Professor Giles Yeo MBE University positionProfessor Professor Giles Yeo MBE is pleased to consider applications from prospective PhD students. DepartmentsDepartment of Clinical Biochemistry InstitutesInstitute of Metabolic Science Home pagehttp://www.mrl.ims.cam.ac.uk/researc... (personal home page) Research ThemeInterestsI study brain control of body-weight, and currently have two main aims: Identifying new players in the hypothalamic control of energy balance. a. Genetic studies point to the brain as having a crucial role in modulating appetitive behaviour. A collaboration with the Cambridge Brain Bank allowing us access to human donor brain samples, coupled with ‘dropseq’ single-cell sequencing technologies and single-molecule FISH, provides us an opportunity to map the functional architecture of the human hypothalamus underlying appetitive behaviour. b. Understanding the physiological role of known genetic modifiers influencing food intake and body-weight. Drosophila has been demonstrated to be an excellent in vivo model for dissecting metabolic homeostasis pathways. We have developed a suite of assays to examine changes in the state of energy homeostasis and food intake. We are also currently interested the role of the non-coding RNAs Snord116 in the aetiology of Prader-Willi Syndrome (PWS).  Laser captured mouse hypothalamic nuclei Click image to view full-size Research Focus
EquipmentBioinformatics Cell culture Confocal microscopy Cross-sectional and cohort studies Gene expression profiling High-throughput 'next-gen' sequencing Laser capture microdissection Collaborators
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Key publicationsGulati 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 (2013), “Role for the obesity-related FTO gene in the cellular sensing of amino acids.” Proc Natl Acad Sci U S A 110(7):2557-62 Details Jovanovic Z, Tung YC, Lam BY, O'Rahilly S, Yeo GS (2010), “Identification of the global transcriptomic response of the hypothalamic arcuate nucleus to fasting and leptin.” J Neuroendocrinol 22(8):915-25 Details Tung YC, Ayuso E, Shan X, Bosch F, O'Rahilly S, Coll AP, Yeo GS (2010), “Hypothalamic-specific manipulation of Fto, the ortholog of the human obesity gene FTO, affects food intake in rats.” PLoS One 5(1):e8771 PDF Details Tung YC, Ma M, Piper S, Coll A, O'Rahilly S, Yeo GS (2008), “Novel leptin-regulated genes revealed by transcriptional profiling of the hypothalamic paraventricular nucleus.” J Neurosci 28(47):12419-26 Details Yeo GSH, Hung CC, Rochford J, Keogh JM, Gray J, Sivaramakrishnan S, O’Rahilly S, Farooqi IS (2004), “A de novo mutation affecting human TrkB associated with severe obesity and developmental delay” Nature Neuroscience 7(11):1187-9 Publications2014Carr SK, Chen JH, Cooper WN, Constância M, Yeo GS, Ozanne SE (2014), “Maternal diet amplifies the hepatic aging trajectory of Cidea in male mice and leads to the development of fatty liver.” FASEB J Details Loos RJ, Yeo GS (2014), “The bigger picture of FTO--the first GWAS-identified obesity gene.” Nat Rev Endocrinol 10(1):51-61 Details Moshayedi P, Ng G, Kwok JC, Yeo GS, Bryant CE, Fawcett JW, Franze K, Guck J (2014), “The relationship between glial cell mechanosensitivity and foreign body reactions in the central nervous system.” Biomaterials Details 2013Azizan EA, Poulsen H, Tuluc P, Zhou J, Clausen MV, Lieb A, Maniero