Michael Butterworth, Ph.D.

  • Associate Professor
  • Department of Cell Biology

Education & Training

  • Ph.D. in Cell Biology from University of Cape Town, Cape Town, South Africa, 2002
  • B.Sc.(Med)(Hons) in Cell Biology from University of Cape Town, Cape Town, South Africa, 1995
  • B.Sc. in Zoology from University of Cape Town, Cape Town, South Africa, 1994

Research Interest Summary

Regulation of epithelial ion channels in human kidney and airway by hormonal mechanisms, including microRNAs.

Research Categories

Research Interests

The major research interest investigates the regulation of the epithelial sodium channel (ENaC) by trafficking and recycling mechanisms. We investigate the regulation of ENaC in two tissues, the distal kidney nephron where upregulation of the channel is associated with volume expansion and hypertension, and human airway where ENaC is linked to cystic fibrosis. The main focus is understanding the cellular regulation of this channel. The research could therefore be classified as cell physiology.

In particular we study how the channel (and related distal nephron transporters) are trafficked to the apical surface membrane in response to a variety of signals, and then what happens to these transporters when they are retrieved from the membrane. Most recently this includes regulation of ENaC by microRNAs. We are currently investigating the regulation of microRNAs by steroid hormones, including aldosterone, and the impact changes in miR levels have on sodium transport regulation. We are using a range of techniques to investigate the effect of aldosterone on miRNA regulation in the kidney, and identify new protein targets that in turn regulate ENaC.

Representative Publications

Edinger. R.S., Coronnello. C., Bodnar, A.J., LaFramboise, W.A., Benos, P.V., Ho, J., Johnson, J.P and  Butterworth, M.B. (2014). Aldosterone regulates microRNAs in the CCD to alter sodium transport. Journal of the American Society of Nephrology. (In Press).

Butterworth, M.B., Zhang, L and Thibodeau, P.H. (2014). Modulation of the Proteolytic Activation of the Epithelial Sodium Channel (ENaC) by a Pseudomonas aeruginosa Protease Inhibitor. PLOS One. 9(6):e100313.

Butterworth M.B., Zhang L., Heidrich E., Myerburg M.M., Thibodeau P.H. (2012). Activation of the epithelial sodium channel (ENaC) by the alkaline protease from Pseudomonas aeruginosa. Journal of Biological Chemistry. 287(39):32556-65.

Edinger, R.S., Bertrand, C.A, Rondandino, C., Apodaca, G.A., Johnson, J.P. and Butterworth, M.B. (2012). The epithelial sodium channel (ENaC) establishes a trafficking vesicle pool responsible for its regulation. PLOS One. 7 (9):e46593.

Butterworth, M.B.; Edinger, R.S.; Silvis, M.R.; Gallo, L.I.; Liang, X.; Apodaca, G.; Frizzell, R.A. and Johnson, J.P. (2012). Rab11b regulates the trafficking and recycling of the epithelium sodium channel (ENaC). American Journal of Physiology – Renal. 302:F581-90.

Myerburg M.M., Harvey P.R., Heidrich E.M., Pilewski J.M., Butterworth M.B. (2010). Acute regulation of ENaC in airway epithelia by proteases and trafficking. American Journal of Respiratory Cell and Molecular Biology. 43(6): 712-9.

Butterworth, M.B.; Edinger, R.S.; Ovaa, H.; Johnson, J.P. and Frizzell, R.A. (2007). The deubiquitinating enzyme UCH-L3 regulates the apical membrane recycling of the epithelial sodium channel. Journal of Biological Chemistry. 282:37885-93

Butterworth, M.B.; Frizzell, R.A.; Johnson, J.P; Peters, K.W. and Edinger, R.S. (2005). PKA-dependant ENaC trafficking requires the SNARE binding protein complexin. American Journal of Physiology-Renal. 285(5):F969-977.

Butterworth, M.B.; Edinger, R.S.; Johnson, J.P and Frizzell, R.A. (2005). Acute ENaC regulation by cAMP in a kidney cell line is mediated by exocytic insertion from a recycling channel pool. Journal of General Physiology. 125: 81-101.

Full List of Publications