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Deciphering mechanisms of acid-base balance in collecting duct intercalating cells

Dr. Emmanuelle Cordat
University of Alberta
Biomedical Research Grants
2017 - 2019
$100,000
Water, salt and calcium handling by the kidney
Distal renal tubular acidosis (dRTA) is a kidney disease that causes metabolic acidosis, difficulties to thrive in children, recurrent kidney stones and can ultimately lead to renal failure. dRTA is due to a malfunction of intercalated cells (ICCs) in the collecting duct, a specialized cell type that excretes the excess of protons we produce to the urine while reabsorbing the physiological buffer bicarbonate into the blood. dRTA can be caused by hereditary mutations in the gene encoding the bicarbonate transporter called Anion Exchanger 1 (kAE1). However, within the same cells, another bicarbonate transporter, SLC26A7, is present but it is unclear why this protein cannot compensate the lack of function of kAE1 in dRTA.

Our previous results showed that in dRTA conditions, SLC26A7 is down-regulated by an unknown mechanism. In this project, we will dissect the mechanisms that down-regulate the SLC26A7 transporter, with the aim of identifying pharmacological ways to manipulate its function to restore bicarbonate reabsorption in dRTA patients with a mutated anion exchanger 1. Understanding these mechanisms is not only relevant to dRTA patients but also to the growing cohort of Canadian patients with chronic kidney disease who have symptoms similar to those of dRTA patients.

Biography
Dr. Emmanuelle Cordat is an Associate Professor in the Department of Physiology at the University of Alberta, Edmonton. She joined the University as an Assistant Professor in 2007 after completing a six year-postdoctoral training at the University of Toronto under the supervision of Dr. Reinhart Reithmeier. Her undergraduate training was completed at the University of Nice/Sophia-Antipolis (France), where she also obtained her Ph.D. in Cellular and Molecular Pharmacology. Her research focuses on the physiology and pathophysiology of the collecting duct and more specifically how cells in this nephron segment regulate pH and electrolyte homeostasis. Abnormal pH homeostasis is a hallmark of chronic kidney disease, which affects millions of Canadians every year. Our laboratory is working towards a better understanding of the role of this nephron segment in maintaining a normal plasma pH and electrolyte composition.