WOMEN IN CANCER PROFILE: From bedside to bench and back: my journey in thyroid disease

in Endocrine-Related Cancer
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  • 1 Reader in Endocrinology, Institute of Metabolism and Systems Research, College of Medical and Dental Sciences, University of Birmingham, Birmingham, UK
  • 2 Centre for Endocrinology, Diabetes and Metabolism, Birmingham Health Partners, Birmingham, UK

I am the oldest of three girls in a Belgian family. I was born in the USA in 1970, whilst my parents were studying at the University of Wisconsin. Upon completion of their postgraduate studies, my parents returned to their native country Belgium when I was aged one. From a young age I was fascinated by medicine and in secondary school, human biology was my favourite subject. Whilst neither of my parents is medically trained, they always encouraged me and my sisters to have an inquisitive spirit and fuelled a thirst for knowledge and discovery. Following completion of my secondary school studies in 1988, I entered medical school at the Catholic University in Leuven, Belgium, to fulfil my aspiration of becoming a doctor.

The medical course in Belgium in those days encompassed 3 years of pre-clinical and 4 years of clinical studies. Although I was thrilled to study subjects such as physiology, anatomy and biochemistry during the preclinical years, it was the study of pathology and diseases as well as the patient interaction during the clinical years of study, which affirmed my feeling that I had made the right career choice. In 1993, during my 6th year of study, I was given the unique opportunity of participating in an Erasmus exchange programme, which allowed me to complete a period of elective placements in Dublin, Ireland and in Kirkcaldy, Scotland, studying Obstetrics and Gynaecology and Paediatrics respectively. During my placement on the neonatal unit in Kirkcaldy, I befriended Bhaskar, a junior trainee in Paediatrics and fell in love. As I still had to complete about 18 months of training following my elective in Scotland, I returned to Belgium, maintaining a long-distance relationship through sporadic phone calls, occasional visits and regular letter writing. When I qualified as MD (Summa cum Laude) in 1995, I took up a house officer job in Medicine in Wolverhampton, UK, where Bhaskar was working at the time. We were married in 1996 and have remained around the West Midlands where we now live with our two children Nathan (aged 17) and Indu (aged 15).

During my training as a junior doctor at the Royal Wolverhampton NHS Trust, I developed a fondness for Endocrinology and Diabetes, fascinated by the complex, yet logical, control mechanisms involved in the regulation and secretion of hormones. I obtained Membership of Royal College of Physicians (MRCP) in 1998, whilst heavily pregnant with my son Nathan. During my maternity leave, I approached Professor Jayne Franklyn at the University of Birmingham to explore the possibility of participating in a research project to broaden my horizon in the field of Endocrinology. This was the start of my career in Academic Endocrinology and Jayne has remained my trusted mentor and friend over the last 16 years.

I was fortunate enough to obtain a Wellcome Trust Entry level fellowship in 2000, allowing me to conduct a 12-month research project to study the role of the pituitary tumour transforming gene (PTTG), a newly diagnosed proto-oncogene, in pituitary adenomas. I was introduced to my other mentor, Prof Chris McCabe, and under his and Jayne’s guidance, we established that PTTG and its binding factor PBF are overexpressed in pituitary tumours and that this is associated with overexpression of growth factors including fibroblast-growth factor-2 (FGF-2) and vascular endothelial growth factor (VEGF) (McCabe et al. 2002, 2003, Tannahill et al. 2002, Rabbitt et al. 2003). It soon became apparent that PTTG and PBF are involved in other endocrine tumours, and I identified that overexpression of PTTG and PBF are markers of prognosis in thyroid cancer, independent of patients’ age and gender and of tumour type and size (Boelaert et al. 2003a, Stratford et al. 2005). Subsequent studies in our group have confirmed overexpression in other endocrine-related neoplasia including colon (Read et al. 2016) and breast cancers (Boelaert & Franklyn 2003, Watkins et al. 2010). Further functional investigations have unravelled some of the mechanisms through which these genes signal indicating roles in the initiation (Kim et al. 2005) as well as the promotion of tumourigenesis through the upregulation of pro-mitogenic and pro-angiogenic growth factors (Kim et al. 2006a,b). I helped to identify the functional motifs within PTTG and PBF (Boelaert et al. 2004) and the role played by phosphorylation in the interaction of these proteins with others thereby governing a number of cellular processes (Smith et al. 2013).

