Diseases of human metabolic health where energy balance is disordered are significant medical and socioeconomic problems. Meaningful intervention requires an understanding of the processes involved. My research aims to investigate how disorders of energy balance can result from disruption of the pathways that control how we eat, how we metabolise fuel and how we store excess energy in tissue. The basis of these studies comes primarily from studies of human disease, including rare genetic forms of obesity and larger population-based genetic studies.
Our current understanding of the central control of appetite has relied heavily upon mouse models and I continue to combine murine genetics and whole animal physiological studies to address these issues. I have a longstanding interest in the leptin-melanocortin pathway and in collaboration with colleagues in the IMS (O’Rahilly, Farooqi, Yeo) continue to use murine models to gain a more mechanistic understanding of how pathways highlighted by human genetic studies can malfunction and result in metabolic disorders.
Larder R, Sim MFM, Gulati P, Antrobus R, Tung YCL, Rimmington D, Ayuso E, Polex-Wolf J, Lam BYH, Dias C, Logan DW, Virtue S, Bosch F, Yeo GSH, Saudek V, O’Rahilly S, Coll AP. Obesity-associated gene TMEM18 has a role in the central control of appetite and body weight regulation. Proc. Natl. Acad. Sci. U.S.A. 2017, in Press
Flint TR, Janowitz T, Connell CM, Roberts EW, Denton AE, Coll AP, Jodrell DI, Fearon DT. Tumor-induced IL-6 reprograms host metabolism to suppress anti-tumor immunity. Cell Metabolism, 2016 Nov 8: 24(5):672-684. PMID: 27829137.
Novoselova TV, Larder R, Rimmington D, Lelliott C, Wynn EH, Gorrigan RJ, Tate PH, Guasti L; Sanger Mouse Genetics Project, O’Rahilly S, Clark AJ, Logan DW, Coll AP, Chan LF. Loss of Mrap2 is associated with Sim1 deficiency and increased circulating cholesterol. J Endocrinol. 2016 Jul;230(1):13-26. PMID: 27106110.
Dalgaard K, Landgraf K, Heyne S, Lempradl A, Longinotto J, Gossens K, Ruf M,Orthofer M, Strogantsev R, Selvaraj M, Lu TT, Casas E, Teperino R, Surani MA, Zvetkova I, Rimmington D, Tung YC, Lam B, Larder R, Yeo GS, O’Rahilly S, Vavouri T, Whitelaw E, Penninger JM, Jenuwein T, Cheung CL, Ferguson-Smith AC, Coll AP, Körner A, Pospisilik JA. Trim28 Haploinsufficiency Triggers Bi-stable Epigenetic Obesity. Cell. 2016 Jan 28;164(3):353-64 PMID: 26824653
Tung YC, Gulati P, Liu CH, Rimmington D, Dennis R, Ma M, Saudek V, O’Rahilly S, Coll AP, Yeo GS. FTO is necessary for the induction of leptin resistance by high-fat feeding. Mol Metab. 2015 Feb 7;4(4):287-98. PMID: 25830092
Grosse J, Heffron H, Burling K, Akhter Hossain M, Habib AM, Rogers GJ, Richards P, Larder R, Rimmington D, Adriaenssens AA, Parton L, Powell J, Binda M, Colledge WH, Doran J, Toyoda Y, Wade JD, Aparicio S, Carlton MB, Coll AP, Reimann, F, O’Rahilly S, Gribble FM. Insulin-like peptide 5 is an orexigenic gastrointestinal hormone. Proc Natl Acad Sci U S A. 2014 Jul 29;111(30):11133-8. PMID: 25028498.
Gulati P, Cheung MK, Antrobus R, Church CD, Harding HP, Tung YC, Rimmington D, Ma M, Ron D, Lehner PJ, Ashcroft FM, Cox RD, Coll AP, O’Rahilly S, Yeo GS. Role for the obesity-related FTO gene in the cellular sensing of amino acids. Proc Natl Acad Sci U S A. 2013 Feb 12;110(7):2557-62. PMID: 23359686. PMCID: PMC3574930.
McMurray F, Church CD, Larder R, Nicholson G, Wells S, Teboul L, Tung YC, Rimmington D, Bosch F, Jimenez V, Yeo GS, O’Rahilly S, Ashcroft FM, Coll AP, Cox RD. Adult onset global loss of the Fto gene alters body composition and metabolism in the mouse. PLoS Genet. 2013 Jan;9(1):e1003166. PMID: 23300482