Todd Alexander (PhD, Hospital for Sick Children, University of Toronto)

Professor

Department of Pediatrics and Physiology
4-555 Edmonton Clinic Health Academy
11405 - 87 Avenue
Phone: (780) 248-1493
Fax: (780) 492-0450

Todd.Alexander@albertahealthservices.ca

Lab Website

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

Alexander R.T., Cordat E., Chambrey R., Dimke H., Eladari D. (2016) - "Acidosis and urinary calcium excretion, insights from genetic disorders". In press for Journal of the American Society of Nephrology.

Krishnan D, Liu L, Wiebe SA, Casey JR, Cordat E, Alexander RT. (2015) Carbonic anhydrase II binds to and increases the activity of the epithelial sodium-proton exchanger, NHE3. Am J Physiol Renal Physiol. 309(4):F383-92.

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. (2015) Increased water flux induced by an aquaporin-1/carbonic anhydrase II interaction.. Mol Biol Cell. Mar 15;26(6):1106-18.

Alexander RT, Beggs MR, Zamani R, Marcussen N, Frische S, Dimke H. (2015) Ultrastructural and Immunohistochemical Localization of the Plasma Membrane Ca2+-ATPase 4 (PMCA4) in Ca2+-Transporting Epithelia. Am J Physiol Renal Physiol. Jul 15:ajprenal.00651.2014. doi: 10.1152/ajprenal.00651.2014.

Alexander RT, Hemmelgarn BR, Wiebe N, Bello A, Samuel S, Klarenbach SW, Curhan GC, Tonelli M. (2014) for the Alberta Kidney Disease Network. Kidney stones and cardiovascular events: a cohort study. Clin J Am Soc NephrolMar;9(3):506-12.

Fuster DG and Alexander RT. (2014) Traditional and Emerging Roles of the SLC9 Na⁺/H⁺ exchangers. Pflugers Arch Jan;466(1):61-76.

Dimke H, Desai P, Borovac J, Lau A, Pan W, Alexander RT. (2013) Activation of the Ca²⁺-Sensing Receptor Increases Renal Claudin-14 Expression and Urinary Ca²⁺ Excretion. Am J Physiol Renal Physiol Mar 15;304(6):F761-9.

Alexander RT, Dimke H, Cordat E. (2013) Proximal Tubular NHEs: Sodium, Protons and Calcium? Am J Physiol Renal Physiol Aug;305(3):F229-36.

Rievag J, Pan W, Cordat E, Alexander RT. (2013) The Na⁺/H⁺ Exchanger Isoform 3 is required for active paracellular and transcellular Ca²⁺ transport across murine caecum. Am J Physiol Gastrointest Liver Physiol Aug;305(4):G303-13.

Pan W, Borovac J, Spicer Z, Hoenderop JG, Bindels RJ, Shull GE, Doschak MR, Cordat E, Alexander RT. (2012) The Epithelial Sodium Proton Exchanger, NHE3, is necessary for renal and intestinal calcium (re)absorption. Am J Physiol Renal Physiol, 2(8):F943-56. (I am senior and corresponding Author).

Samuel SM, Foster BJ, Tonelli MA, Nettel-Aguirre A, Soo A, Alexander RT, Hemmelgarn BR; (2012) Association between distance from renal care center and death in pediatric end-stage renal disease patients. Pediatr Transplant Nov;16(7):735-41.

Alexander RT, Foster BJ, Tonelli MA, Soo A, Nettel-Aguirre A, Hemmelgarn BR and Samuel SM; (2012) the Pediatric Renal Outcomes Canada Group. Outcomes of Children Less than 2 years of Age initiating dialysis. Pediatr Nephrol. Oct;27(10):1975-83.

Almomani EY, King JC, Netsawang J, Yenchitsomanus PT, Malasit P, Limjindaporn T, Alexander RT, Cordat E. (2012) Adaptor protein 1 complexes regulate intracellular trafficking of the kidney anion exchanger 1 in epithelial cells. Am J Physiol Cell Physiol. Sep;303(5):C554-66.

Samuel SM, Foster BJ, Hemmelgarn BR, Nettel-Aguirre A, Crowshoe L, Alexander RT, Soo A, Tonelli MA. (2012) Incidence and causes of end-stage renal disease among Aboriginal children and young adults. CMAJ. Oct 2;184(14):E758-64.

Borovac J, Barker RS, Rasmussen A, Pan W, Wevrick R and Alexander RT. (2012) Claudin-4 forms a paracellular barrier, revealing the interdependence of claudin expression in the loose epithelial cell culture model opossum kidney cells. Am J Physiol Renal Physiol, Dec;303(12):C1278-91. (I am Corresponding Author).

Alexander RT, Jaumouillé V, Yeung T, Furuya W, Peltekova I, Boucher A, Zasloff M, Orlowski J, Grinstein S.EMBO J. (2011) Membrane surface charge dictates the structure and function of the epithelial Na⁺/H⁺ exchanger. 30(4):679-91.