After my entry-level fellowship and the birth of my daughter Indu in 2001, I successfully obtained a Wellcome Trust Clinical Training Fellowship to further investigate the pathogenesis of thyroid tumours. Detailed investigations determined that both PTTG and PBF repress the expression, localisation and function of the sodium iodide symporter (NIS), thereby crucially affecting treatment of thyroid tumours with radioiodine (Boelaert et al. 2007, Smith et al. 2009). PTTG was also identified as human securin, an important protein in normal mitosis, and additional investigations performed during my PhD studies elucidated a potential role for PTTG in human foetal brain development (Boelaert et al. 2003b, Pemberton et al. 2007). Overall, the findings obtained during my PhD studies have laid the foundations for a large collaborative programme of laboratory research investigating the pathogenesis of endocrine neoplasia and more recently the exploration of novel approaches into the re-engineering of radio-iodine for refractory thyroid cancer.

Having obtained my PhD in 2005, I went back into a period of clinical training as a Lecturer in Endocrinology at the University of Birmingham. This allowed me to establish a portfolio of translational research through the exploration of large, detailed and unique clinical databases. Notable findings include the identification of the concentration of serum TSH at diagnosis as an independent predictor of malignancy in patients with thyroid nodules, findings which were subsequently confirmed by various different researchers (Boelaert et al. 2006, Boelaert 2009). Moreover, I have conducted a number of clinical studies evaluating the diagnosis and management of patients with thyroid dysfunction (Boelaert & Franklyn 2005, Manji et al. 2006a,b, Franklyn & Boelaert 2012, Boelaert 2013, Chortis et al. 2014, Edmunds et al. 2015). Important studies have confirmed the lack of symptoms in elderly patients presenting with hyperthyroidism (Boelaert et al. 2010b, Boelaert 2013, Jones & Boelaert 2015), the associations between autoimmune thyroid disease and other autoimmune conditions (Boelaert et al. 2010a) and the demonstration of radioactive iodine as a safe and effective treatment in patients with hyperthyroidism (Boelaert et al. 2009, 2013).

After a period of specialist training in endocrinology in Birmingham, I successfully applied for an MRC Clinician Scientist Fellowship, which was awarded in 2007. This allowed a further dedicated period of laboratory research and also laid the foundations for me to start establishing my own independent research group. The studies performed during my post-doctoral work have generated and developed mouse models of thyroid tumourigenesis further detailing the molecular pathways activated in thyroid neoplasia by PTTG and PBF. Their crucial interactions with the sodium iodide symporter have identified potential new therapeutic targets in the treatment of thyroid cancer with radioiodine (Read et al. 2011, Smith et al. 2012, Lewy et al. 2013). We have set up a large programme of research to identify the maximal therapeutic strategy to enhance radioiodine therapy in pre-clinical models of thyroid cancer. We are aiming to acquire new scientific insights into the fundamental mechanisms of action of NIS in vivo, as pre-requisites to clinical trials, which are required to enhance radioiodine treatment for all patients with thyroid cancer and to address the poor 5-year survival of those patients who currently do not respond to 131-I treatment.

I have maintained a keen interest in collaborative clinical research including the evaluation of the efficacy of fine needle aspirations in patients with medullary thyroid cancer (Essig et al. 2013), contributions to a meta-analysis exploring recurrence and mortality in papillary thyroid micro-carcinomas (Mehanna et al. 2014) as well as the evaluation of metyrapone as an effective treatment in the management of Cushing’s syndrome (Daniel et al. 2015). I have been fortunate to have the opportunity to establish a team of clinical and scientifically trained researchers in continued collaboration with Chris McCabe. Working with these talented pre- and postdoctoral fellows and students has allowed me to adopt a true bench to bedside research approach into various aspects of thyroidology.

