Todd Alexander (PhD, Hospital for Sick Children, U of Toronto - MD, University of Western Ontario)

Associate Professor                                                                   Todd Alexander

Division of Nephrology
Departments of Pediatrics & Physiology
Faculty of Medicine & Dentistry
4-585 Edmonton Clinic Health Academy (ECHA)
11405-87 Avenue
Edmonton, Alberta T6G 1C9
Canada

Tel: 780 248-5557

todd2@ualberta.ca


Research Description

The focus of Dr. Alexander’s research is primary transport mechanisms by which the renal tubule regulates the body’s electrolyte and fluid balance. In particular he seeks to understand how altered tubular calcium transport leads to the development of osteoporosis and kidney stones and the molecular mechanisms underlying the increased renal sodium absorption which results in hypertension. More specifically, the lab is trying to identify the mechanisms both driving and permitting the paracellular flux of calcium between proximal tubular epithelia, the nephron segment recently identified to be defective in individuals with hypercalciuria, kidney stones and some individuals with osteoporosis. With respect to hypertension again the focus is the proximal nephron. However, in this instance a series of membrane protein-protein interactions are being analyzed to ascertain how the huge amount of salt (1.2 Kg per diem) and water (110L per diem) are absorbed in excess by this part of the kidney. The direct consequence of altered regulation in this process are volume expansion and increased blood pressure.


Selected publications

Increased water flux induced by an aquaporin-1/carbonic anhydrase II interaction. Vilas G, Krishnan D, Loganathan SK, Malhotra D, Liu L, Beggs MR, Gena P, Calamita G, Jung M, Zimmermann R, Tamma G, Casey JR, Alexander RT.   Mol Biol Cell. 2015 Mar 15;26(6):1106-18. doi: 10.1091/mbc.E14-03-0812. Epub 2015 Jan 21.  PMID: 25609088

Paracellular calcium transport across renal and intestinal epithelia. Alexander RT, Rievaj J, Dimke H.   Biochem Cell Biol. 2014 Dec;92(6):467-80. doi: 10.1139/bcb-2014-0061. Epub 2014 Sep 17.   PMID:25386841

Traditional and emerging roles for the SLC9 Na+/H+ exchangers. Fuster DG, Alexander RT.  Pflugers Arch. 2014 Jan;466(1):61-76. doi:   10.1007/s00424-013-1408-8. Epub 2013 Dec 12. Review.  PMID: 24337822

Kidney stones and cardiovascular events: a cohort study. Alexander RT, Hemmelgarn BR, Wiebe N, Bello A, Samuel S, Klarenbach SW, Curhan GC, Tonelli M; Alberta Kidney Disease Network.  Clin J Am Soc Nephrol. 2014 Mar;9(3):506-12. doi: 10.2215/CJN.04960513. Epub 2013 Dec 5.   PMID: 24311706

The Na⁺/H⁺ exchanger isoform 3 is required for active paracellular and transcellular Ca²⁺ transport across murine cecum. Rievaj J, Pan W, Cordat E, Alexander RT. Am J Physiol Gastrointest Liver Physiol. 2013 Aug 15;305(4):G303-13. doi: 10.1152/ajpgi.00490.2012. Epub 2013 Jun 13. PMID:23764894 [PubMed - indexed for MEDLINE]

Proximal tubular NHEs: sodium, protons and calcium? Alexander RT, Dimke H, Cordat E. Am J Physiol Renal Physiol. 2013 Aug 1;305(3):F229-36. doi: 10.1152/ajprenal.00065.2013. Epub 2013 Jun 12. Review. PMID:23761670 [PubMed - indexed for MEDLINE]

Activation of the Ca(2+)-sensing receptor increases renal claudin-14 expression and urinary Ca(2+) excretion. Dimke H, Desai P, Borovac J, Lau A, Pan W, Alexander RT. Am J Physiol Renal Physiol. 2013 Mar 15;304(6):F761-9. doi: 10.1152/ajprenal.00263.2012. Epub 2013 Jan 2. PMID: 23283989 [PubMed - indexed for MEDLINE]

