Stephanie Mutchler
University of Pittsburgh, PA·Physiology·Early-career
Kidneys keep blood pressure and body fluid volume steady by fine-tuning how much salt and water they keep. Much of this fine-tuning happens in the distal nephron, the last section of the kidney's tubules.
- Fields
Physiology
Medicine & Clinical Research
Biology
- Topics
Piezo1
mechanosensitive ion channels
mechanotransduction
- Grants
- 1 known grant, through May 2031
What they work on
- Determine how aldosterone and the mineralocorticoid receptor regulate Piezo1 levels and activity in the distal nephron, using tdTomato-tagged Piezo1 mice, RNAscope, immunostaining and calcium and current recordings from isolated collecting ducts.
- Test whether Nedd4-2, a protein that marks others for degradation, controls Piezo1 expression, using cell culture models and kidney lysates.
- Test whether tubular Piezo1 protects against fibrosis after unilateral ureteral obstruction, comparing mice lacking Piezo1 in all tubules or only the distal nephron with littermate controls.
- Examine cell cycle arrest, apoptosis and YAP activation in obstructed kidneys, and compare genetic loss of Piezo1 with acute blockade by the channel inhibitor GsMTx4.
More about the research
Cells there constantly feel mechanical forces such as stretch and fluid pressure. Piezo1, an ion channel that opens when a cell is stretched and lets positive ions in, is most abundant in this region. This project asks how Piezo1 is controlled in healthy kidneys and whether it protects them when blockage raises pressure and causes scarring, known as fibrosis.
Why it matters
Kidney fibrosis and disorders of salt and water balance affect blood pressure and kidney health. Showing how Piezo1 is regulated and whether it protects tubules from stretch-induced injury could reveal a therapeutic target for mechanical processes in the kidney. The findings may also apply to other tissues, such as blood vessels.
Known grants
From NIH and NSF research grants. Labs often have other funding we can't see.
Closest labs
Thomas Kleyman
University of Pittsburgh, PA·Physiology
Test whether the delta subunit of the epithelial sodium channel in immune cells drives salt-sensitive hypertension, by transferring dendritic cells and monocytes derived from human induced pluripotent stem cells carrying SCNN1D deletions or mutations into immune-deficient mice.
Wenzheng Zhang
Albany Medical College, NY·Physiology
Identify and validate the unique molecular signature of Aqp2+ progenitor cells — kidney cells expressing the water channel Aquaporin-2 plus V-ATPase subunits B1 and B2 — using fluorescent-protein-based cell sorting and single-cell RNA sequencing.
Yanlin Wang
University of Connecticut, CT·Medicine & Clinical Research
Determine the role of PU.1, a transcription factor that switches on genes in immune cells, in macrophage activation and polarization, using cultured macrophages and mouse models of kidney injury.
The school
University of Pittsburgh: 83 labs on PI Pages, $1.5B a year on research, 403 research doctorates a year.
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