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Kir4.1-dependent mechanisms of potassium sensing and signaling in the thick ascending limb

Award Number: K08DK147727
ORGANIZATION: NATIONAL INSTITUTE OF DIABETES & DIGESTIVE & KIDNEY DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: TRAINING/TRAINEESHIP
PERIOD OF PERFORMANCE START DATE: 05/01/2026
PERIOD OF PERFORMANCE END DATE: 01/31/2031

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Kir4.1-dependent mechanisms of potassium sensing and signaling in the thick ascending limb - PROJECT ABSTRACT The thick ascending limb (TAL) of the nephron plays a central role in sodium and potassium homeostasis, but its ability to adapt to dietary potassium stress remains poorly defined. Preliminary data indicate that the inwardly rectifying potassium channel Kir4.1 is selectively expressed in distinct TAL cell populations and may function as a basolateral potassium sensor. This career development proposal tests the hypothesis that Kir4.1 regulates TAL transport and drives structural and transcriptional remodeling in response to changes in extracellular potassium concentration that accompany extremes of dietary potassium intake. To test this hypothesis, the research integrates TAL-specific Kir4.1 knockout models with advanced imaging, metabolic phenotyping, tubule perfusion, and single-nucleus RNA sequencing. Aim 1 tests the hypothesis that Kir4.1 enables basolateral potassium sensing and thereby regulates TAL sodium and potassium handling. Aim 2 tests the hypothesis that Kir4.1-expressing TAL cells undergo structural and transcriptional remodeling— including phenotypic switching, apoptosis, or proliferation—in response to extreme dietary potassium stress. These studies aim to close a key knowledge gap in segment-specific potassium sensing and may reveal new therapeutic targets for hypokalemic disorders and diuretic resistance. The candidate’s long-term objective is to lead an independent research program focused on renal epithelial transport in genetic and acquired tubulopathies. This K08 award will provide the mentored training necessary to support this transition, with structured development in electrophysiology, high-resolution imaging, and transcriptomic analysis. The training environment at Oregon Health and Science University offers strong mentorship, institutional support, and access to leading expertise in renal physiology to foster the candidate’s development as a physician-scientist.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2026 ( Subtotal = $167,400 )
2026	2026	OREGON HEALTH & SCIENCE UNIVERSITY	3181 SW SAM JACKSON PARK RD	PORTLAND	OR	97239	MULTNOMAH	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	1	4/14/2026	NEW	$167,400
														Subtotal = $167,400

Grand Total All Awards = $167,400

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Kir4.1-dependent mechanisms of potassium sensing and signaling in the thick ascending limb

Award Number: K08DK147727

ORGANIZATION: NATIONAL INSTITUTE OF DIABETES & DIGESTIVE & KIDNEY DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: TRAINING/TRAINEESHIP

PERIOD OF PERFORMANCE START DATE: 05/01/2026

PERIOD OF PERFORMANCE END DATE: 01/31/2031

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