In addition to the laboratory and clinical research avenues described previously, my most recent endeavours extend further into translational patient-centred care. I am involved in a number of multi-centre clinical trials including the ELATION trial, which is exploring the efficacy of elastography in the diagnosis of malignancy in patients presenting with thyroid nodules. Moreover, I have developed a keen clinical interest in the management of endocrine disorders during pregnancy (Chan & Boelaert 2014, Brabant et al. 2015) and am taking part in the TABLET trial, which is exploring the efficacy of levothyroxine replacement in TPO antibody-positive euthyroid women during pregnancy. I have helped to determine the prevalence and economic consequences of mild-to-moderate iodine deficiency in the UK (Vanderpump et al. 2011, Monahan et al. 2015, Zimmermann & Boelaert 2015). Additionally, I work closely with a number of patient organisations and some of our studies have investigated the application of novel software to assess the readability of patient information leaflets for patients with thyroid disorders (Edmunds et al. 2014). These findings have been crucial in the editing of Revised UK Thyroid Cancer Guidelines, which I have co-authored (Perros et al. 2014).

Future research avenues which I hope to pursue include the continued exploration of novel ways to overcome radio-iodine-resistant thyroid cancer, the optimisation of management of thyroid dysfunction during pregnancy and the exploration of novel diagnostic and therapeutic approaches for patients with thyroid nodules. My aim is to deliver a varied portfolio of innovative research by adopting a true translational bench-to-bedside approach, by leading an impressive team of talented researchers and by working highly collaboratively within a network of national and international leaders in the field.

Through dedicated and committed guidance by my mentors, I have learned to appreciate the importance of training the next generation of researchers and clinicians. I continue to supervise a number of PhD students and have taken on leadership roles in nurturing the careers of budding clinical academics, locally, regionally and internationally. I take part in the setting of standards for clinical trainees both nationally and internationally through contributions to the National Diabetes and Endocrinology Specialist Certification Examination and the American Endocrine Society Self-Assessment Committee (SAC). I also lead the national training scheme for radioiodine administration in patients with goitre and thyrotoxicosis, directly impacting on the management of patients with thyroid neoplasia.

Looking back on my career so far, I feel incredibly lucky to have met a number of people who have helped to shape my academic path. I am forever indebted to Jayne Franklyn and Chris McCabe for providing me with their unconditional support and guidance. I have been very fortunate to be in a position to forge collaborations with high-flying researchers locally, nationally and internationally as well as to encounter a large number of very talented clinical and scientifically trained students and fellows who form part of my research group. I feel that often I have been in the right place at the right time but also that my overriding spirit of trying to grasp opportunities when they present themselves has allowed me to develop a varied and fulfilling professional life. Finally, and most importantly, I could not have under­taken this journey without the unconditional support of my husband Bhaskar and my children Nathan and Indu who continue to put up with me during the bad times as well as the good.

I started off at the bedside aiming to provide patients with the best possible care, then learned the power of science in advancing medicine to newer heights at the bench and hope to continue the translation of carefully conducted cutting-edge research back to the bedside.

Declaration of interest

The author declares that there is no conflict of interest that could be perceived as prejudicing the impartiality of this profile.

Funding

My work has been supported by Research Funding from the Wellcome Trust (066569/Z/01/Z), MRC (MR/J001414/1, G070064, G060181), NIHR-HTA (110399), NIHR-EME (09/100/10), The British Thyroid Foundation and The Get-a-Head Charity.

This paper is part of a special section on Celebrating Women in Cancer Research. The Guest Editors for this section were Charis Eng and Deborah Marsh.