C, Garg S, Bochukova EG, Zhao W, Shaikh LH, Brighton CA, Teo AE, Davenport AP, Dekkers T, Tops B, Küsters B, Ceral J, Yeo GS, Neogi SG, McFarlane I, Rosenfeld N, Marass F, Hadfield J, Margas W, Chaggar K, Solar M, Deinum J, Dolphin AC, Farooqi IS, Striessnig J, Nissen P, Brown MJ (2013), “Somatic mutations in ATP1A1 and CACNA1D underlie a common subtype of adrenal hypertension.” Nat Genet 45(9):1055-60 Details Cheung MK, Gulati P, O'Rahilly S, Yeo GS (2013), “FTO expression is regulated by availability of essential amino acids.” Int J Obes (Lond) 37(5):744-7 Details Coll AP, Yeo GS (2013), “The hypothalamus and metabolism: integrating signals to control energy and glucose homeostasis.” Curr Opin Pharmacol 13(6):970-6 Details Goodall JC, Yeo GS (2013), “PP2Ce: Fat and stressed out?” Mol Metab 2(4):325-6 Details Gulati P, Yeo GS (2013), “The biology of FTO: from nucleic acid demethylase to amino acid sensor.” Diabetologia 56(10):2113-21 Details 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 (2013), “Adult onset global loss of the fto gene alters body composition and metabolism in the mouse.” PLoS Genet 9(1):e1003166 Details 2012Chadt A, Yeo GS, Al-Hasani H (2012), “Nutrition-/diet-induced changes in gene expression in pancreatic ?-cells.” Diabetes Obes Metab 14 Suppl 3:57-67 Details Habib AM, Richards P, Cairns LS, Rogers GJ, Bannon CA, Parker HE, Morley TC, Yeo GS, Reimann F, Gribble FM (2012), “Overlap of endocrine hormone expression in the mouse intestine revealed by transcriptional profiling and flow cytometry.” Endocrinology 153(7):3054-65 Details Klus P, Lam S, Lyberg D, Cheung MS, Pullan G, McFarlane I, Yeo GSh, Lam BY (2012), “BarraCUDA - a fast short read sequence aligner using graphics processing units.” BMC Res Notes 5:27 Details Ma M, Harding HP, O'Rahilly S, Ron D, Yeo GS (2012), “Kinetic analysis of FTO (fat mass and obesity-associated) reveals that it is unlikely to function as a sensor for 2-oxoglutarate.” Biochem J 444(2):183-7 Details Yeo GS (2012), “FTO and obesity: a problem for a billion people.” J Neuroendocrinol 24(2):393-4 Details Yeo GS, Heisler LK (2012), “Unraveling the brain regulation of appetite: lessons from genetics.” Nat Neurosci 15(10):1343-9 Details Yeo GS, O'Rahilly S (2012), “Uncovering the biology of FTO.” Mol Metab 1(1-2):32-6 Details Zito E, Hansen HG, Yeo GS, Fujii J, Ron D (2012), “Endoplasmic reticulum thiol oxidase deficiency leads to ascorbic acid depletion and noncanonical scurvy in mice.” Mol Cell 48(1):39-51 Details 2011Cheung MK, Yeo GS (2011), “FTO Biology and Obesity: Why Do a Billion of Us Weigh 3 kg More?” Front Endocrinol (Lausanne) 2:4 Details Gumy LF, Yeo GS, Tung YC, Zivraj KH, Willis D, Coppola G, Lam BY, Twiss JL, Holt CE, Fawcett JW (2011), “Transcriptome analysis of embryonic and adult sensory axons reveals changes in mRNA repertoire localization.” RNA 17(1):85-98 Details Larder R, Cheung MK, Tung YC, Yeo GS, Coll AP (2011), “Where to go with FTO?” Trends Endocrinol Metab 22(2):53-9 Details Shan X, Yeo GS (2011), “Central leptin and ghrelin signalling: comparing and contrasting their mechanisms of action in the brain.” Rev Endocr Metab Disord 12(3):197-209 Details Stewart L, Hindmarch CC, Qiu J, Tung YC, Yeo GS, Murphy D (2011), “Hypothalamic transcriptome plasticity in two rodent species reveals divergent differential gene expression but conserved pathways.” J