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.
In collaboration with colleagues in the IMS (O’Rahilly, Yeo) my work aims to gain a more mechanistic understanding of how pathways highlighted by these human genetic studies can malfunction and result in metabolic disorders.
Our current understanding of the central control of appetite has relied heavily upon mouse models and I combine murine genetics and whole animal physiological studies to address these issues, in particular how signals from peripheral organs are integrated within the brain to change appetitive behaviour.
Coll AP, Chen M, Taskar P, Rimmington D, Patel S, Tadross J, Cimino I, Yang M,Welsh P, Virtue S, Goldspink DA, Miedzybrodzka EL, Konopka AR, Esponda RR, Huang JT, Tung YCL, Rodriguez-Cuenca S, Tomaz RA, Harding HP, Melvin A, Yeo GSH, Preiss D, Vidal-Puig A, Vallier L, Nair KS, Wareham NJ, Ron D, Gribble FM, Reimann F, Sattar N, Savage DB, Allan BB, O’Rahilly S. GDF15 mediates the effects of metformin on body weight and energy balance. Nature. 2019 Dec 25. doi: 10.1038/s41586-019-1911-y. [Epub ahead of print] PubMed PMID: 31875646.
Patel S, Alvarez-Guaita A, Melvin A, Rimmington D, Dattilo A, MiedzybrodzkaEL, Cimino I, Maurin AC, Roberts GP, Meek CL, Virtue S, Sparks LM, Parsons SA,Redman LM, Bray GA, Liou AP, Woods RM, Parry SA, Jeppesen PB, Kolnes AJ, Harding HP, Ron D, Vidal-Puig A, Reimann F, Gribble FM, Hulston CJ, Farooqi IS,Fafournoux P, Smith SR, Jensen J, Breen D, Wu Z, Zhang BB, Coll AP, Savage DB, O’Rahilly S. GDF15 Provides an Endocrine Signal of Nutritional Stress in Mice and Humans. Cell Metab. 2019 Mar 5;29(3):707-718.e8. doi: 10.1016/j.cmet.2018.12.016. Epub 2019 Jan 10. PubMed PMID: 30639358; PubMed Central PMCID: PMC6408327.
Polex-Wolf J, Lam BY, Larder R, Tadross J, Rimmington D, Bosch F, Cenzano VJ, Ayuso E, Ma MK, Rainbow K, Coll AP, O’Rahilly S, Yeo GS. Hypothalamic loss of Snord116 recapitulates the hyperphagia of Prader-Willi syndrome. J Clin Invest. 2018 Jan 29. pii: 97007. doi: 10.1172/JCI97007. [Epub ahead of print] PubMed PMID: 29376887.
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 Aca Sci U S A. 2017 Aug 29;114(35):9421-9426. PMID: 28811369. PMCID: PMC558443.
Lam BYH, Cimino I, Polex-Wolf J, Nicole Kohnke S, Rimmington D, Iyemere V, Heeley N, Cossetti C, Schulte R, Saraiva LR, Logan DW, Blouet C, O’Rahilly S, Coll AP, Yeo GSH. Heterogeneity of hypothalamic pro-opiomelanocortin-expressing neurons revealed by single-cell RNA sequencing. Mol Metab. 2017 Mar 1;6(5):383-392. PMID: 28462073; PMCID: PMC5404100.