Prof. Larry Fliegel

powered by
COS Expertise®
University of Alberta
Medicine and Dentistry
Biochemistry
ProfessorAppointed: 1989
University of Alberta
Medicine and Dentistry
Biochemistry
ProfessorAppointed: 1989
Professional Headshot of Larry Fliegel

Mailing Address

347 Medical Science Bldg.
University of Alberta
Dept of BIochemistry
Edmonton, Alberta T6G 2H7
Canada

Contact Information

Phone: (780) 492-1848
Fax: (780) 492-0886
lfliegel@ualberta.ca
http://www.biochem.ualberta.ca/Biochem/Faculty/Fliegel/Flieg

Qualifications

Ph.D., University of Calgary, Medical Science, 1984.
M.Sc., University of Manitoba, 1980.

Expertise and Research Interests

Handling acid is a problem in all organisms. As a result of metabolism, excess intracellular acid is produced in all cells. Too much acid has a deleterious effect on the activity of various enzymes and results in abnormalities in metabolism and cell cycle. In the heart, too much acid inhibits contractile activity and damages the myocardium. Our laboratory studies the regulation of intracellular pH and the removal of excess intracellular acid. In mammalian tissues the main protein responsible for this is the Na+/H+ exchanger. The Na+/H+ exchanger is a mammalian plasma membrane protein that exchanges one intracellular proton for an extracellular sodium. It is involved in pH regulation and is stimulated by growth factors.
My laboratory has studied many aspects of this protein. The Na+/H+ exchanger has two general domains, a membrane domain that pumps ions and an inside, cytoplasmic tail. We have studied the structure and function of both domains. This includes studies using site specific mutagenesis of amino acids and studies on regulatory protein binding.
We have also studied regulation of the Na+/H+ exchanger by protein kinases and we also examined which other regulatory proteins control expression of the Na+/H+ exchanger during development.
A third study used yeast to model the Na+/H+ exchanger. We can more easily manipulate the yeast form of this protein. The yeast protein is involved in salt tolerance in plants and E. coli.
The laboratory continues to be involved in new and exciting studies on regulation of activity and expression of Na+/H+ exchange proteins. Many new projects are underway and are waiting to be developed.

Other Expertise

Academic Experience:Protein purification;polyclonal antibody production; DNA sequencing using PEMBL, M13 and pentylene tetrazote (PTZ), bluescript;cDNA library screening with synthetic oligonucleotide probes;experience in expression library construction and screening;expression of cDNA in mammalian cells and in Escherichia coli;isolation and analysis of genomic DNA;isolation of intact eukaryotic messenger (mRNA);Northern and Southern analysis;restriction mapping and related gel techniques;Western blot analysis;Two Hybrid Screening

Future Research

In the future, we are interested in research in many areas. This includes structural analysis of the Na/H exchanger and its role in embryonic stem cell differentiation.

Industrial Relevance

Plan Na/H exchangers are used to extrude excess salt. This is important in drought resistance. The mammalian Na/H exchanger is involved in ischemic damage to the heart that occurs in heart disease. It is a subject of intense investigation for clinical use.

Keywords

COS Keywords:

Biochemistry, Biological Sciences, Cell Cloning, Complementary DNA, Deoxyribonucleic Acid, Molecular Biology.

Additional Terms:

CDNA, Clone, Complementary DNA, Deoxyribonucleic Acid, Hydrogen Ion, Ion Exchanger, Ion Transport, MDNA, Messenger DNA, Molecular Biology, Myocardium, Na+/H+ Antiport, Sarcolemma, Sodium Ion, Yeast.

Languages

(Reading, Writing, Speaking)

English

Memberships

American Association for the Advancement of Science
Biophysical Society
FASEB
International Society for Heart Research

Honors and Awards

2007-2008, McCalla Research Professor, Department of Biochemistry, University of Alberta
2007-2012, Heritage Foundation for Medical Research Scientist, Alberta Heritage Foundation for Medical Research (AHFMR), University of Alberta

Previous Positions

1987-1989, University of Alberta, Postdoctoral Fellow
1984-1987, University of Toronto, Postdoctoral Fellow

Funding Received

  • Medical Research Council (MRC) - Canada: CIHR, The Na+/H+ exchanger and heart hypertrophy, $104,000, 2004 to 2009.
  • Medical Research Council (MRC) - Canada: Molecular analysis of the NHE1 isoform of the Na+/H+ exchanger, $79,000, 2004 to 2009.
  • Canadian Institutes of Health Research (CIHR): Regulation of the Na+/H+ exchanger in the mammalian myocardium., $94,000, 2004 to 2009.
  • Natural Sciences and Engineering Research Council of Canada (NSERC): Molecular analysis of a salt tolerance protein in yeast., $30,000, 2003 to 2008.

