Professor Li ChanProfessor of Molecular Endocrinology and Metabolism, Honorary Consultant in Paediatric EndocrinologyCentre: Endocrinology Email: l.chan@qmul.ac.uk Telephone: +44(0) 20 7882 6241Twitter: @LChan_3ProfileResearchKey PublicationsSponsorsCollaboratorsProfileORCID iD: 0000-0001-5146-8242 Professor Li Chan studied Medicine at Cambridge before undertaking her basic paediatric training at Barts and the London Hospitals. She first joined the Centre for Endocrinology in 2005 to undertake her PhD investigating a novel receptor trafficking protein MRAP2 (melanocortin receptor accessory protein two). This was funded by a Barts and the London Charity clinical training fellowship and then an MRC clinical research training fellowship. Her work on the melanocortin receptor accessory proteins MRAP and MRAP2 as regulators of the melanocortin receptor family has revealed important novel aspects of melanocortin receptor biology. During this time she also contributed to two other areas of research: phenotype/genotype analysis of patients with Familial Glucocorticoid Deficiency (FGD), and the long-term follow-up of paediatric Cushing’s disease patients. After her PhD she was awarded the only national GRID training post in Paediatric Endocrinology. She was awarded a Tenure-track MRC/Academy of Medical Sciences clinician scientist fellowship to study the effects of MRAPs in energy homeostasis and adrenal function. She was a visiting scientist at the Sanger Institute and Institute of Metabolic Sciences in Cambridge. In 2012, she was awarded the Journal of Endocrinology outstanding young researcher prize. She was one of 20 female academics to participate in the first SUSTAIN Academy of Medical Sciences Leadership Programme and promoted to Clinical Senior Lecturer in Paediatric Endocrinology. In 2017, she joined the Department of Comparative Medicine at Yale School of Medicine as a visiting Associate Professor for a 6 month period. She is Senior Editor for Endocrine Connections, co-lead for the new Lifelong Health (LHH) multidisciplinary faculty of medicine theme at QMUL, co-lead for GeCiP endocrinology and metabolism domain and GOSH Charity’s Research Assessment Panel member. ResearchGroup members D Jackson, C Lai, N Nguyen, R Xu, D Popat, C Smith (with Prof Metherell) Summary Melanocortin receptor accessory proteins (MRAPs) in adrenal function and energy homeostasisThe MRAPs contribute in major ways to adrenal function and metabolism. Recently they have been shown to be promiscuous accessory factors, with multiple previously unsuspected roles regulating other G protein-coupled receptors beyond the melanocortin receptor family. The structure, function and regulation of these unique anti-parallel accessory factors and their importance in normal physiology and disease states forms one of the main research themes of our laboratory. Familial Glucocorticoid Deficiency (FGD) and Paediatric disorders of the HPA axis and cortisol actionThe Chan laboratory has a long-standing collaboration with Prof Metherell investigating molecular mechanisms and clinical phenotypes in FGD. More broadly, we are interested in clinical conditions affecting the hypothalamic-pituitary-adrenal axis in childhood. The melanocortin system forms a critical component of this axis, hence establishing the molecular regulation of this system promises to highlight future therapeutic targets. The development of MC2R antagonistsTogether with MRC-Technology (now Life-Arc) we have identified small molecule antagonists to MC2R, which would be important for the treatment of conditions of ACTH excess. Key Publications Full list of publications Overexpression of melanocortin 2 receptor accessory protein 2 (MRAP2) in adult paraventricular MC4R neurons regulates energy intake and expenditure. Bruschetta G, Kim JD, Diano S, Chan LF. Mol Metab. 