References

  • Boelaert K 2009 The association between serum TSH concentration and thyroid cancer. Endocrine-Related Cancer 16 10651072. (doi:10.1677/ERC-09-0150)

    • Search Google Scholar
    • Export Citation
  • Boelaert K 2013 Thyroid dysfunction in the elderly. Nature Reviews Endocrinology 9 194204. (doi:10.1038/nrendo.2013.30)

  • Boelaert K & Franklyn JA 2003 Sodium iodide symporter: a novel strategy to target breast, prostate, and other cancers? Lancet 361 796797. (doi:10.1016/S0140-6736(03)12720-1)

    • Search Google Scholar
    • Export Citation
  • Boelaert K & Franklyn JA 2005 Thyroid hormone in health and disease. Journal of Endocrinology 187 115. (doi:10.1677/joe.1.06131)

  • Boelaert K, Horacek J, Holder RL, Watkinson JC, Sheppard MC & Franklyn JA 2006 Serum thyrotropin concentration as a novel predictor of malignancy in thyroid nodules investigated by fine-needle aspiration. Journal of Clinical Endocrinology and Metabolism 91 42954301. (doi:10.1210/jc.2006-0527)

    • Search Google Scholar
    • Export Citation
  • Boelaert K, Maisonneuve P, Torlinska B & Franklyn JA 2013 Comparison of mortality in hyperthyroidism during periods of treatment with thionamides and after radioiodine. Journal of Clinical Endocrinology and Metabolism 98 18691882. (doi:10.1210/jc.2012-3459)

    • Search Google Scholar
    • Export Citation
  • Boelaert K, McCabe CJ, Tannahill LA, Gittoes NJ, Holder RL, Watkinson JC, Bradwell AR, Sheppard MC & Franklyn JA 2003a Pituitary tumor transforming gene and fibroblast growth factor-2 expression: potential prognostic indicators in differentiated thyroid cancer. Journal of Clinical Endocrinology and Metabolism 88 23412347. (doi:10.1210/jc.2002-021113)

    • Search Google Scholar
    • Export Citation
  • Boelaert K, Tannahill LA, Bulmer JN, Kachilele S, Chan SY, Kim D, Gittoes NJ, Franklyn JA, Kilby MD & McCabe CJ 2003b A potential role for PTTG/securin in the developing human fetal brain. FASEB Journal 17 16311639. (doi:10.1096/fj.02-0948com)

    • Search Google Scholar
    • Export Citation
  • Boelaert K, Newby PR, Simmonds MJ, Holder RL, Carr-Smith JD, Heward JM, Manji N, Allahabadia A, Armitage M & Chatterjee KV et al. 2010a Prevalence and relative risk of other autoimmune diseases in subjects with autoimmune thyroid disease. American Journal of Medicine 123 183189. (doi:10.1016/j.amjmed.2009.06.030)

    • Search Google Scholar
    • Export Citation
  • Boelaert K, Torlinska B, Holder RL & Franklyn JA 2010b Older subjects with hyperthyroidism present with a paucity of symptoms and signs: a large cross-sectional study. Journal of Clinical Endocrinology and Metabolism 95 27152726. (doi:10.1210/jc.2009-2495)

    • Search Google Scholar
    • Export Citation
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  • Smith VE, Read ML, Turnell AS, Watkins RJ, Watkinson JC, Lewy GD, Fong JC, James SR, Eggo MC & Boelaert K et al. 2009 A novel mechanism of sodium iodide symporter repression in differentiated thyroid cancer. Journal of Cell Science 122 33933402. (doi:10.1242/jcs.045427)

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  • Smith VE, Sharma N, Watkins RJ, Read ML, Ryan GA, Kwan PP, Martin A, Watkinson JC, Boelaert K & Franklyn JA et al. 2013 Manipulation of PBF/PTTG1IP phosphorylation status; a potential new therapeutic strategy for improving radioiodine uptake in thyroid and other tumors. Journal of Clinical Endocrinology and Metabolism 98 28762886. (doi:10.1210/jc.2012-3640)

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  • Stratford AL, Boelaert K, Tannahill LA, Kim DS, Warfield A, Eggo MC, Gittoes NJ, Young LS, Franklyn JA & McCabe CJ 2005 Pituitary tumor transforming gene binding factor: a novel transforming gene in thyroid tumorigenesis. Journal of Clinical Endocrinology and Metabolism 90 43414349. (doi:10.1210/jc.2005-0523)