Publications

  • Ding, Jie, J.K. Rainey, Xu, C., Sykes, B.D. and L. Fliegel (2006) Structural and functional characterization of TM VII of the NHE1 isoform of the Na+/H+ exchanger., J. Biol. Chem., 281, 29817-29829
  • Karmazyn M, Sawyer M, Fliegel L (Aug 2005) The Na(+)/H(+) exchanger: a target for cardiac therapeutic intervention., Current Drug Targets. Cardiovascular & Haematological Disorders, 5 (4), 323-35 Abstract
  • Slepkov ER, Rainey JK, Li X, Liu Y, Cheng FJ, Lindhout DA, Sykes BD, Fliegel L (May 2005) Structural and functional characterization of transmembrane segment IV of the NHE1 isoform of the Na+/H+ exchanger., The Journal of Biological Chemistry, 280 (18), 17863-72 Abstract
  • Misik AJ, Perreault K, Holmes CF, Fliegel L (Apr 2005) Protein phosphatase regulation of Na+/H+ exchanger isoform I., Biochemistry, 44 (15), 5842-52 Abstract
  • Emily R. Slepkov, Jan K. Rainey, Xiuju Li, Yongsheng Liu, Darrin A. Lindhout, Brian D. Sykes and Larry Fliegel (2005) Structural and functional characterization of transmembrane segment IV of the NHE1 isoform of the Na+/H+ exchanger., J. Biological Chemistry, 280, 17863-17872
  • M. Karmazyn, Q. Liu, X. T. Gan, B.J. Brix, L. Fliegel, Aldosterone increases Na+-H+ exchange 1 (NHE-1) expression and induces NHE-1 dependent hypertrophy in cultured neonatal rat ventricular myocytes, Hypertension, 42(6), 1171-1176, 2003
  • A. Moor, Xiaohong Tracey Gan, Morris Karmazyn, Larry Fliegel, Activation of Na+/H+ exchanger-directed protein kinases in the ischemic and ischemic-reperfused rat myocardium, Journal of Biological Chemistry, 276, 16113-16122, 2001
  • Rakhilya Murtazina, Brenda J. Booth, Bonnie L. Bullis, Dyal N. Singh, L. Fliegel, Functional Analysis of Polar Amino Acid Residues in Membrane Associated Regions of the NHE1 Isoform of the Na+/H+ Exchanger, European Journal of Biochemistry, 268, 1-13, 2001
  • A. N. Moor, L. Fliegel, Protein Kinase Mediated Regulation of the Na+/H+ Exchanger in the Rat Myocardium by MAP-Kinase-dependent Pathways, Journal of Biological Chemistry, 274, 22985-22992, 1999
  • W. Yang. H. Wang and L. Fliegel (1996) Role of a Poly T rich region in Regulation of Expression of the NHE1 Promoter. J. Biol. Chem. 271:20444-20449
  • W. Yang, J.R.B. Dyck, H. Wang and L. Fliegel. (1996) Regulation of the NHE-1 promoter in the mammalian myocardium. Am. J. Physiol. 270:H259-H266
  • J.R.B. Dyck and L. Fliegel (1995) Specific Activation of the Na+/H+ Exchanger Gene During Neuronal Differentiation of Embryonal Carcinoma Cells. J. Biol. Chem. 270:10420-10427
  • Dyck, J.R.B., Norma L.C.L. Silva and L. Fliegel. (1995) Activation of the Na+/H+ exchanger promoter by the transcription factor AP-2. J. Biol. Chem. 270:1375-1381

Profile Details

Last Verified: 3/6/2007

COS Expertise ID #219409
Reference this profile directly: http://myprofile.cos.com/fliegell09