Research Interests
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 disorders of energy balance and metabolism
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. Through an evolving interaction with colleagues at CRUK , I am also interested in determining how resources and skills developed in the study of obesity can be employed to understand the body composition and metabolic phenoptypes see in cachexia.
Selected Publications
Cimino I, Rimmington D, Tung YCL, Lawler K, Larraufie P, Kay RG, Virtue S, Lam BYH, Fagnocchi L, Ma MKL, Saudek V, Zvetkova I, Vidal-Puig A, Yeo GSH, Farooqi IS, Pospisilik JA, Gribble FM, Reimann F, O’Rahilly S, Coll AP. Murine neuronatin deficiency is associated with a hypervariable food intake and bimodal obesity. Sci Rep. 2021 Sep 2;11(1):17571. doi: 10.1038/s41598-021-96278-8. PMID: 34475432; PMCID: PMC8413370.
Cimino I, Kim H, Tung YCL, Pedersen K, Rimmington D, Tadross JA, Kohnke SN, Neves-Costa A, Barros A, Joaquim S, Bennett D, Melvin A, Lockhart SM, Rostron AJ, Scott J, Liu H, Burling K, Barker P, Clatworthy MR, Lee EC, Simpson AJ, Yeo GSH, Moita LF, Bence KK, Jørgensen SB, Coll AP, Breen DM, O’Rahilly S. Activation of the hypothalamic-pituitary-adrenal axis by exogenous and endogenous GDF15. Proc Natl Acad Sci U S A. 2021 Jul 6;118(27):e2106868118. doi: 10.1073/pnas.2106868118. PMID: 34187898; PMCID: PMC8271778.
Trappc9 deficiency causes parent-of-origin dependent microcephaly and obesity. Liang ZS, Cimino I, Yalcin B, Raghupathy N, Vancollie VE, Ibarra-Soria X, Firth HV, Rimmington D, Farooqi IS, Lelliott CJ, Munger SC, O’Rahilly S, Ferguson-Smith AC, Coll AP, Logan DW. PLoS Genet. 2020 Sep 2;16(9):e1008916. doi: 10.1371/journal.pgen.1008916. eCollection 2020 Sep. PMID: 32877400. PMCID: PMC7467316
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. PMCID: PMC7234839
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; 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. PMCID: PMC5824864
