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.
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.
Mountjoy KG, Caron A, Hubbard K, Shome A, Grey AC, Sun B, Bould S, Middledditch M, Pontré B, McGregor A, Harris PWR, Kowalczyk R, Brimble MA, Botha R, Tan KML, Piper SJ, Buchanan C, Lee S, Coll AP, Elmquist JK. Desacetyle-α-melanocyte stimulating hormone and α-melanocyte stimulating hormone are required to regulate energy balance. Mol Metab. 2017 Nov 24. pii: S2212-8778(17)30819-o. doi: 10.1016/j.molmet.2017.11.008. [Epub ahead of print] PubMed PMID: 29226825.
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.
Flint TR, Janowitz T, Connell CM, Roberts EW, Denton AE, Coll AP, Jodell DI, Fearon DT. Tumor-Induced IL-6 Reprograms Host Metabolism to Suppress Anti-tumor Immunity. Cell Metab. 2016 Nov 8;24(5):672-684. PMID 27829137. PMC51006372.