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2014: Sarah Howles

I developed an interest in scientific research whilst studying medicine at Queens’ College, Cambridge and Brasenose College, Oxford. Following graduation in 2005, I began the training pathway to become a urological surgeon whilst seeking opportunities for involvement in both laboratory and clinically based academic studies.

As a urology trainee, I was struck by how common and debilitating recurrent kidney stone disease can be. However, our understanding of the pathology underlying this condition is relatively poor. I therefore joined Professor Thakker’s Academic Endocrine Unit as a Wellcome Trust Clinical Training Fellow to undertake a DPhil studying monogenetic causes of disorders of calcium homeostasis with the aim of increasing understanding of the mechanisms controlling calcium excretion.

These studies of the calcium-sensing receptor signalling pathway have demonstrated that loss- and gain-of-function mutation in the G-protein subunit, Ga11, cause the disorders of familial hypocalciuric hypercalcaemia type 2 and autosomal dominant hypocalcaemia type 2, respectively, whilst loss-of-function mutations in the adaptor protein 2 sigma subunit result in familial hypocalciuric hypercalcaemia type 3. The results of this work have been published in The New England Journal of Medicine and Nature Genetics. In addition to these investigations based on the study of molecular genetics, I have also 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 hope that I will be able to explore this further as a post-doctoral researcher.

I feel enormously privileged to have been able to study in such a stimulating, challenging and enjoyable environment. The skills and knowledge I have gained during this period of research have provided me with a platform from which to develop further research and my experiences within the Radcliffe Department of Medicine have given me confidence to pursue a career as an academic urologist.

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