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  • Tannahill LA, Visser TJ, McCabe CJ, Kachilele S, Boelaert K, Sheppard MC, Franklyn JA & Gittoes NJ 2002 Dysregulation of iodothyronine deiodinase enzyme expression and function in human pituitary tumours. Clinical Endocrinology 56 735743. (doi:10.1046/j.1365-2265.2002.01541.x)

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  • Vanderpump MP, Lazarus JH, Smyth PP, Laurberg P, Holder RL, Boelaert K & Franklyn JA 2011 Iodine status of UK schoolgirls: a cross-sectional survey. Lancet 377 20072012. (doi:10.1016/S0140-6736(11)60693-4)

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  • Zimmermann MB & Boelaert K 2015 Iodine deficiency and thyroid disorders. Lancet Diabetes and Endocrinology 3 286295. (doi:10.1016/S2213-8587(14)70225-6)

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  • Boelaert K 2009 The association between serum TSH concentration and thyroid cancer. Endocrine-Related Cancer 16 10651072. (doi:10.1677/ERC-09-0150)

    • Search Google Scholar
    • Export Citation
  • Boelaert K 2013 Thyroid dysfunction in the elderly. Nature Reviews Endocrinology 9 194204. (doi:10.1038/nrendo.2013.30)

  • Boelaert K & Franklyn JA 2003 Sodium iodide symporter: a novel strategy to target breast, prostate, and other cancers? Lancet 361 796797. (doi:10.1016/S0140-6736(03)12720-1)

    • Search Google Scholar
    • Export Citation
  • Boelaert K & Franklyn JA 2005 Thyroid hormone in health and disease. Journal of Endocrinology 187 115. (doi:10.1677/joe.1.06131)

  • Boelaert K, Horacek J, Holder RL, Watkinson JC, Sheppard MC & Franklyn JA 2006 Serum thyrotropin concentration as a novel predictor of malignancy in thyroid nodules investigated by fine-needle aspiration. Journal of Clinical Endocrinology and Metabolism 91 42954301. (doi:10.1210/jc.2006-0527)

    • Search Google Scholar
    • Export Citation
  • Boelaert K, Maisonneuve P, Torlinska B & Franklyn JA 2013 Comparison of mortality in hyperthyroidism during periods of treatment with thionamides and after radioiodine. Journal of Clinical Endocrinology and Metabolism 98 18691882. (doi:10.1210/jc.2012-3459)

    • Search Google Scholar
    • Export Citation
  • Boelaert K, McCabe CJ, Tannahill LA, Gittoes NJ, Holder RL, Watkinson JC, Bradwell AR, Sheppard MC & Franklyn JA 2003a Pituitary tumor transforming gene and fibroblast growth factor-2 expression: potential prognostic indicators in differentiated thyroid cancer. Journal of Clinical Endocrinology and Metabolism 88 23412347. (doi:10.1210/jc.2002-021113)

    • Search Google Scholar
    • Export Citation
  • Boelaert K, Tannahill LA, Bulmer JN, Kachilele S, Chan SY, Kim D, Gittoes NJ, Franklyn JA, Kilby MD & McCabe CJ 2003b A potential role for PTTG/securin in the developing human fetal brain. FASEB Journal 17 16311639. (doi:10.1096/fj.02-0948com)

    • Search Google Scholar
    • Export Citation
  • Boelaert K, Newby PR, Simmonds MJ, Holder RL, Carr-Smith JD, Heward JM, Manji N, Allahabadia A, Armitage M & Chatterjee KV et al. 2010a Prevalence and relative risk of other autoimmune diseases in subjects with autoimmune thyroid disease. American Journal of Medicine 123 183189. (doi:10.1016/j.amjmed.2009.06.030)

    • Search Google Scholar
    • Export Citation
  • Boelaert K, Torlinska B, Holder RL & Franklyn JA 2010b Older subjects with hyperthyroidism present with a paucity of symptoms and signs: a large cross-sectional study. Journal of Clinical Endocrinology and Metabolism 95 27152726. (doi:10.1210/jc.2009-2495)