Ezrin is required for the functional regulation of the epithelial sodium proton exchanger, NHE3. Hayashi H, Tamura A, Krishnan D, Tsukita S, Suzuki Y, Kocinsky HS, Aronson PS, Orlowski J, Grinstein S, Alexander RT. PLoS One. 2013;8(2):e55623. doi: 10.1371/journal.pone.0055623. Epub 2013 Feb 6. PMID:23405179 [PubMed - indexed for MEDLINE]

The epithelial sodium/proton exchanger, NHE3, is necessary for renal and intestinal calcium (re)absorption. Pan W, Borovac J, Spicer Z, Hoenderop JG, Bindels RJ, Shull GE, Doschak MR, Cordat E, Alexander RT. Am J Physiol Renal Physiol. 2012 Apr 15;302(8):F943-56. doi: 10.1152/ajprenal.00504.2010. Epub 2011 Sep 21. PMID: 21937605 [PubMed - indexed for MEDLINE]

Claudin-4 forms a paracellular barrier, revealing the interdependence of claudin expression in the loose epithelial cell culture model opossum kidney cells. Borovac J, Barker RS, Rievaj J, Rasmussen A, Pan W, Wevrick R, Alexander RT. Am J Physiol Cell Physiol. 2012 Dec;303(12):C1278-91. doi: 10.1152/ajpcell.00434.2011. Epub 2012 Oct 17.PMID: 23076790 [PubMed - in process]

Kidney stones and kidney function loss: a cohort study. Alexander RT, Hemmelgarn BR, Wiebe N, Bello A, Morgan C, Samuel S, Klarenbach SW, Curhan GC, Tonelli M; Alberta Kidney Disease Network. BMJ. 2012 Aug 29;345:e5287. doi: 10.1136/bmj.e5287. PMID: 22936784 [PubMed - indexed for MEDLINE]  

Survival and transplantation outcomes of children less than 2 years of age with end-stage renal disease. Alexander RT, Foster BJ, Tonelli MA, Soo A, Nettel-Aguirre A, Hemmelgarn BR, Samuel SM; of the Pediatric Renal Outcomes Group Canada. Pediatr Nephrol. 2012 Oct;27(10):1975-83. doi: 10.1007/s00467-012-2195-8. Epub 2012 Jun 7.PMID: 22673972

The calmodulin antagonist W-7 inhibits the epithelial Na+/H+ exchanger via modulating membrane surface potential. Jaumouillé V, Krishnan D, Alexander RT. Channels (Austin). 2011 Jul-Aug;5(4):308-13. doi: 10.4161/chan.5.4.16548. Epub 2011 Jul 1. PMID: 21654199

Membrane surface charge dictates the structure and function of the epithelial Na+/H+ exchanger. Alexander RT, Jaumouillé V, Yeung T, Furuya W, Peltekova I, Boucher A, Zasloff M, Orlowski J, Grinstein S. EMBO J. 2011 Feb 16;30(4):679-91. doi: 10.1038/emboj.2010.356. Epub 2011 Jan 18. PMID: 21245831


Claudin-4 forms a paracellular barrier, revealing the interdependence of claudin expression in the loose epithelial cell culture model opossum kidney cells. Borovac J, Barker RS, Rievaj J, Rasmussen A, Pan W, Wevrick R, Alexander RTAm J Physiol Cell Physiol. 2012 Dec;303(12):C1278-91. doi: 10.1152/ajpcell.00434.2011. Epub 2012 Oct 17.PMID: 23076790 [PubMed - in process]


and


Kidney stones and kidney function loss: a cohort study. Alexander RT, Hemmelgarn BR, Wiebe N, Bello A, Morgan C, Samuel S, Klarenbach SW, Curhan GC, Tonelli M; Alberta Kidney Disease Network. BMJ. 2012 Aug 29;345:e5287. doi: 10.1136/bmj.e5287. PMID: 

22936784 [PubMed - indexed for MEDLINE] 



and change the top citation to:


The epithelial sodium/proton exchanger, NHE3, is necessary for renal and intestinal calcium (re)absorption. Pan W, Borovac J, Spicer Z, Hoenderop JG, Bindels RJ, Shull GE, Doschak MR, Cordat E, Alexander RTAm J Physiol Renal Physiol. 2012 Apr 15;302(8):F943-56. doi: 10.1152/ajprenal.00504.2010. Epub 2011 Sep 21. PMID: 21937605 [PubMed - indexed for MEDLINE]