Molecular pathogenesis of endocrine cancers
Diagnosis, management and long-term consequences of thyroid dysfunction
Investigation of novel diagnostic and therapeutic approaches in thyroid nodules and cancer
1. Laboratory Research
Kristien’s laboratory research interests centre around the molecular pathogenesis of endocrine cancers in general and thyroid tumours specifically. In particular the role played by two closely related proto-oncogenes namely PTTG – the human securin - which has been implicated in the aetiology of a number of endocrine tumour types and its binding factor PBF, a proto-oncogene which we is currently being characterised in collaboration with Professor Chris McCabe.
Utilising several models of altered gene expression and function in the murine thyroid, we are currently mapping the multiple actions of PTTG and PBF in the initiation and progression of transformed cell growth. We are characterising the altered growth factor regulation apparent in thyroid hyperplasia and neoplasia, through mouse models, human primary thyroid cultures and transformed thyroid cell line investigations.
Both PTTG and PBF have been shown to reduce the function of the sodium iodide symporter which is the molecule responsible for iodide uptake in thyroid cells, a finding which has major implications for the treatment of thyroid cancers with radioactive iodine. We are in the process of developing systems through which uptake of radioiodine may be modulated in vivo, thereby exploring novel therapeutic approaches for patients with thyroid cancer.
2. Translational Research
Kristien continues to be involved in a number of research projects aiming to improve the management of patients with hyperthyroidism. These include projects determining the prevalence of symptoms and signs in patients with subclinical and overt hyperthyroidism, the risk of co-existing autoimmune diseases in patients with autoimmune thyroid disease, and outcomes following administration of radioactive iodine. Currently ongoing studies include the prediction of mortality in patients with hyperthyroidism according to the treatment modality used and the effects of treatment of hyperthyroidism on BMI. Current funding applications centre around the hypothesis that weight gain following treatment of hyperthyroidism may be prevented through simple interventions including dietary and lifestyle changes.
Based on findings within the laboratory Kristien is in the process of setting up a number of research projects indentifying novel diagnostic and prognostic markers in patients with thyroid nodules. This includes investigations of the predictive value of serum TSH concentrations in predicting malignancy as well as the evaluation of molecular tools to aid in the distinction between benign and malignant thyroid nodules. An upcoming Visiting Clinician Fellowship at the Mayo Clinic, Rochester Minnesota will be pivotal in further expanding these research avenues.
Original Research publications (8 most recent)
K Boelaert, B Torlinska, RL Holder and JA Franklyn (2010). Older subjects with hyperthyroidism present with a paucity of symptoms and signs – a large cross-sectional study. Journal of Clinical Endocrinology and Metabolism, 95: 2715-2726.
RJ Watkins, ML Read, VE Smith, GM Reynolds, L Buckley, G Lewy, MC Eggo, LS Loubiere, K JA Franklyn, K Boelaert and CJ McCabe (2010). PTTG Binding Factor – a New Gene in Breast Cancer Cancer Research, 70: 3739-3749.
K Boelaert, PR Newby, MJ Simmonds, RL Holder, JD Carr-Smith, JM Heward, A Allahabadia, M Armitage, VK Chatterjee, JH Lazarus, SHS Pearce, B Vaidya, SC Gough, and JA Franklyn (2010). Prevalence and relative risk of other autoimmune diseases in subjects with autoimmune thyroid disease. American Journal of Medicine, 123: 183.e1-9.
VE Smith, ML Read, A Turnell, RJ Watkins, SR James, MC Eggo, K Boelaert, JA Franklyn and CJ McCabe (2009). A novel mechanism of sodium iodide symporter repression in differentiated thyroid cancer. Journal of Cell Science, 122: 3393-4302.
K Boelaert, A Syed, N Manji, RL Holder, MC Sheppard, SC Gough and JA Franklyn (2009). Prediction of cure and risk of hypothyroidism in patients receiving 131I for hyperthyroidism. Clinical Endocrinology, 70: 129-138.
K Boelaert, VE Smith, AL Stratford, T Kogai, LA Tannahill, JC Watkinson, MC Eggo, JA Franklyn and CJ McCabe (2007). PTTG and PBF repress the human sodium iodide symporter. Oncogene, 26: 4344-4356.
HN Pemberton, JA Franklyn, K Boelaert, SY Chan, DS Kim, C Kim, SY Cheng, S Melmed, MD Kilby and CJ McCabe (2007). Separase, securin and Rad21 in neural cell growth. Journal of Cellular Physiology 2007 Journal of Cellular Physiology, 213: 45-53.
K Boelaert, J Horacek, RL Holder, JC Watkinson, MC Sheppard and JA Franklyn (2006). Serum thyrotropin concentration as a novel predictor of malignancy in thyroid nodules investigated by fine needle aspiration biopsy. Journal of Clinical Endocrinology and Metabolism, 91: 4295-4301.
K Boelaert (2010). Thyroid gland: Revised guidelines for the management of thyroid cancer. Nature Reviews in Endocrinology, 6: 185-186.
K Boelaert (2010). Treatment of Graves’ disease with antithyroid drugs: Current perspectives. Thyroid, 20: 943-946.
N Sharma, K Boelaert and JC Watkinson (2010). Who should treat thyroid cancer? A UK surgical perspective. Clinical Oncology, 22:413-418
K Boelaert (2009). The association between TSH and Thyroid cancer. Endocrine Related Cancer, 16: 1065-1072.
K Boelaert and JA Franklyn. Starling Review: Thyroid hormone in health and disease. Journal of Endocrinology, 187: 1-15.
K Boelaert and NJ Gittoes. Radiotherapy for non-functioning pituitary adenomas. European Journal of Endocrinology, 144: 569-75.
K Boelaert (2010). Thyroid hormones, iodine and antithyroid drugs In Side Effects of Drugs Annual Volume 32 (in press)
K Boelaert, L Albon, and JA Franklyn (2010). Benign Thyroid Disease, In Stell and Maran's Textbook of Head and Neck Surgery and Oncology, 5th Edition (in press)
K Boelaert, JV Parle and JA Franklyn (2010). Thyroid Disease, In Endocrinology in Primary Care, pp125-165, Ed N Gittoes, National services for Health Improvement, Nuffield Press Ltd, Dartford, UK.