Neuroendocrinol 23(2):177-85 Details Tung YC, Yeo GS (2011), “From GWAS to biology: lessons from FTO.” Ann N Y Acad Sci 1220:162-71 Details Yeo GS (2011), “Where next for GWAS?” Brief Funct Genomics 10(2):51 Details 2010Chen JH, Tarry-Adkins JL, Matharu K, Yeo GS, Ozanne SE (2010), “Maternal protein restriction affects gene expression profiles in the kidney at weaning with implications for the regulation of renal function and lifespan.” Clin Sci (Lond) 119(9):373-84 Details Corander MP, Challis BG, Thompson EL, Jovanovic Z, Loraine Tung YC, Rimmington D, Huhtaniemi IT, Murphy KG, Topaloglu AK, Yeo GS, O'Rahilly S, Dhillo WS, Semple RK, Coll AP (2010), “The effects of neurokinin B upon gonadotrophin release in male rodents.” J Neuroendocrinol 22(3):181-7 Details Dreja T, Jovanovic Z, Rasche A, Kluge R, Herwig R, Tung YC, Joost HG, Yeo GS, Al-Hasani H (2010), “Diet-induced gene expression of isolated pancreatic islets from a polygenic mouse model of the metabolic syndrome.” Diabetologia 53(2):309-20 Details Jovanovic Z, Yeo GS (2010), “Central leptin signalling: beyond the arcuate nucleus.” Auton Neurosci 156(1-2):8-14 Details Meyre D, Proulx K, Kawagoe-Takaki H, Vatin V, Gutiérrez-Aguilar R, Lyon D, Ma M, Choquet H, Horber F, Van Hul W, Van Gaal L, Balkau B, Visvikis-Siest S, Pattou F, Farooqi IS, Saudek V, O'Rahilly S, Froguel P, Sedgwick B, Yeo GS (2010), “Prevalence of loss-of-function FTO mutations in lean and obese individuals.” Diabetes 59(1):311-8 Details Romeo S, Sentinelli F, Dash S, Yeo GS, Savage DB, Leonetti F, Capoccia D, Incani M, Maglio C, Iacovino M, O'Rahilly S, Baroni MG (2010), “Morbid obesity exposes the association between PNPLA3 I148M (rs738409) and indices of hepatic injury in individuals of European descent.” Int J Obes (Lond) 34(1):190-4 Details Tung YC, Yeo GS (2010), “Central melanocortin signaling regulates cholesterol.” Nat Neurosci 13(7):779-80 Details Zivraj KH, Tung YC, Piper M, Gumy L, Fawcett JW, Yeo GS, Holt CE (2010), “Subcellular profiling reveals distinct and developmentally regulated repertoire of growth cone mRNAs.” J Neurosci 30(46):15464-78 Details 2009Boissel S, Reish O, Proulx K, Kawagoe-Takaki H, Sedgwick B, Yeo GS, Meyre D, Golzio C, Molinari F, Kadhom N, Etchevers HC, Saudek V, Farooqi IS, Froguel P, Lindahl T, O'Rahilly S, Munnich A, Colleaux L (2009), “Loss-of-function mutation in the dioxygenase-encoding FTO gene causes severe growth retardation and multiple malformations.” Am J Hum Genet 85(1):106-11 Details Dash S, Sano H, Rochford JJ, Semple RK, Yeo G, Hyden CS, Soos MA, Clark J, Rodin A, Langenberg C, Druet C, Fawcett KA, Tung YC, Wareham NJ, Barroso I, Lienhard GE, O'Rahilly S, Savage DB (2009), “A truncation mutation in TBC1D4 in a family with acanthosis nigricans and postprandial hyperinsulinemia.” Proc Natl Acad Sci U S A 106(23):9350-5 Details de Smith AJ, Purmann C, Walters RG, Ellis RJ, Holder SE, Van Haelst MM, Brady AF, Fairbrother UL, Dattani M, Keogh JM, Henning E, Yeo GS, O'Rahilly S, Froguel P, Farooqi IS, Blakemore AI (2009), “A deletion of the HBII-85 class of small nucleolar RNAs (snoRNAs) is associated with hyperphagia, obesity and hypogonadism.” Hum Mol Genet 18(17):3257-65 Details Tan K, Pogozheva ID, Yeo GS, Hadaschik D, Keogh JM, Haskell-Leuvano C, O'Rahilly S, Mosberg HI, Farooqi IS (2009), “Functional characterization and structural modeling of