Department of Medicine
Faculty Profiles by Division

Division of Renal-Electrolyte

Faculty Profiles
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photo Thomas R. Kleyman, MD

Renal-Electrolyte

Chief, Renal-Electrolyte Division

Sheldon Adler Professor of Medicine

Professor of Cell Biology

Professor of Pharmacology and Chemical Biology

Email: kleyman@pitt.edu

Phone: 412-647-3121
Contact
Office: A919 Scaife Hall
3550 Terrace Street
Pittsburgh, PA 15261
 
Phone: 412-647-3121
Fax: 412-648-9166
E-mail: kleyman@pitt.edu
Administrative Assistant:
Carmela Londino
Address: A919 Scaife Hall
3550 Terrace Street
Phone: 412-647-3118
Education and Training
Education
BS, Syracuse University, 1973
M.D., Washington University, St. Louis, MO, 1978
M.A. (honoris causa), University of Pennsylvania, 1997
Training
Internal Medical Residency, Presbyterian Hospital, New York, 1981
Nephrology Fellowship, Presbyterian Hospital, New York, 1983
Research Interest
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.
Educational Interest
Dr. Kleyman's main educational interests are focused on fluid and electrolyte Disorders.
Publications
For my complete bibliography, Click Here.
Selected Publications:
Kleyman, T. R., Kashlan, O. B., Sheng, S. Rare Variants in Genes Encoding Subunits of the Epithelial Na+ Channel Are Associated with Blood Pressure and Kidney Function in the TOPMed Project. Hypertension. 2022; 79(11): 2573–2582.
Kleyman, T. R., Baty, C. J., Carattino, M. D., Montalbetti, N., Sheng, S., Shi, S. Functional characterization of ion channels expressed in kidney organoids derived from human induced pluripotent stem cells. American Journal of Physiology - Renal Physiology. 2022; 323(4): F479-F491.
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.
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.
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.
Chen, J, Kleyman, TR, Sheng, S. Gain-of-function variant of the human epithelial sodium channel. American Journal of Physiology. 2013; 304: F207-213.
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.
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.
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.
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.
Sponsored Research/Activities
Title: ENaC regulation and its role in blood pressure homeostasis
Role: Principal Investigator
Funding Agency: National Heart, Lung, & Blood Institute/ National Institute of Health
Grant Number: R01 HL147818
Start Year: 2019
End Year: 2023
Title: Platform for Real-Time, Continuous Measurement of Na and K Concentrations
Role: Principal Investigator
Funding Agency: Bionymer / Bionymer
Grant Number: CONTRACT
Start Year: 2019
End Year: 2020
Title: Pittsburgh Center for Kidney Research
Role: Principal Investigator
Funding Agency: National Institute of Diabetes, Digestive, & Kidney Disease
Grant Number: P30 DK079307
Start Year: 2018
End Year: 2023
Title: Renal and Epithelial Biology Training Program
Role: Principal Investigator
Funding Agency: National Institute of Diabetes, Digestive, & Kidney Disease
Grant Number: T32 DK061296
Start Year: 2018
End Year: 2023
Title: Maturation of K Transport in the Distal Nephron
Role: Principal Investigator
Funding Agency: Mt. Sinai Medical Center/National Institute of Diabetes, Digestive, & Kidney Disease
Grant Number: R01 DK038470
Start Year: 2015
End Year: 2020
Title: Training in Renal, GI, Endocrine, and Epithelial Biology
Role: Principal Investigator
Funding Agency: National Institute of Diabetes, Digestive, & Kidney Disease
Grant Number: T35 DK065521
Start Year: 2015
End Year: 2020
Title: Role of GRP170 in ENaC Biogenesis and Renal Physiology
Role: Co-Investigator
Funding Agency: National Institute of Diabetes, Digestive, & Kidney Disease
Grant Number: R01 DK117126
Start Year: 2019
End Year: 2024
Title: Brain NaCl-sensing in salt-sensitive hypertension
Role: Co-Investigator
Funding Agency: National Heart, Lung, & Blood Institute
Grant Number: R01 HL145875
Start Year: 2019
End Year: 2023
Notable Achievements
AHA Established Investigatorship Award, 1991
American Society for Clinical Investigation, 1996
Association of American Physicians, 2004
NIH MERIT Award, 2006
Ussing Award Lecture, American Physiological Society, 2008
Robert Schrier Lecture, American Society of Nephrology, 2009
Donald Seldin Lecture, American Heart Association, 2010
Sheldon Alder, MD Chair in Nephrology Research, 2011
Carl W. Gottschalk Distinguished Lectureship, American Physiological Society, 2015

Division Websites

Cardiology

Endocrinology and Metabolism

Gastroenterology, Hepatology and Nutrition

General Internal Medicine

Geriatric Medicine
Hematology/Oncology

Infectious Diseases

Pulmonary, Allergy and Critical Care Medicine

Renal-Electrolyte

Rheumatology and Clinical Immunology

Contact

Department of Medicine
1218 Scaife Hall
3550 Terrace Street
Pittsburgh, PA 15261
Email:  chairoff@pitt.edu
Phone:  412-648-9636
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