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Jerry B. Lingrel
Jerry B. 
Lingrel
, Ph.D.
Professor

University Distinguished Research Professor

B.S., Chemistry , Otterbein College , Westerville , OH

Ph.D., Biochemistry , Ohio State University , Columbus , OH

Postdoctoral Fellow , California Institute of Technology , CA

Our laboratory is interested in gene expression and function primarily in the heart and the vascular system.

Our studies focus on a transcription factor we discovered, KLF2. KLF2 is required for vascular integrity and protects against atherosclerosis. It appears to be a master regulator of vascular function and in endothelial cells, macrophages and T-cells. We have developed animals where this gene can be deleted or over expressed in any cell type and are using this approach to understand various roles that KLF2 plays.

We also study the Na,K-ATPase which is responsible for transporting Na+ out of the cell and K+ in. This gradient drives many other transport processes as well as establishing the electrogenic potential necessary for muscle contraction and nerve function. Using gene targeting, we have demonstrated that the alpha2 isoform plays a critical regulatory role in cardiac and smooth muscle contraction through calcium signaling and is critical for neuron function. In addition, we are characterizing the role this enzyme plays in normal blood pressure regulation during pregnancy and in heart attacks.

Selected Publications:
  • Loreaux, E.L., Kaul, B., Lorenz, J.N., Lingrel, J.B. (2008) Ouabain-Sensitive alpha1 Na,K-ATPase enhances natriuretic response to saline load. J Am Soc Nephrol. Oct;19(10):1947-54.
  • Lorenz, J.N., Loreaux, E.L., Dostanic-Larson, I., Lasko, V., Schnetzer, J.R., Paul, R.J., Lingrel, J.B. (2008) ACTH-induced hypertension is dependent on the ouabain-binding site of the alpha2-Na+-K+-ATPase subunit. Am J Physiol Heart Circ Physiol. Jul;295(1):H273-80.
  • Wu, J., Bohanan, C.S., Neumann, J.C., Lingrel, J.B. (2008) KLF2 transcription factor modulates blood vessel maturation through smooth muscle cell migration. J Biol Chem. Feb 15;283(7):3942-50.
  • Moseley, A.E., Williams, M.T., Schaefer, T.L., Bohanan, C.S., Neumann, J.C., Behbehani, M.M., Vorhees, C.V., Lingrel, J.B. (2007) Deficiency in Na,K-ATPase alpha isoform genes alters spatial learning, motor activity, and anxiety in mice. J Neurosci. Jan 17;27(3):616-26.
  • Basu, P., Lung, T.K., Lemsaddek, W., Sargent, T.G., Williams, D.C. Jr., Basu, M., Redmond, L.C., Lingrel, J.B., Haar, J.L., Lloyd, J.A. (2007) EKLF and KLF2 have compensatory roles in embryonic beta-globin gene expression and primitive erythropoiesis. Blood. Nov 1;110(9):3417-25.
  • Lorenz, J.N., Dostanic-Larson, I., Shull, G.E. and Lingrel, J.B. (2006) Ouabain inhibits tubuloglomerular feedback in mutant mice with ouabain-sensitive alpha1 Na,K-ATPase. J. Am. Soc. Nephrol. 17(9):2457-63.
  • Carlson, C.M., Endrizzi, B.T., Wu, J., Ding, X., Weinreich, M.A., Walsh, E.R., Wani, M.A., Lingrel, J.B., Hogquist, K.A. and Jameson, S.C. (2006) Kruppel-like factor 2 regulates thymocyte and T-cell migration. Nature 442(7100):299-302.
  • Huddleson, J.P., Ahmad, N. and Lingrel, J.B. (2006) Up-regulation of the KLF2 transcription factor by fluid shear stress requires nucleolin. J. Biol. Chem. 281(22):15121-8.