    • Search Google Scholar
    • Export Citation
  • Boelaert K, Smith VE, Stratford AL, Kogai T, Tannahill LA, Watkinson JC, Eggo MC, Franklyn JA & McCabe CJ 2007 PTTG and PBF repress the human sodium iodide symporter. Oncogene 26 43444356. (doi:10.1038/sj.onc.1210221)

    • Search Google Scholar
    • Export Citation
  • Boelaert K, Syed AA, Manji N, Sheppard MC, Holder RL, Gough SC & Franklyn JA 2009 Prediction of cure and risk of hypothyroidism in patients receiving 131I for hyperthyroidism. Clinical Endocrinology 70 129138. (doi:10.1111/j.1365-2265.2008.03291.x)

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  • Boelaert K, Yu R, Tannahill LA, Stratford AL, Khanim FL, Eggo MC, Moore JS, Young LS, Gittoes NJ & Franklyn JA et al. 2004 PTTG’s C-terminal PXXP motifs modulate critical cellular processes in vitro. Journal of Molecular Endocrinology 33 663677. (doi:10.1677/jme.1.01606)

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  • Brabant G, Peeters RP, Chan SY, Bernal J, Bouchard P, Salvatore D, Boelaert K & Laurberg P 2015 Management of subclinical hypothyroidism in pregnancy: are we too simplistic? European Journal of Endocrinology 173 111. (doi:10.1530/EJE-14-1005)

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  • Chan S & Boelaert K 2014 Optimal management of hypothyroidism, hypothyroxinaemia and euthyroid TPO antibody positivity pre-conception and in pregnancy. Clinical Endocrinology 82 313326. (doi:10.1111/cen.12605)

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  • Chortis V, Edmunds MR, Littleton ET & Boelaert K 2014 Autoimmune encephalopathy in the context of Graves’ disease with ophthalmopathy. Clinical Endocrinology 81 936937. (doi:10.1111/cen.12448)

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  • Daniel E, Aylwin S, Mustafa O, Ball S, Munir A, Boelaert K, Chortis V, Cuthbertson DJ, Daousi C & Rajeev SP et al. 2015 Effectiveness of metyrapone in treating Cushing’s syndrome: a retrospective multicenter study in 195 patients. Journal of Clinical Endocrinology and Metabolism 100 41464154. (doi:10.1210/jc.2015-2616)

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  • Edmunds MR, Denniston AK, Boelaert K, Franklyn JA & Durrani OM 2014 Patient information in Graves’ disease and thyroid-associated ophthalmopathy: readability assessment of online resources. Thyroid 24 6772. (doi:10.1089/thy.2013.0252)

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  • Edmunds MR, Mellington F, Ford RL, Torlinska B, Manavi K & Boelaert K 2015 Clinical challenges of thyroid eye disease in HIV-positive patients on highly active antiretroviral therapy. Journal of Clinical Endocrinology and Metabolism 100 779787. (doi:10.1210/jc.2014-3544)

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  • Essig GF Jr, Porter K, Schneider D, Debora A, Lindsey SC, Busonero G, Fineberg D, Fruci B, Boelaert K & Smit JW et al. 2013 Fine needle aspiration and medullary thyroid carcinoma: the risk of inadequate preoperative evaluation and initial surgery when relying upon FNAB cytology alone. Endocrine Practice 19 920927. (doi:10.4158/EP13143.OR)

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  • Franklyn JA & Boelaert K 2012 Thyrotoxicosis. Lancet 379 11551166. (doi:10.1016/S0140-6736(11)60782-4)

  • Jones CM & Boelaert K 2015 The endocrinology of ageing: a mini-review. Gerontology 61 291300. (doi:10.1159/000367692)

  • Kim CS, Ying H, Willingham MC & Cheng SY 2006a The pituitary tumor transforming gene promotes angiogenesis in a mouse model of follicular thyroid cancer. Carcinogenesis 28 932939. (doi:10.1093/carcin/bgl231)

