Thomas Kleyman, MD

  • Chief, Renal-Electrolyte Division
  • Sheldon Adler Professor of Medicine
  • Professor of Medicine and of Cell Biology and Physiology
  • Professor of Pharmacology and Chemical Biology

Education & Training

  • Medical School – Washington University – MD
  • Residency – Presbyterian Hospital New York – Internal Medicine
  • Fellowship – Presbyterian Hospital New York - Nephrology

Research Grants

NIH Grants:  R01, R37, P30, T32, T35

Research Summary

Dr. Kleyman’s research efforts are primarily directed at the study of epithelial Na channels (ENaCs) and large conductance Ca2+ activated K (BK) channels. Recent work has focused on elucidating mechanisms by which extracellular proteases, small ions, and mechanical forces modulate ENaC gating. He is studying how ENaC modification by glycans and palmitate affect channel trafficking and activity. His group as identified novel functional human ENaC variants and are assessing how these variants affect blood pressure in rodent models and humans. Studies are also directed at examining the regulation of BK channels in renal collecting tubules by WNK kinases and by dietary potassium. Dr. Kleyman serves as the director of our Pittsburgh Center for Kidney Research and directs T32 and T35 training grants.

Representative Publications

  1. Webb, TN, Carrisoza-Gaytan, R, Montalbetti, N, Rued, A, Roy, A, Socovich, AM, Subramanya, AR, Satlin, LM, Kleyman, TR, Carattino, MD. Cell Specific Regulation of L-WNK1 by Dietary K+. American Journal of Physiology. 2016; 310: F15-26.
  2. Kashlan, OB, Blobner, BM, Zuzek, Z, Tolino, M, Kleyman, TR. Na+ inhibits the epithelial Na+ channel by binding to a site in an extracellular acidic cleft. Journal of Biological Chemistry. 2015; 290: 568-576.
  3. Mukherjee, A, Mueller, GM, Kinlough, CL, Sheng, N, Wang, Z, Mustafa, SA, Kashlan, OB, Kleyman, TR, Hughey, RP. Cys-palmitoylation of the gamma subunit has a dominant role in modulating activity of the epithelial sodium channel. Journal of Biological Chemistry. 2014; 289: 14351-14359.
  4. Chen, J, Kleyman, TR, Sheng, S. Gain-of-function variant of the human epithelial sodium channel. American Journal of Physiology. 2013; 304: F207-213.
  5. Kashlan, OB, Blobner, BM, Zuzek, Z, Carattino, MD, Kleyman, TR. Inhibitory tract traps the epithelial Na+ channel in a low activity conformation. Journal of Biological Chemistry. 2012; 287: 20720-20726.
  6. Kashlan, OB, Adelman, JL, Okumora, S, Hughey, RP, Kleyman, TR, Grabe, M. Constraint based, homology model of the extracellular domain of the epithelial Na+ channel alpha subunit reveals a mechanism of channel activation by proteases. Journal of Biological Chemistry. 2011; 286: 649-660.
  7. Passero, CJ, Mueller, GM, Rondon-Berrios, H, Hughey, RP, Kleyman, TR. Plasmin activates epithelial Na+ channels by cleaving the ? subunit. Journal of Biological Chemisty. 2008; 283: 36586-36591.
  8. Carattino, MD, Sheng, S, Bruns, JB, Pilewski, JM, Hughey, RP, Kleyman, TR. The epithelial Na+ channel is blocked by a peptide derived from proteolytic processing of its alpha subunit. Journal of Biological Chemistry. 2006; 281: 18901-18907.
  9. Carattino, MD, Sheng, S, Kleyman,TR. Epithelial Na+ channels are activated by laminar shear stress. Journal of Biological Chemistry. 2004; 279: 4120-4126.
  10. Hughey, RP, Bruns, JB, Kinlough, CL, Harkleroad, KL, Tong, Q, Carattino,MD, Johnson, JP, Stockand, JD, Kleyman, TR. Epithelial sodium channels are activated by furin-dependent proteolysis. Journal of Biological Chemistry. 2004; 279: 18111-18114.