The group is committed to understanding the diverse range of specific mechanisms underlying endocrine cancer, with particular focus on thyroid tumourigenesis. Amongst this, two proto-oncogenes are of intense interest to us: (1) PTTG – the human securin – which is implicated in the aetiology of a number of endocrine tumour types, and (2) PBF – the binding partner of PTTG, which we are world leaders in characterising.
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 developing systems through which we are able to modulate radioiodine uptake in vivo, to mimic the central treatment of human thyroid cancer. Further, we are characterising the altered growth factor regulation apparent in thyroid hyperplasia and neoplasia, through murine models, human primary thyroid culture and thyroid cell investigations.
On the back of the recently completed HiLo Phase III Clinical Trial in which over 400 patients with thyroid cancer were given varying radioiodine doses with and without rTSH treatments, we are determining the contribution of altered PTTG and PBF signalling to clinical outcome. A central theme of this and other studies is the role of PTTG and PBF in driving genetic instability and interfering with DNA repair in thyroid cancer. Further, to investigate precisely how PBF mediates its actions in thyroid and other cancers, we are evaluating a number of novel interacting partners identified through extensive mass spec screening. Outside thyroid cancer research, we are assessing the role of PBF in breast and colon cancer, the latter involving a newly constructed model of PBF over-expression in the murine GI tract.
A wider appraisal of the myriad mechanisms by which hormones influence tumourigenesis comes from our recently funded Endocrine Cancer consortium, which spans the School of Clinical and Experimental Medicine and the School of Cancer Sciences. This group of leading PIs has recently recruited 2 excellent PhD students, who will pursue student-led projects spanned between the centres of excellence at the University of Birmingham.
Chris McCabe (group lead)
Professor Of Molecular Endocrinology
Dr Kristien Boelaert
MRC Clinician Scientist and Honorary Consultant Endocrinologist
Professor Jayne Franklyn
Head of School of Clinical and Experimental Medicine and William Withering Professor of Medicine
Dr Andrew Turnell
Dr Ashley Martin
The Endocrine Cancer Consortium
Dr Chris Tselpis
Prof Wiebke Arlt
Dr Jeremy Tomlinson
Prof Ulrich Guenther
Prof Eamonn Maher
Dr Grant Stewart