. [Inaugural Professorial Lecture].

Logue, M., Cheung, T., Devor, C., Devor, D., McDonald, F., & Hamilton, K. (2021). The Role of Retromer in the Trafficking of the Ca2+- activated K+ channels KCa2.3 and KCa3.1.   FASEB Journal, 35(Suppl. 1).  doi: 10.1096/fasebj.2021.35.S1.04094

McQueen, S., Ware, A., Cunliffe, H., & McDonald, F. (2021). The influence of the epithelial sodium channel in breast cancer cells.   FASEB Journal, 35(Suppl. 1).  doi: 10.1096/fasebj.2021.35.S1.05028

Paudel, P., McDonald, F., & Fronius, M. (2021). Vascular ENaC in human arteries and its role in hypertension.   FASEB Journal, 35(Suppl. 1).  doi: 10.1096/fasebj.2021.35.S1.02625

Ware, A. W., Harris, J. J., Slatter, T. L., Cunliffe, H. E., & McDonald, F. J. (2021). The epithelial sodium channel has a role in breast cancer cell proliferation. Breast Cancer Research & Treatment, 187, 31-43.  doi: 10.1007/s10549-021-06133-7

Paudel, P., McDonald, F. J., & Fronius, M. (2021). The δ subunit of epithelial sodium channel in humans: A potential player in vascular physiology. American Journal of Physiology: Heart & Circulatory Physiology, 320, H487-H493.  doi: 10.1152/ajpheart.00800.2020

McDonald, F. J. (2020). Explosion in the complexity of membrane protein recycling. American Journal of Physiology: Cell Physiology, 320, C483-C494. doi: 10.1152/ajpcell.00171.2020

Paudel, P., McDonald, F., & Fronius, M. (2020). Epithelial Na+ channel (ENaC) in human arteries: An emerging player in hypertension.   FASEB Journal, 34(Suppl. 1).  doi: 10.1096/fasebj.2020.34.s1.03713

Scott, M. L., Cheung, T. T., Hamilton, K. L., & McDonald, F. J. (2020). Sorting nexins 1, 2, 3 and 17 regulate epithelial sodium channel trafficking.   FASEB Journal, 34(Suppl. 1).  doi: 10.1096/fasebj.2020.34.s1.07065

Cheung, T. T., Geda, A. C., Ware, A. W., Rasulov, S. R., Tenci, P., Hamilton, K. L., & McDonald, F. J. (2020). Retromer is involved in epithelial Na+ channel trafficking. American Journal of Physiology: Renal Physiology, 319, F895-F907.  doi: 10.1152/ajprenal.00198.2019

Ware, A. W., Rasulov, S. R., Cheung, T. T., Lott, J. S., & McDonald, F. J. (2020). Membrane trafficking pathways regulating the epithelial sodium channel, ENaC. American Journal of Physiology: Renal Physiology, 318, F1-F13.  doi: 10.1152/ajprenal.00277.2019

Walters, C., Hamilton, K. L., & McDonald, F. J. (2019, September). The effect of Rab7 on the trafficking of the epithelial sodium channel.  Poster session presented at the Medical Sciences Congress (MedSci), Queenstown, New Zealand.

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