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  • Kim DS, Franklyn JA, Boelaert K, Eggo MC, Watkinson JC & McCabe CJ 2006b Pituitary tumor transforming gene (PTTG) stimulates thyroid cell proliferation via a vascular endothelial growth factor/kinase insert domain receptor/inhibitor of DNA binding-3 autocrine pathway. Journal of Clinical Endocrinology and Metabolism 91 46034611. (doi:10.1210/jc.2006-1291)

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  • Kim D, Pemberton H, Stratford AL, Buelaert K, Watkinson JC, Lopes V, Franklyn JA & McCabe CJ 2005 Pituitary tumour transforming gene (PTTG) induces genetic instability in thyroid cells. Oncogene 24 48614866. (doi:10.1038/sj.onc.1208659)

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  • Lewy GD, Ryan GA, Read ML, Fong JC, Poole V, Seed RI, Sharma N, Smith VE, Kwan PP & Stewart SL et al. 2013 Regulation of pituitary tumor transforming gene (PTTG) expression and phosphorylation in thyroid cells. Endocrinology 154 44084422. (doi:10.1210/en.2012-2156)

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  • Manji N, Boelaert K, Sheppard MC, Holder RL, Gough SC & Franklyn JA 2006a Lack of association between serum TSH or free T4 and body mass index in euthyroid subjects. Clinical Endocrinology 64 125128. (doi:10.1111/j.1365-2265.2006.02433.x)

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  • Manji N, Carr-Smith JD, Boelaert K, Allahabadia A, Armitage M, Chatterjee VK, Lazarus JH, Pearce SH, Vaidya B & Gough SC et al. 2006b Influences of age, gender, smoking, and family history on autoimmune thyroid disease phenotype. Journal of Clinical Endocrinology and Metabolism 91 48734880. (doi:10.1210/jc.2006-1402)

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  • McCabe CJ, Boelaert K, Tannahill LA, Heaney AP, Stratford AL, Khaira JS, Hussain S, Sheppard MC, Franklyn JA & Gittoes NJ 2002 Vascular endothelial growth factor, its receptor KDR/Flk-1, and pituitary tumor transforming gene in pituitary tumors. Journal of Clinical Endocrinology and Metabolism 87 42384244. (doi:10.1210/jc.2002-020309)

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  • McCabe CJ, Khaira JS, Boelaert K, Heaney AP, Tannahill LA, Hussain S, Mitchell R, Olliff J, Sheppard MC & Franklyn JA et al. 2003 Expression of pituitary tumour transforming gene (PTTG) and fibroblast growth factor-2 (FGF-2) in human pituitary adenomas: relationships to clinical tumour behaviour. Clinical Endocrinology 58 141150. (doi:10.1046/j.1365-2265.2003.01598.x)

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  • Mehanna H, Al-Maqbili T, Carter B, Martin E, Campain N, Watkinson J, McCabe C, Boelaert K & Franklyn JA 2014 Differences in the recurrence and mortality outcomes rates of incidental and nonincidental papillary thyroid microcarcinoma: a systematic review and meta-analysis of 21,329 person-years of follow-up. Journal of Clinical Endocrinology and Metabolism 99 28342843. (doi:10.1210/jc.2013-2118)

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  • Monahan M, Boelaert K, Jolly K, Chan S, Barton P & Roberts TE 2015 Costs and benefits of iodine supplementation for pregnant women in a mildly to moderately iodine-deficient population: a modelling analysis. Lancet Diabetes and Endocrinology 3 715722. (doi:10.1016/S2213-8587(15)00212-0)

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  • Pemberton HN, Franklyn JA, Boelaert K, Chan SY, Kim DS, Kim C, Cheng SY, Kilby MD & McCabe CJ 2007 Separase, securin and Rad21 in neural cell growth. Journal of Cellular Physiology 213 4553. (doi:10.1002/jcp.21086)

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  • Perros P, Boelaert K, Colley S, Evans C, Evans RM, Gerrard BG, Gilbert J, Harrison B, Johnson SJ & Giles TE et al. 2014 Guidelines for the management of thyroid cancer. Clinical Endocrinology 81 (Supplement 1) 1122. (doi:10.1111/cen.12515)