obesity associated mutations in the melanocortin 4 receptor.” Endocrinology 150(1):114-25 Details 2008Coll AP, Yeo GS, Farooqi IS, O'Rahilly S (2008), “SnapShot: the hormonal control of food intake.” Cell 135(3):572.e1-2 Details Lam DD, Przydzial MJ, Ridley SH, Yeo GS, Rochford JJ, O'Rahilly S, Heisler LK (2008), “Serotonin 5-HT2C receptor agonist promotes hypophagia via downstream activation of melanocortin 4 receptors.” Endocrinology 149(3):1323-8 Details 2007Gerken T, Girard CA, Tung YC, Webby CJ, Saudek V, Hewitson KS, Yeo GS, McDonough MA, Cunliffe S, McNeill LA, Galvanovskis J, Rorsman P, Robins P, Prieur X, Coll AP, Ma M, Jovanovic Z, Farooqi IS, Sedgwick B, Barroso I, Lindahl T, Ponting CP, Ashcroft FM, O'Rahilly S, Schofield CJ (2007), “The obesity-associated FTO gene encodes a 2-oxoglutarate-dependent nucleic acid demethylase.” Science 318(5855):1469-72 Details Goodall JC, Ellis L, Yeo GS, Gaston JS (2007), “Does HLA-B27 influence the monocyte inflammatory response to lipopolysaccharide?” Rheumatology (Oxford) 46(2):232-7 Details Gray J, Yeo G, Hung C, Keogh J, Clayton P, Banerjee K, McAulay A, O'Rahilly S, Farooqi IS (2007), “Functional characterization of human NTRK2 mutations identified in patients with severe early-onset obesity.” Int J Obes (Lond) 31(2):359-64 Details Heisler LK, Pronchuk N, Nonogaki K, Zhou L, Raber J, Tung L, Yeo GS, O'Rahilly S, Colmers WF, Elmquist JK, Tecott LH (2007), “Serotonin activates the hypothalamic-pituitary-adrenal axis via serotonin 2C receptor stimulation.” J Neurosci 27(26):6956-64 Details Medina-Gomez G, Gray SL, Yetukuri L, Shimomura K, Virtue S, Campbell M, Curtis RK, Jimenez-Linan M, Blount M, Yeo GS, Lopez M, Seppänen-Laakso T, Ashcroft FM, Oresic M, Vidal-Puig A (2007), “PPAR gamma 2 prevents lipotoxicity by controlling adipose tissue expandability and peripheral lipid metabolism.” PLoS Genet 3(4):e64 Details Oswal A, Yeo GS (2007), “The leptin melanocortin pathway and the control of body weight: lessons from human and murine genetics.” Obes Rev 8(4):293-306 Details 2006Gray J, Yeo GS, Cox JJ, Morton J, Adlam AL, Keogh JM, Yanovski JA, El Gharbawy A, Han JC, Tung YC, Hodges JR, Raymond FL, O'rahilly S, Farooqi IS (2006), “Hyperphagia, severe obesity, impaired cognitive function, and hyperactivity associated with functional loss of one copy of the brain-derived neurotrophic factor (BDNF) gene.” Diabetes 55(12):3366-71 Details Gray SL, Nora ED, Grosse J, Manieri M, Stoeger T, Medina-Gomez G, Burling K, Wattler S, Russ A, Yeo GS, Chatterjee VK, O'Rahilly S, Voshol PJ, Cinti S, Vidal-Puig A (2006), “Leptin deficiency unmasks the deleterious effects of impaired peroxisome proliferator-activated receptor gamma function (P465L PPARgamma) in mice.” Diabetes 55(10):2669-77 Details Lee YS, Challis BG, Thompson DA, Yeo GS, Keogh JM, Madonna ME, Wraight V, Sims M, Vatin V, Meyre D, Shield J, Burren C, Ibrahim Z, Cheetham T, Swift P, Blackwood A, Hung CC, Wareham NJ, Froguel P, Millhauser GL, O'Rahilly S, Farooqi IS (2006), “A POMC variant implicates beta-melanocyte-stimulating hormone in the control of human energy balance.” Cell Metab 3(2):135-40 Details Pett MR, Herdman MT, Palmer RD, Yeo GS, Shivji MK, Stanley MA, Coleman N (2006), “Selection of cervical keratinocytes containing integrated HPV16 associates with episome loss and an endogenous antiviral response.” Proc Natl Acad Sci