  • Dostanic-Larson, I., Lorenz, J.N., Van Huysse, J.W., Neumann, J.C., Moseley, A.E. and Lingrel, J.B. (2006) Physiological role of the alpha1- and alpha2-isoforms of the Na+-K+-ATPase and biological significance of their cardiac glycoside binding site. Am. J. Physiol. Regul. Integr. Comp. Physiol. 290(3):R524-8.
  • Dostanic-Larson, I., Van Huysse, J.W., Lorenz, J.N. and Lingrel, J.B. (2005) The highly conserved cardiac glycoside binding site of Na,K-ATPase plays a role in blood pressure regulation. Proc. Natl. Acad. Sci. USA 102(44):15845-50.
  • Wu, J. and Lingrel, J.B. (2005) Kruppel-like factor 2, a novel immediate-early transcriptional factor, regulates IL-2 expression in T lymphocyte activation. J. Immunol. 175(5):3060-6.
  • Wu, J., Srinivasan, S.V., Neumann, J.C. and Lingrel, J.B. (2005) The KLF2 transcription factor does not affect the formation of preadipocytes but inhibits their differentiation into adipocytes. Biochemistry 44(33):11098-105.
  • Ahmad, N. and Lingrel, J.B. (2005) Kruppel-like factor 2 transcriptional regulation involves heterogeneous nuclear ribonucleoproteins and acetyltransferases. Biochemistry 44(16):6276-85.
  • Huddleson, J.P., Ahmad, N., Srinivasan, S. and Lingrel, J.B. (2005) Induction of KLF2 by fluid shear stress requires a novel promoter element activated by a phosphatidylinositol 3-kinase-dependent chromatin-remodeling pathway. J. Biol. Chem. 280(24):23371-9.
  • Looney, M.R., Sartori, C., Chakraborty, S., James, P.F. and Lingrel, J.B. (2005) Decreased expression of both the alpha1- and alpha2-subunits of the Na-K-ATPase reduces maximal alveolar epithelial fluid clearance. Am. J. Physiol. Lung Cell. Mol. Physiol. 289(1):L104-10.
  • Moseley, A.E., Huddleson, J.P., Bohanan, C.S., James, P.F., Lorenz, J.N, Aronow, B.J. and Lingrel, J.B. (2005) Genetic profiling reveals global changes in multiple biological pathways in the hearts of Na,K-ATPase alpha 1 isoform haploinsufficient mice. Cell Physiol. Biochem. 15:145-58.
  • Moseley, A.E., Cougnon, M.H., Grupp, I.L., El Schultz, J. and Lingrel, J.B. (2004) Attenuation of cardiac contractility in Na,K-ATPase alpha1 isoform-deficient hearts under reduced calcium conditions. J. Mol. Cell. Cardiol. 37(5):913-9.
  • Dostanic, I., Schultz, Jel J., Lorenz, J.N. and Lingrel, J.B. (2004) The alpha 1 isoform of Na,K-ATPase regulates cardiac contractility and functionally interacts and co-localizes with the Na/Ca exchanger in heart. J. Biol. Chem. 279(52):54053-61.
  • Dostanic, I., Paul, R.J., Lorenz, J.N., Theriault, S., Van Huysse, J.W. and Lingrel, J.B. (2004) The alpha2-isoform of Na-K-ATPase mediates ouabain-induced hypertension in mice and increased vascular contractility in vitro. Am J Physiol Heart Circ Physiol 2005 288(2):H477-85. Epub 2004 Sep 30.
  • Huddleson, J.P., Srinivasan, S., Ahmad, N. and Lingrel, J.B. (2004) Fluid shear stress induces endothelial KLF2 gene expression through a defined promoter region. Biol Chem 385(8):723-9.
  • Wu, J. and Lingrel, J.B. (2004) KLF2 inhibits Jurkat T leukemia cell growth via upregulation of cyclin-dependent kinase inhibitor p21WAF1/CIP1. Oncogene 23(49):8088-96.

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