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  • Rabbitt EH, Ayuk J, Boelaert K, Sheppard MC, Hewison M, Stewart PM & Gittoes NJ 2003 Abnormal expression of 11 beta-hydroxysteroid dehydrogenase type 2 in human pituitary adenomas: a prereceptor determinant of pituitary cell proliferation. Oncogene 22 16631667. (doi:10.1038/sj.onc.1206293)

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  • Read ML, Lewy GD, Fong JC, Sharma N, Seed RI, Smith VE, Gentilin E, Warfield A, Eggo MC & Knauf JA et al. 2011 Proto-oncogene PBF/PTTG1IP regulates thyroid cell growth and represses radioiodide treatment. Cancer Research 71 61536164. (doi:10.1158/0008-5472.CAN-11-0720)

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  • Read ML, Seed RI, Modasia B, Kwan PP, Sharma N, Smith VE, Watkins RJ, Bansal S, Gagliano T & Stratford AL et al. 2016 The proto-oncogene PBF binds p53 and is associated with prognostic features in colorectal cancer. Molecular Carcinogenesis 55 1526. (doi:10.1002/mc.22254)

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  • Smith VE, Read ML, Turnell AS, Sharma N, Lewy GD, Fong JC, Seed RI, Kwan P, Ryan G & Mehanna H et al. 2012 PTTG-binding factor (PBF) is a novel regulator of the thyroid hormone transporter MCT8. Endocrinology 153 35263536. (doi:10.1210/en.2011-2030)

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  • Smith VE, Read ML, Turnell AS, Watkins RJ, Watkinson JC, Lewy GD, Fong JC, James SR, Eggo MC & Boelaert K et al. 2009 A novel mechanism of sodium iodide symporter repression in differentiated thyroid cancer. Journal of Cell Science 122 33933402. (doi:10.1242/jcs.045427)

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  • Smith VE, Sharma N, Watkins RJ, Read ML, Ryan GA, Kwan PP, Martin A, Watkinson JC, Boelaert K & Franklyn JA et al. 2013 Manipulation of PBF/PTTG1IP phosphorylation status; a potential new therapeutic strategy for improving radioiodine uptake in thyroid and other tumors. Journal of Clinical Endocrinology and Metabolism 98 28762886. (doi:10.1210/jc.2012-3640)

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  • Stratford AL, Boelaert K, Tannahill LA, Kim DS, Warfield A, Eggo MC, Gittoes NJ, Young LS, Franklyn JA & McCabe CJ 2005 Pituitary tumor transforming gene binding factor: a novel transforming gene in thyroid tumorigenesis. Journal of Clinical Endocrinology and Metabolism 90 43414349. (doi:10.1210/jc.2005-0523)

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  • Tannahill LA, Visser TJ, McCabe CJ, Kachilele S, Boelaert K, Sheppard MC, Franklyn JA & Gittoes NJ 2002 Dysregulation of iodothyronine deiodinase enzyme expression and function in human pituitary tumours. Clinical Endocrinology 56 735743. (doi:10.1046/j.1365-2265.2002.01541.x)

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  • Vanderpump MP, Lazarus JH, Smyth PP, Laurberg P, Holder RL, Boelaert K & Franklyn JA 2011 Iodine status of UK schoolgirls: a cross-sectional survey. Lancet 377 20072012. (doi:10.1016/S0140-6736(11)60693-4)

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  • Watkins RJ, Read ML, Smith VE, Sharma N, Reynolds GM, Buckley L, Doig C, Campbell MJ, Lewy G & Eggo MC et al. 2010 Pituitary tumor transforming gene binding factor: a new gene in breast cancer. Cancer Research 70 37393749. (doi:10.1158/0008-5472.CAN-09-3531)

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  • Zimmermann MB & Boelaert K 2015 Iodine deficiency and thyroid disorders. Lancet Diabetes and Endocrinology 3 286295. (doi:10.1016/S2213-8587(14)70225-6)

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