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Biography

I am a researcher and trainee in urological surgery. My research is based in the Oxford Centre for Diabetes, Endocrinology and Metabolism, Churchill Hospital, where I work as part of Professor Rajesh Thakker’s group. I studied medicine at Cambridge and Oxford Universities between 1999 and 2005 and since qualification have worked in the Oxford region, entering the Urology training scheme in 2010. I was appointed as a Wellcome Trust clinical training fellow in 2011 and as an NIHR Academic Clinical Lecturer in Urology in 2015. 

Sarah Howles

DPhil, MRCS (Eng), MA (Cantab)

Academic Clinical Lecturer in Urology

Kidney stone disease is a common problem, affecting up to 20% of men and 10% of women by 70 years of age. Hypercalciuria is linked to an increased risk of forming such stones and my research focuses on trying to understand the tubular process regulating calcium excretion. My approach is to study monogenetic disorders causing either hypercalcaemia or hypercalciuria and identify the molecular pathways resulting in this phenotype.

So far, my work has focused on disorders of the calcium sensing receptor (CaSR) signalling pathway. Loss-of-function mutations of the calcium sensing receptor (CaSR) cause familial hypocalciuric hypercalcaemia type 1 (FHH1), whilst gain-of-function mutations are associated with autosomal dominant hypocalcaemia (ADH). However, 35% of cases of FHH and 60% of cases of ADH are not due to CaSR mutations. My studies have demonstrated that FHH type 2 (FHH2) and the new clinical disorder, ADH type 2 (ADH2), are due to loss- and gain-of-function mutations in the G-protein subunit, Gα11, respectively; a protein through which the CaSR signals. I have also demonstrated that FHH3 is due to loss-of-function mutations in the adaptor protein 2 sigma subunit, AP2σ2, likely due to impaired CaSR endocytosis. Furthermore, I have demonstrated that these signalling defects can be rectified by the use of the CaSR allosteric modulator cinacalcet. These studies have facilitated improved molecular diagnosis of FHH and ADH and enabled better treatment of FHH3.

In addition I have developed a hypothesis regarding the foetal origins of kidney stone disease. This hypothesis has been published in the Journal of Bone and Mineral Research and I plan to explore this further as a post-doctoral researcher.

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Recent Publications

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