What We Do

Research Focus 1

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 2 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 so the research could be classified as cell physiology.

In particular we study how the channel (and related distal nephron transporters) are 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. This work has characterized a number of novel regulators for ENaC that are involved in the trafficking and recycling of the channel (see publications for examples), and the process is illustrated in the schematic below.

In understanding how cells move this channel around when required (normally by hormonal or local signaling cues) we have focused on the role of small GTPases, deubiquitinating enzymes (DUBs) and most recently microRNAs. 

Most of the work centers on the kidney, but we make use of the findings in this tissue to compare/contrast the regulation of this transporter in the airway.

The work has been expanded to include other distal nephron transporters namely, aquaporin 2, ROMK (potassium channel) and the urea transporter to see if what we observe for ENaC trafficking is applicable to these other channels found in the same cells.

Research Focus 2

More recently, and in collaboration with several other labs, we are undertaking a new project looking at the role of microRNAs in the regulation of sodium transport. MicroRNAs are short (22nt) pieces of non-coding RNA that bind to messenger RNAs to repress protein translation. The process is illustrated in the schematic below.

We are currently investigating the regulation of microRNAs by the steroid hormone, aldosterone, and its impact on ENaC 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. Preliminary findings from this work has been presented recently at a number of national and international conferences.