How the CUL3‑WNK‑SPAK pathway affects kidney salt and potassium balance
Regulation of renal ion transport by the CUL3-WNK-SPAK pathway
This work looks at how changes in the CUL3‑WNK‑SPAK pathway alter kidney salt and potassium handling in people with inherited forms of high blood pressure.
Quick facts
| Grant type | R01 grant |
|---|---|
| Study type | NIH-funded research |
| Funding institution | Oregon Health & Science University NIH-funded |
| Lab location | 1 site (Portland, United States) |
| Project ID | NIH-11262233 on NIH RePORTER |
What this research studies
Researchers will use lab experiments in cells and mouse models to see how mutant CUL3 proteins change the breakdown of key partners like KLHL3 and thereby alter the WNK‑SPAK‑NCC signaling that controls salt and potassium in the kidney. They will compare different CUL3 mutations (for example CUL3‑Δ9 and CUL3‑Δ474‑477) to understand why some cause severe potassium and blood pressure problems while others cause milder effects. Experiments include measuring protein degradation, testing kidney transporter activity, and examining structural features that make KLHL3 uniquely sensitive. The team aims to connect these molecular changes to the abnormal salt and potassium handling seen in familial hyperkalemic hypertension.
Who could benefit from this research
Good fit: People with familial hyperkalemic hypertension, unexplained high blood pressure with high potassium, or known CUL3, KLHL3, or WNK gene changes would be most relevant to this work.
Not a fit: People with common (non‑genetic) high blood pressure, unrelated kidney diseases, or those on dialysis may not directly benefit from these findings.
Why it matters
Potential benefit: If successful, this work could identify specific molecular targets or genetic markers that help guide treatment or diagnosis for familial hyperkalemic hypertension.
How similar studies have performed: Previous lab and animal work has shown the WNK‑SPAK‑NCC pathway controls salt handling and that CUL3 mutations can cause FHHt, but the detailed effects of different CUL3 variants on KLHL3 and NCC are newly explored.
Where this research is happening
Portland, United States
- Oregon Health & Science University — Portland, United States (Active)
Researchers
- Principal investigator: Mccormick, James a — Oregon Health & Science University
- Study coordinator: Mccormick, James a
About this research
- This is an active NIH-funded research project — typically early-stage science, not a clinical trial accepting patient enrollment.
- Some NIH-funded labs run parallel clinical studies or seek volunteers for related work. To check, contact the principal investigator or institution listed above.
- For full project details, budget, and progress reports, visit the official NIH RePORTER page below.