U S A 103(10):3822-7 Details 2005Coll AP, Challis BG, López M, Piper S, Yeo GS, O'Rahilly S (2005), “Proopiomelanocortin-deficient mice are hypersensitive to the adverse metabolic effects of glucocorticoids.” Diabetes 54(8):2269-76 Details Lelliott CJ, López M, Curtis RK, Parker N, Laudes M, Yeo G, Jimenez-Liñan M, Grosse J, Saha AK, Wiggins D, Hauton D, Brand MD, O'Rahilly S, Griffin JL, Gibbons GF, Vidal-Puig A (2005), “Transcript and metabolite analysis of the effects of tamoxifen in rat liver reveals inhibition of fatty acid synthesis in the presence of hepatic steatosis.” FASEB J 19(9):1108-19 Details 2004Challis BG, Coll AP, Yeo GS, Pinnock SB, Dickson SL, Thresher RR, Dixon J, Zahn D, Rochford JJ, White A, Oliver RL, Millington G, Aparicio SA, Colledge WH, Russ AP, Carlton MB, O'Rahilly S (2004), “Mice lacking pro-opiomelanocortin are sensitive to high-fat feeding but respond normally to the acute anorectic effects of peptide-YY(3-36).” Proc Natl Acad Sci U S A 101(13):4695-700 Details Coll AP, Challis BG, Yeo GS, Snell K, Piper SJ, Halsall D, Thresher RR, O'Rahilly S (2004), “The effects of proopiomelanocortin deficiency on murine adrenal development and responsiveness to adrenocorticotropin.” Endocrinology 145(10):4721-7 Details Coll AP, Farooqi IS, Challis BG, Yeo GS, O'Rahilly S (2004), “Proopiomelanocortin and energy balance: insights from human and murine genetics.” J Clin Endocrinol Metab 89(6):2557-62 Details Hung CC, Pirie F, Luan J, Lank E, Motala A, Yeo GS, Keogh JM, Wareham NJ, O'Rahilly S, Farooqi IS (2004), “Studies of the peptide YY and neuropeptide Y2 receptor genes in relation to human obesity and obesity-related traits.” Diabetes 53(9):2461-6 Details Laudes M, Barroso I, Luan J, Soos MA, Yeo G, Meirhaeghe A, Logie L, Vidal-Puig A, Schafer AJ, Wareham NJ, O'Rahilly S (2004), “Genetic variants in human sterol regulatory element binding protein-1c in syndromes of severe insulin resistance and type 2 diabetes.” Diabetes 53(3):842-6 Details O'Rahilly S, Yeo GS, Farooqi IS (2004), “Melanocortin receptors weigh in.” Nat Med 10(4):351-2 Details Yeo GS, Connie Hung CC, Rochford J, Keogh J, Gray J, Sivaramakrishnan S, O'Rahilly S, Farooqi IS (2004), “A de novo mutation affecting human TrkB associated with severe obesity and developmental delay.” Nat Neurosci 7(11):1187-9 Details 2003Donohoue PA, Tao YX, Collins M, Yeo GS, O'Rahilly S, Segaloff DL (2003), “Deletion of codons 88-92 of the melanocortin-4 receptor gene: a novel deleterious mutation in an obese female.” J Clin Endocrinol Metab 88(12):5841-5 Details Farooqi IS, Keogh JM, Yeo GS, Lank EJ, Cheetham T, O'Rahilly S (2003), “Clinical spectrum of obesity and mutations in the melanocortin 4 receptor gene.” N Engl J Med 348(12):1085-95 Details Farooqi IS, Yeo GS, O'Rahilly S (2003), “Binge eating as a phenotype of melanocortin 4 receptor gene mutations.” N Engl J Med 349(6):606-9; author reply 606-9 Details Hung CC, Farooqi IS, Ong K, Luan J, Keogh JM, Pembrey M, Yeo GS, Dunger D, Wareham NJ, O' Rahilly S (2003), “Contribution of variants in the small heterodimer partner gene to birthweight, adiposity, and insulin levels: mutational analysis and association studies in multiple populations.” Diabetes 52(5):1288-91 Details Meirhaeghe A, Crowley V, Lenaghan C, Lelliott C, Green K, Stewart A, Hart K, Schinner S, Sethi JK, Yeo G, Brand MD, Cortright RN, O'Rahilly