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Thomas Kleyman

University of Pittsburgh, PA·Physiology

The kidney keeps the body's internal chemistry in balance: it decides how much salt, potassium, acid and water leave in the urine. When kidney function fails, that balance breaks down.

Fields

Physiology

Medicine & Clinical Research

Biophysics

Topics

kidney physiology

nephron

cortical collecting duct

Grants
3 known grants, through Jun 2029

What they work on

  1. 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.
  2. Determine how ENaC regulators shape immune responses to dietary salt, by transferring dendritic cells and monocytes from mice with mutations altering sodium self-inhibition, protease cleavage or cysteine palmitoylation, and recording channel function by patch clamp.
  3. Define where Piezo1, a stretch-activated ion channel, is located in the aldosterone-sensitive distal nephron and how its expression changes during development and with low-potassium, high-potassium or aldosterone treatment.
  4. Test whether Piezo1 activators and inhibitors alter intracellular calcium, sodium and potassium transport, and BK channel activity in cortical collecting ducts isolated from mice on control or high-potassium diets.
  5. Determine whether deleting Piezo1 specifically in intercalated cells changes whole-animal potassium handling and the flow-induced calcium and ion transport responses of microperfused collecting ducts.
  6. Operate core facilities that supply US kidney investigators with physiology, model-system and advanced imaging resources, and run a summer undergraduate enrichment program and a lay education program on kidney function and disease.

More about the research

Work here centers on the ion channels, protein pores in cell membranes that let charged particles pass, that carry out this balancing act in the final segments of the kidney tubule, and on how they influence blood pressure and potassium levels. Alongside these laboratory projects, the lab directs a national center that supplies kidney researchers across the country with specialized tools and expertise.

Why it matters

Sodium handling in the kidney and in immune cells sets blood pressure, and potassium imbalances are a common and dangerous complication of kidney disease. Pinpointing how specific ENaC subunits, their regulators and the flow sensor Piezo1 control salt and potassium transport could reveal drug targets for salt-sensitive hypertension and for potassium disorders. The national resource center supplies tools, imaging and training that other kidney laboratories across the country can use.

Known grants

From NIH and NSF research grants. Labs often have other funding we can't see.

ENaC regulation and its role in blood pressure homeostasis

NIH · May 1996 – Jun 2029

Pittsburgh Center for Kidney Research

NIH · Sep 2023 – Jun 2028

Role of piezo channels in intercalated cells

NIH · Apr 2022 – Mar 2027

Closest labs

Stephanie Mutchler

University of Pittsburgh, PA·Physiology·Early-career

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.

Nicholas Ferreri

New York Medical College, NY·Physiology

Determine which kidney tubule cells produce the TNF that limits salt-driven blood pressure rises, using mice lacking TNF in the thick ascending limb or distal nephron plus cell-specific TNF-silencing lentiviruses.

Paul Welling

Johns Hopkins University, MD·Physiology

Test whether regulated expression of the ROMK potassium channel in the DCT2 and connecting tubule segments controls body potassium balance, using mice in which ROMK can be switched off in specific cell types.

The school

University of Pittsburgh: 83 labs on PI Pages, $1.5B a year on research, 403 research doctorates a year.

More about University of Pittsburgh

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