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Institute of Metabolic Science

Metabolic Research Laboratories
 

Professor Sadaf Farooqi

Research Vision 

Our goal is to develop new treatments for people living with severe obesity by delivering a step-change in our understanding of the control of human energy balance. 

Severe Childhood Obesity 

We have shown that mutations disrupting the hormone leptin and its downstream neural targets cause hyperphagia and severe childhood obesity. With the help of many international collaborators, we have recruited over 7000 people with severe childhood onset obesity to the Genetics of Obesity Study (GOOS). We identify networks of genes and the molecular mechanisms they perturb and undertake physiological studies to determine how these molecules affect eating behaviour and energy expenditure. In this work, we benefit hugely from the Translational Research Facility (TRF)  LINK  to TRF page once live on our website 

Thinness 

We are also interested in understanding how and why some people remain thin in an obesogenic environment. Thinness (BMI<18kg/m2) is as heritable as severe obesity. We have recruited a UK cohort of 4000 thin people (STILTS cohort) in whom we are undertaking genetic and physiological studies. 

Translational Research 

We have developed new diagnostics for a range of obesity syndromes and an NHS Obesity Gene Panel is now available for use by Physicians in the UK. We treat patients with congenital leptin deficiency from around the world. We are running clinical trials administering Setmelanotide (a melanocortin 4 receptor agonist) in patients with several genetic obesity syndromes and work with other companies in drug discovery and trials. 

Secretary

Ms Jacqui Brocker  - jb682 at medschl.cam.ac.uk

 

The Society for Endocrinology  awarded Ming Lin, who was a visiting student with the Farooqi group for summer 2024, with a Society for Endocrinology Teaching Grant.

 

Group Members 

Dr Rebecca Bounds, Senior Research Co-ordinator  - rb620 at medschl.cam.ac.uk  

Mrs Elana Henning, Senior Research Nurse  - eh330 at cam.ac.uk  

Dr Isabel Huang-Doran, Wellcome Clinical Career Development Fellow  - ih240 at medschl.cam.ac.uk  

Dr Katherine Lawler, Postdoctoral Research Associate - kl229 at medschl.cam.ac.uk  

Dr Robert Legg, Clinical Fellow in Genetics - rgl28 at medschl.cam.ac.uk  

Dr Kevin Manuel Mendez Acevedo, Postdoctoral Research Associate - Kmm87 at medschl.cam.ac.uk  

Mrs Angela Reynolds, Data Manager - ar722 at medschl.cam.ac.uk  

Dr Jacopo Scotucci, Clinical Research Associate - js2604 at medschl.cam.ac.uk 

Dr Dinesh Shah, Postdoctoral Research Associate - dss57 at medschl.cam.ac.uk  

Dr Miriam Smith, Research Co-ordinator - ms2515 at medschl.cam.ac.uk  

Miss Lynne Stanley, Research Study Coordinator  - ls824 at medschl.cam.ac.uk  

Dr Agatha Van der Klaauw, Senior Clinical Research Associate - av330 at medschl.cam.ac.uk  

Funding 

Wellcome Trust 

NIHR Cambridge Biomedical Research Centre 

NIHR Senior Investigator Award 

Botnar Foundation 

Bernard Wolfe Endowment 

Leducq Foundation 

Publications

Key publications: 

Farooqi IS, Xu Y. Translational potential of mouse models of human metabolic disease. Cell. 2024 July; PMID: 39067442. 

Li Y, Cacciottolo TM, Yin N, He Y, Liu H, Liu H, Yang Y, Henning E, Keogh JM, Lawler K, Mendes de Oliveira E, Gardner EJ, Kentistou KA, Laouris P, Bounds R, Ong KK, Perry JRB, Barroso I, Tu L, Bean JC, Yu M, Conde KM, Wang M, Ginnard O, Fang X, Tong L, Han J, Darwich T, Williams KW, Yang Y, Wang C, Joss S, Firth HV, Xu Y, Farooqi IS. Loss of transient receptor potential channel 5 causes obesity and postpartum depression. Cell. 2024 Jun; PMID: 38959890. 

