Thomas R. Kleyman, M.D.

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

Education & Training

  • MD from Washington University, 1978
  • B.S. from Syracuse University, 1973

Research Interest Summary

Structure and regulation of epithelial ion channels

Research Categories

Research Interests

Recent work has focused on the identification of sites within the channel's extracellular domain that have key roles in the modulation of channel activity in response to extracellular factors, including Na+, shear stress, and proteases. We are using structural models, in conjunction with functional studies, to elucidate mechanisms by which proteases and external cations regulate epithelial Na+ channel activity. We have identified novel functional human epithelial Na+ channel variants, and will be assessing how these variants affect renal Na+ handling and blood pressure in rodent models. We are examining mechanisms by which mechanical forces regulate epithelial sodium channels and large conductance Ca2+ activated potassium channels.

Representative Publications

Bruns, J.B., M.D. Carattino, S. Sheng, A.B. Maarouf, O.A. Weisz, J.M. Pilewski, R.P. Hughey and T.R. Kleyman. Epithelial Na+ channels are fully activated by furin- and prostasin-dependent release of an inhibitory peptide from the gamma subunit. J. Biol. Chem. 282: 6153-6160, 2007. PMID: 17199078

Carattino, M.D., C.J. Passero, C.A. Steren, A.B. Maarouf, J.M. Pilewski, M.M. Myerburg, R.P. Hughey and T.R. Kleyman. Defining an inhibitory domain in the alpha subunit of the epithelial sodium channel. Am. J. Physiol. 294: F47-F52, 2008. PMID: 18032549

Passero, C.J., G.M. Mueller, H. Rondon-Berrios, R.P. Hughey and T.R. Kleyman. Plasmin activates epithelial Na+ channels by cleaving the γ subunit. J. Biol. Chem. 283: 36586–36591, 2008 PMC2605981

Kashlan, O.B., J.L. Adelman, S. Okumora, R.P. Hughey, T.R. Kleyman and M. Grabe. Constraint based, homology model of the extracellular domain of the epithelial Na+ channel subunit reveals a mechanism of channel activation by proteases. J. Biol. Chem. 286: 649-660, 2011. PMC3013024

Kashlan, O.B., B. M. Blobner, Z. Zuzek, M.D. Carattino and T.R. Kleyman. Inhibitory Tract Traps the Epithelial Na+ Channel in a Low Activity Conformation. J. Biol. Chem. 287:20720-6, 2012. PMC3370254

Chen, J., T.R. Kleyman and S. Sheng. Gain-of-function variant of the human epithelial sodium channel. Am. J. Physiol. 304:F207-13, 2013. PMC3543625

Wang, Z., A.R. Subramanya, L.M. Satlin, N.M. Pastor-Soler, M.D. Carattino, and T.R. Kleyman. Regulation of large conductance Ca2+- activated K+ channels by WNK4 kinase. Am J. Physiol. 305:C846-53, 2013 PMC3798677

Shi, S. and T.R. Kleyman. Gamma subunit second transmembrane domain contributes to epithelial sodium channel gating and amiloride block. Am J. Physiol. 305: F1585-F1592, 2013. PMC3882368

Chen, J., T.R. Kleyman and S. Sheng. Deletion of α-subunit exon eleven of the epithelial Na+ channel reveals a regulatory module. Am J. Physiol. 306:F561-F567, 2014. PMC3949035

Mukherjee, A., G.M. Mueller, C.L. Kinlough, N. Sheng, Z. Wang, S.A. Mustafa, O.B. Kashlan, T.R. Kleyman and R.P. Hughey. Cys-palmitoylation of the gamma subunit has a dominant role in modulating activity of the epithelial sodium channel. J. Biol. Chem. 289, 14351-14359, 2014. PMC4022901

Full List of Publications