Graduate Research Prize Winners 2012
I completed my medical training in Oxford and during my undergraduate course had the opportunity to undertake an 8 week laboratory project in Professor Paul Wordsworth’s group at the Wellcome Trust Centre for Human Genetics, when it was located at the Nuffield Orthopaedic Centre. Under the supervision of Dr Matthew Brown and Prof Wordsworth I completed a project assessing a gene encoding ‘secretor status’ as a candidate for involvement in the pathogenesis of ankylosing spondylitis. This really stirred my interest in genetics and also gave me a taster for the rewards (and challenges) of research.
Just over 10 years later, having been drawn to the speciality of Diabetes and Endocrinology and inspired by the enthusiasm of several academic clinicians along the way (Professor John Wass, Professor David Matthews, Dr Amanda Adler), I was fortunate enough to get the chance to work with Dr Katherine Owen, Dr Anna Gloyn and Professor Mark McCarthy as an NIHR Clinical Research Fellow. We investigated ways to delineate the various genetic subtypes of diabetes using simple clinical indicators and biomarkers as screening tools to target the most likely individuals in whom to perform genetic testing for the rarer monogenic forms of diabetes. In particular I worked on a project using serum 1,5 anhydroglucitol to differentiate cases of HNF1A MODY from other MODY (maturity onset diabetes of the young) subtypes and type 1 and type 2 diabetes. I also worked on a project aiming to identify cases of ‘atypical type 1 diabetes’ in order to target genetic testing for MODY.
Within this group I was able to gain an MRC Clinical Training Research Fellowship, under the supervision of Anna Gloyn and Mark McCarthy, to embark on a project that forms the basis for my PhD studies. Thanks to them, I got the opportunity to work on a project investigating the aetiological mechanisms at play in the epidemiological overlap between type 2 diabetes and cancer. I have been investigating the role of three well recognised tumour suppressor genes (CDKN2A, CDKN2B and PTEN) in glucose homeostasis and T2D pathogenesis. This project has given me the chance to use clinical experience gained as a medic to date whilst also providing ample opportunity to learn complex laboratory techniques in a very well supported research group. Our PTEN studies have led us to describe one of the first recognised syndromes of constitutive insulin sensitivity: using hyperinsulinaemic euglycaemic clamps and other physiological tests we have shown that individuals with PTEN mutations demonstrate profound insulin sensitivity compared to age, gender, BMI and activity matched control subjects.
As well as a taste for fine coffee, my time as a graduate student has given me an excellent foundation in academic medicine on a project that has married both intense laboratory research as well as physiological studies. I will look back on this period as one of my most enjoyable, productive and high points in training.
Pal A, Barber TM, Van de Bunt M, Rudge SA, Zhang Q, Lachlan KL, Cooper NS, Linden H, Levy JC, Wakelam MJ, Walker L, Karpe F, Gloyn AL. PTEN mutations as a cause of constitutive insulin sensitivity and obesity in humans. N Engl J Med. 2012 Sep 13;367(11):1002-11.
G Thanabalasingham, A Pal, M Selwood, C Dudley, K Fisher, P Bingley, S Ellard, A Farmer, M McCarthy, K Owen. Systematic assessment of Etiology in Adults with a Clinical Diagnosis of Young-Onset Type 2 Diabetes is a successful strategy for identifying Maturity-Onset Diabetes of the Young. Diabetes Care. 2012 Jun;35(6):1206-12
A Pal, C Capatina, AP Tenreiro, PD Guardiola, JV Byrne, S Cudlip, N Karavitaki and JAH Wass. Pituitary apoplexy in non functioning pituitary adenomas – long term follow up is important because of significant numbers of tumour recurrences. Clinical Endocrinol. 2011 Oct;75(4):501-4
Pal A, Farmer AJ, Dudley C, Selwood MP, Klyne R, Grew JP, McCarthy MI, Gloyn AL, Owen KR. Evaluation of serum 1,5 anhydroglucitol levels as a clinical test to differentiate subtypes of diabetes. Diabetes Care 2010 Feb;33(2):252-7