Dr Robert Semple

Director of Studies in Clinical Medicine

Wellcome Trust Clinician Scientist Fellow

t: (01223) 769035

e: rks16@cam.ac.uk

Main Publications:

Postreceptor insulin resistance contributes to human dyslipidemia and hepatic steatosis, Semple, RK; Sleigh, A; Murgatroyd, PR; Adams, CA; Bluck, L; Jackson, S; Vottero, A; Kanabar, D; Charlton-Menys, V; Durrington, P; Soos, MA; Carpenter, TA; Lomas, DJ; Cochran, EK; Gorden, P; O'Rahilly, S; Savage, DB, J Clin Invest,119 (2), 315-22 (2009)

TAC3 and TACR3 mutations in familial hypogonadotropic hypogonadism reveal a key role for Neurokinin B in the central control of reproduction, Topaloglu, AK; Reimann, F; Guclu, M; Yalin, AS; Kotan, LD; Porter, KM; Serin, A; Mungan, NO; Cook, JR; Ozbek, MN; Imamoglu, S; Akalin, NS; Yuksel, B; O'Rahilly, S; Semple, RK, Nat Genet, 41 (3), 354-8 (2009)

Plasma adiponectin as a marker of insulin receptor dysfunction: clinical utility in severe insulin resistance, Semple, RK; Cochran, EK; Soos, MA; Burling, KA; Savage, DB; Gorden, P; O'Rahilly, S, Diabetes Care, 31 (5), 977-9 (2008)

Mutations in the pericentrin (PCNT) gene cause primordial dwarfism, Rauch, A; Thiel, CT; Schindler, D; Wick, U; Crow, YJ; Ekici, AB; van Essen, AJ; Goecke, TO; Al-Gazali, L; Chrzanowska, KH; Zweier, C; Brunner, HG; Becker, K; Curry, CJ; Dallapiccola, B; Devriendt, K; Dörfler, A; Kinning, E; Megarbane, A; Meinecke, P; Semple, RK; Spranger, S; Toutain, A; Trembath, RC; Voss, E; Wilson, L; Hennekam, R; de Zegher, F; Dörr, HG; Reis, A, Science, 8, 816-9 (2008)

Paradoxical elevation of high-

molecular weight adiponectin in acquired extreme insulin resistance due to insulin receptor antibodies, Semple, RK; Halberg, NH; Burling, K; Soos, MA; Schraw, T; Luan, J; Cochran, EK; Dunger, DB; Wareham, NJ; Scherer, PE; Gorden, P; O'Rahilly, S, Diabetes, 56 (6), 1712-7 (2007)

Elevated plasma adiponectin in humans with genetically defective insulin receptors, Semple, RK; Soos, MA; Luan, J; Mitchell, CS; Wilson, JC; Gurnell, M; Cochran, EK; Gorden, P; Chatterjee, VK; Wareham, NJ; O'Rahilly, S, J Clin Endocrinol Metab, 91 (8), 3219-23 (2006)

Two novel missense mutations in g protein-coupled receptor 54 in a patient with hypogonadotropic hypogonadism, Semple, RK; Achermann, JC; Ellery, J; Farooqi, IS; Karet, FE; Stanhope, RG; O'Rahilly, S; Aparicio, SA, J Clin Endocrinol Metab, 90 (3), 1849-55 (2005)

What is your subject and specific area of study?

I am a clinical doctor specialising in Diabetes and Endocrinology as well as a scientist, and so my research work focuses heavily on understanding genetic, cellular and physiological aspects of human disease, in particular type 2 diabetes, which is now among the greatest healthcare challenges in the world today. Specifically, I focus on the genetic, cellular and molecular basis of human severe insulin resistance and extreme insulin hypersensitivity, and on the mechanisms linking abnormalities of insulin action to disorders of growth and reproductive function. There is a major translational element to my work, centred on improving diagnosis and treatment of patients with severe insulin resistance. Key analytic approaches adopted include clinical phenotyping of humans with rare inherited syndromes, the dissection of insulin action in primary cells from affected patients, and the identification of causative genetic defects using various genetic approaches. I am also interested in the regulation of the hypothalamic-pituitary-gonadal axis, with specific reference to genetic disorders leading to failure of puberty.

What makes Clare College such a good place to study your subject?

Studying Medicine in Cambridge offers tremendous opportunities, but also significant challenges compared to many other medical course.  The most prominent feature of the course is the exposure to the full range of cutting edge biomedical science in Cambridge, with the opportunity to spend the third year studying for a BA with pure science students, or indeed studying for a BA in a wide range of other non scientific fields within the university.  Coupled to this academic opportunity, however, there is a need to start developing the professional attitudes which will form the basis for later clinical training.  Sometimes this can seem daunting, and Clare is lucky to have a strong medical community both among the fellowship, which includes clinical doctors, clinician scientists, and pure scientists, and also among the MCR, where many trained doctors are undertaking studies towards a PhD.  This wide community provides not only an excellent range of mentoring for undergraduate students, but also promotes scientific and medical interactions at all levels.  In addition, Clare is lucky to have strong links with other institutions, most notably with Prof Mark Poznansky, a former fellow, at Massachussetts General Hospoital, and every year Clare undergraduate and clinical medical students have the chance to compete for prestigious summer placements at MGH.