Congratulations to Jonathan Whittamore, PhD, of the Experimental Pathology Division

Published: March 21st, 2018

Category: Department News, Pathology News

Congratulations to Jonathan Whittamore, PhD, of the Experimental Pathology Division. He has recently received a research grant from the Oxalosis Hyperoxaluria Foundation. This award, entitled “The sulphate transporter SAT-1(SLC26a1) is essential for oxalate clearance from the liver in Primary Hyperoxaluria Type 1”  and provides $200,000 of support for two years.

The vast majority of oxalate eliminated in the urine originates from liver metabolism. Hyperoxaluria (elevated urine oxalate) is a major risk factor for kidney stone formation, one of the most common forms of kidney disease for which treatment options are limited. While dietary sources of oxalate can be restricted, this cannot offset the continuous metabolic over-production by the Primary Hyperoxalurias (PHs), a group of rare inherited diseases caused by liver enzyme deficiencies. Of the three described forms, PH type 1 is the most frequently encountered and severe, resulting in recurrent kidney stone formation with progressive renal failure accompanied by widespread oxalate deposition in other organs (oxalosis), a further life-threatening complication. There has been considerable investment in understanding the metabolic pathways related to the PHs for the benefit of emerging and future treatment/curative options targeting the liver.

Remarkably, there is one critical aspect that has so far been completely overlooked – how the metabolic end-product oxalate is actually transported out of the liver into the blood. This is surprising considering the liver is the source of the overwhelming oxalate burden in PH1 patients and, incredibly, it is the one organ to not be afflicted by oxalosis. This means the cells of the liver possess an extremely efficient mechanism for eliminating oxalate, although this has not been systematically examined. The current model of liver oxalate transport is based on a very limited number of studies implicating a major role for a protein called SAT-1 (Sulfate Anion Transporter 1). It has been hypothesized that SAT-1 is upregulated in the PH1 liver but this notion remains untested. The goal of this proposal is to undertake the first systematic characterization of oxalate transport by the liver and formally test this hypothesis. This work is essential to a complete understanding of oxalate metabolism in PH1 and other forms of hyperoxaluria. Such basic information may prove beneficial for research into emerging and future treatment strategies, specifically those targeting the liver.