van der Klaauw AA, Horner EC, Pereyra-Gerber P, Agrawal U, Foster WS, Spencer S, Vergese B, Smith M, Henning E, Ramsay ID, Smith JA, Guillaume SM, Sharpe HJ, Hay IM, Thompson S, Innocentin S, Booth LH, Robertson C, McCowan C, Kerr S, Mulroney TE, O'Reilly MJ, Gurugama TP, Gurugama LP, Rust MA, Ferreira A, Ebrahimi S, Ceron-Gutierrez L, Scotucci J, Kronsteiner B, Dunachie SJ, Klenerman P; PITCH Consortium; Park AJ, Rubino F, Lamikanra AA, Stark H, Kingston N, Estcourt L, Harvala H, Roberts DJ, Doffinger R, Linterman MA, Matheson NJ, Sheikh A, Farooqi IS, Thaventhiran JED. Accelerated waning of the humoral response to COVID-19 vaccines in obesity. Nat Med. 2023 May; PMID: 37169862; PMCID: PMC10202802. 

Talbot F, Feetham CH, Mokrosiński J, Lawler K, Keogh JM, Henning E, Mendes de Oliveira E, Ayinampudi V, Saeed S, Bonnefond A, Arslan M, Yeo GSH, Froguel P, Bechtold DA, Adamson A, Humphreys N, Barroso I, Luckman SM, Farooqi IS. A rare human variant that disrupts GPR10 signalling causes weight gain in mice. Nat Commun. 2023 Mar 15;14(1):1450. doi: 10.1038/s41467-023-36966-3. PMID: 36922513; PMCID: PMC10017677. 

He Y, Brouwers B, Liu H, Liu H, Lawler K, Mendes de Oliveira E, Lee DK, Yang Y, Cox AR, Keogh JM, Henning E, Bounds R, Perdikari A, Ayinampudi V, Wang C, Yu M, Tu L, Zhang N, Yin N, Han J, Scarcelli KA, Yan Z, Conde KM, Potts C, Bean JC, Wang M, Hartig SM, Liao L, Xu J, Barroso I, Mokrosinski J, Xu Y, Farooqi SI. Human loss-of-function variants in the Serotonin 2C receptor associated with obesity and maladaptive behaviour. Nature Medicine 2022 Dec 19; PMID: 36536256. 

Mendes de Oliveira E, Keogh JM, Talbot F, Henning E, Ahmed R, Perdikari A, Bounds R, Wasiluk N, Ayinampudi V, Barroso I, Mokrosiński J, Jyothish D, Lim S, Gupta S, Kershaw M, Matei C, Partha P, Randell T, McAculay A, Wilson LC, Cheetham T, Crowne EC, Clayton P, Farooqi IS, Obesity-Associated GNAS Mutations and the Melanocortin Pathway. New England Journal of Medicine, 2021 October; PMID: 34614324 

Lotta LA, Mokrosiński J, Mendes de Oliveira E, Li C, Sharp SJ, Luan J, Brouwers B, Ayinampudi V, Bowker N, Kerrison N, Kaimakis V, Hoult D, Stewart ID, Wheeler E, Day FR, Perry JRB, Langenberg C, Wareham NJ, Farooqi IS. Human Gain-of-Function MC4R Variants Show Signaling Bias and Protect against Obesity  Cell. 2019 Apr 18;177(3):597-607.e9. doi: 10.1016/j.cell.2019.03.044 

Riveros-McKay F, Mistry V, Bounds R, Hendricks A, Keogh JM, Thomas H, Henning E, Corbin LJ; Understanding Society Scientific Group, O’Rahilly S, Zeggini E, Wheeler E, Barroso I, Farooqi IS. Genetic architecture of human thinness compared to severe obesity. PLoS Genet. 2019 Jan 24;15(1):e1007603. doi: 10.1371/journal.pgen.1007603. 

Wellcome Trust Principal Research Fellow 
Professor of Metabolism and Medicine
Department of Clinical Biochemistry, University of Cambridge
photo of sadaf farooqi
Collaborator profiles: 
Professor Sir Stephen O'Rahilly
Classifications: 
Principal Investigators

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Research at Cambridge