John Orlowski
Professor, Department of Physiology
B.Sc., McGill, M.Sc., Ph.D., Queen's
The scientific interests of my laboratory are directed towards developing a comprehensive understanding of the dynamics of cellular acid-base (pH) homeostasis as it pertains to human health and disease, with a focus on one major component of the cellular pH-regulatory machinery, namely alkali cation [Na+, K+, Li+]/proton (H+) exchangers, commonly referred to as Na+/H+ exchangers (NHEs) (i.e., members of the solute carrier SLC9 gene family). These transporters play direct roles in controlling not only cellular pH and volume, but also contribute to a host of other physiological processes such as cellular adhesion, migration, proliferation, transformation and apoptosis. Disruptions in the normal function of certain NHEs have been linked to the progression of a number of human diseases, including hypertension, cardiac arrhythmias and failure, stroke, congenital secretory diarrhea, diabetes, and certain neurological disorders (e.g., Lichtenstein-Knorr Syndrome, Christianson Syndrome, epilepsy, autism, attention deficit hyperactivity disorder).
Previous work by my laboratory resulted in the identification and molecular cloning of several novel members of the mammalian NHE/SLC9 gene family. My current research uses a range of molecular, cellular and physiological techniques to address several distinct aspects of NHE biology, including the following aims: (1) to define the transmembrane organization and structural domains of the exchanger responsible for cation translocation and drug recognition in order to develop a molecular model that accounts for the functional dynamics of this transporter; (2) to define the protein sorting and signalling mechanisms that underlie the membrane targeting and regulation of the NHEs; (3) to evaluate the physiological and pathophysiological contributions of certain NHEs to cell function, health and disease.