S, Montague C, Vidal-Puig AJ (2003), “Characterization of the human, mouse and rat PGC1 beta (peroxisome-proliferator-activated receptor-gamma co-activator 1 beta) gene in vitro and in vivo.” Biochem J 373(Pt 1):155-65 Details O'Rahilly S, Farooqi IS, Yeo GS, Challis BG (2003), “Minireview: human obesity-lessons from monogenic disorders.” Endocrinology 144(9):3757-64 Details Yeo GS, Lank EJ, Farooqi IS, Keogh J, Challis BG, O'Rahilly S (2003), “Mutations in the human melanocortin-4 receptor gene associated with severe familial obesity disrupts receptor function through multiple molecular mechanisms.” Hum Mol Genet 12(5):561-74 Details Yeo GS, Siddle K (2003), “Attractin' more attention - new pieces in the obesity puzzle?” Biochem J 376(Pt 3):e7-8 Details 2002Berger D, Barroso I, Soos M, Yeo G, Schafer AJ, O'Rahilly S, Whitehead JP (2002), “Genetic variants of insulin receptor substrate-1 (IRS-1) in syndromes of severe insulin resistance. Functional analysis of Ala513Pro and Gly1158Glu IRS-1.” Diabet Med 19(10):804-9 Details Challis BG, Pritchard LE, Creemers JW, Delplanque J, Keogh JM, Luan J, Wareham NJ, Yeo GS, Bhattacharyya S, Froguel P, White A, Farooqi IS, O'Rahilly S (2002), “A missense mutation disrupting a dibasic prohormone processing site in pro-opiomelanocortin (POMC) increases susceptibility to early-onset obesity through a novel molecular mechanism.” Hum Mol Genet 11(17):1997-2004 Details Challis BG, Yeo GS (2002), “Past, present and future strategies to study the genetics of body weight regulation.” Brief Funct Genomic Proteomic 1(3):290-304 Details Crowley VE, Yeo GS, O'Rahilly S (2002), “Obesity therapy: altering the energy intake-and-expenditure balance sheet.” Nat Rev Drug Discov 1(4):276-86 Details Mulligan C, Rochford J, Denyer G, Stephens R, Yeo G, Freeman T, Siddle K, O'Rahilly S (2002), “Microarray analysis of insulin and insulin-like growth factor-1 (IGF-1) receptor signaling reveals the selective up-regulation of the mitogen heparin-binding EGF-like growth factor by IGF-1.” J Biol Chem 277(45):42480-7 Details 2000Challis BG, Yeo GS, Farooqi IS, Luan J, Aminian S, Halsall DJ, Keogh JM, Wareham NJ, O'Rahilly S (2000), “The CART gene and human obesity: mutational analysis and population genetics.” Diabetes 49(5):872-5 Details Farooqi IS, Yeo GS, Keogh JM, Aminian S, Jebb SA, Butler G, Cheetham T, O'Rahilly S (2000), “Dominant and recessive inheritance of morbid obesity associated with melanocortin 4 receptor deficiency.” J Clin Invest 106(2):271-9 Details Yeo GS, Farooqi IS, Challis BG, Jackson RS, O'Rahilly S (2000), “The role of melanocortin signalling in the control of body weight: evidence from human and murine genetic models.” QJM 93(1):7-14 Details 1999Elgar G, Clark MS, Meek S, Smith S, Warner S, Edwards YJ, Bouchireb N, Cottage A, Yeo GS, Umrania Y, Williams G, Brenner S (1999), “Generation and analysis of 25 Mb of genomic DNA from the pufferfish Fugu rubripes by sequence scanning.” Genome Res 9(10):960-71 Details 1998Yeo GS, Farooqi IS, Aminian S, Halsall DJ, Stanhope RG, O'Rahilly S (1998), “A frameshift mutation in MC4R associated with dominantly inherited human obesity.” Nat Genet 20(2):111-2 Details 1997Yeo GS, Elgar G, Sandford R, Brenner S (1997), “Cloning and sequencing of complement component C9 and its linkage to DOC-2 in the pufferfish Fugu rubripes.” Gene 200(1-2):203-11 Details |