John Orlowski, Chair

Research Area:  Cell and Molecular Biology

Research Description:

The research interests of my laboratory are to better understand the molecular mechanisms underlying pH homeostasis of mammalian cells, focusing on a certain family of transporters called sodium/proton exchangers.  In addition to regulating cytoplasmic and organellar pH, they play an important role in the maintenance of cell volume and the (re)absorption of sodium across intestinal and renal epithelial cells.  Abnormal expression of some of these transporters has been implicated in the pathogenesis of certain human diseases, including essential hypertension, congenital secretory diarrhea, and injuries resulting from episodes of cardiac ischemia and reperfusion

Education:  B.Sc., McGill, M.Sc., Ph.D., Queen's

Recent Publications:

Zaun, H.C., Shrier, A. and Orlowski, J. (2008) Calcineurin B-Homologous Protein 3 Promotes the Biosynthetic Maturation, Cell Surface Stability and Optimal Transport of the Na+/H+ Exchanger NHE1 Isoform.   J. Biol. Chem. 283(18):12456-67

Orlowski, J. and Grinstein, S. (2007) Emerging Roles of Alkali Cation/Proton Exchangers in Organellar Homeostasis.  Current Opinion in Cell Biology 19(4):483-92.

Alexander, R.T., Malevanets, A., Durkan, A.M., Kocinsky, H.S., Aronson, P.S., Orlowski, J. and Grinstein S. (2007) Membrane curvature alters the activation kinetics of the epithelial Na+/H+ exchanger NHE3.  J. Biol. Chem. 282(10):7376-84. 

Alexander, R.T., Furuya, W., Szaszi, K., Orlowski, J., and Grinstein, S. (2005) Rho GTPases dictate the mobility of the Na+/H+ exchanger NHE3 in epithelia. Role in apical retention and targeting.  Proc. Natl. Acad. Sci. USA 102(34): 12253-12258. 

Kocinsky, H.S., Girardi, A.C.C., Biemesderfer, D., Nguyen, T., Mentone, S.A., Orlowski, J., and Aronson, P.S. (2005) Use of phosphospecific antibodies to determine the phosphorylation of endogenous Na+/H+ exchanger NHE3 at PKA consensus sites.  Am. J. Physiol. Renal Physiol. 289: F249-F258.

 Lin, P. J. C., Williams, W. P., Luu, Y., Molday, R. S., Orlowski, J. and Numata, M. (2005) Secretory carrier membrane proteins interact and regulate trafficking of the organellar (Na+,K+)/H+ exchanger NHE7.  J. Cell Sci. 118: 1885-1897. 

Szabó, E.Z., Numata, M., Lukashova, V., Iannuzzi, P. and Orlowski, J. (2005) b-Arrestins bind and decrease cell-surface abundance of the Na+/H+ exchanger NHE5 isoform.  Proc. Natl. Acad. Sci. USA 102(8): 2790-2795.

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