2018 Dec;18:79-87. doi: 10.1016/j.molmet.2018.09.010. Epub 2018 Oct 4. MRAP deficiency impairs adrenal progenitor cell differentiation and gland zonation. Novoselova TV, Hussain M, King PJ, Guasti L, Metherell LA, Charalambous M, Clark AJL, Chan LF. FASEB J. 2018 Jun 7:fj201701274RR. doi: 10.1096/fj.201701274RR. [Epub ahead of print] PMID: 29879378 Novoselova TV, Larder R, Rimmington D, Lelliott C, Wynn EH, Gorrigan RJ, Tate PH, Guasti L, Sanger Mouse Genetics P, O'Rahilly S, Clark AJ, Logan DW, Coll AP, & Chan LF (2016) Loss of Mrap2 is associated with Sim1 deficiency and increased circulating cholesterol. J Endocrinol 230(1):13-26. Samuelsson AS, Mullier A, Maicas N, Oosterhuis NR, Eun Bae S, Novoselova TV, Chan LF, Pombo JM, Taylor PD, Joles JA, Coen CW, Balthasar N, & Poston L (2016) Central role for melanocortin-4 receptors in offspring hypertension arising from maternal obesity. Proc Natl Acad Sci U S A 113(43):12298-12303. Chan LF, Campbell DC, Novoselova TV, Clark AJ, & Metherell LA (2015) Whole-Exome Sequencing in the Differential Diagnosis of Primary Adrenal Insufficiency in Children. Front Endocrinol (Lausanne) 6:113. Asai M, Ramachandrappa S, Joachim M, Shen Y, Zhang R, Nuthalapati N, Ramanathan V, Strochlic DE, Ferket P, Linhart K, Ho C, Novoselova TV, Garg S, Ridderstrale M, Marcus C, Hirschhorn JN, Keogh JM, O'Rahilly S, Chan LF, Clark AJ, Farooqi IS, & Majzoub JA (2013) Loss of function of the melanocortin 2 receptor accessory protein 2 is associated with mammalian obesity. Science 341(6143):275-278. Gorrigan RJ, Guasti L, King P, Clark AJ, & Chan LF (2011) Localisation of the melanocortin-2-receptor and its accessory proteins in the developing and adult adrenal gland. J Mol Endocrinol 46(3):227-232. Chan LF, Webb TR, Chung TT, Meimaridou E, Cooray SN, Guasti L, Chapple JP, Egertova M, Elphick MR, Cheetham ME, Metherell LA, & Clark AJ (2009) MRAP and MRAP2 are bidirectional regulators of the melanocortin receptor family. Proc Natl Acad Sci U S A 106(15):6146-6151. Sponsors Wellcome Trust Medical Research Council International Fund Congenital Adrenal Hyperplasia Barts Charity British Society for Paediatric Endocrinology and Diabetes EU CollaboratorsInternalDr Caroline Brennan; Professor Leo Guasti; Dr Peter McCormick; Professor Lou Metherell; Professor Paul Chapple (WHRI) ExternalDr Tony Coll (University of Cambridge); Prof Stephen O'Rahilly (University of Cambridge); Dr Giles Yeo (University of Cambridge); MRC Technology/LifeArc, Dr Marika Charalambous (King’s College, London), Prof Sabrina Diano & Prof Tamas Horvath (Yale University), Prof Joe Majzoub (Boston Children’s) Back to top
Full list of publications Overexpression of melanocortin 2 receptor accessory protein 2 (MRAP2) in adult paraventricular MC4R neurons regulates energy intake and expenditure. Bruschetta G, Kim JD, Diano S, Chan LF. Mol Metab. 2018 Dec;18:79-87. doi: 10.1016/j.molmet.2018.09.010. Epub 2018 Oct 4. MRAP deficiency impairs adrenal progenitor cell differentiation and gland zonation. Novoselova TV, Hussain M, King PJ, Guasti L, Metherell LA, Charalambous M, Clark AJL, Chan LF. FASEB J. 2018 Jun 7:fj201701274RR. doi: 10.1096/fj.201701274RR. [Epub ahead of print] PMID: 29879378 Novoselova TV, Larder R, Rimmington D, Lelliott C, Wynn EH, Gorrigan RJ, Tate PH, Guasti L, Sanger Mouse Genetics P, O'Rahilly S, Clark AJ, Logan DW, Coll AP, & Chan LF (2016) Loss of Mrap2 is associated with Sim1 deficiency and increased circulating cholesterol. J Endocrinol 230(1):13-26. Samuelsson AS, Mullier A, Maicas N, Oosterhuis NR, Eun Bae S, Novoselova TV, Chan LF, Pombo JM, Taylor PD, Joles JA, Coen CW, Balthasar N, & Poston L (2016) Central role for melanocortin-4 receptors in offspring hypertension arising from maternal obesity. Proc Natl Acad Sci U S A 113(43):12298-12303. Chan LF, Campbell DC, Novoselova TV, Clark AJ, & Metherell LA (2015) Whole-Exome Sequencing in the Differential Diagnosis of Primary Adrenal Insufficiency in Children. Front Endocrinol (Lausanne) 6:113. Asai M, Ramachandrappa S, Joachim M, Shen Y, Zhang R, Nuthalapati N, Ramanathan V, Strochlic DE, Ferket P, Linhart K, Ho C, Novoselova TV, Garg S, Ridderstrale M, Marcus C, Hirschhorn JN, Keogh JM, O'Rahilly S, Chan LF, Clark AJ, Farooqi IS, & Majzoub JA (2013) Loss of function of the melanocortin 2 receptor accessory protein 2 is associated with mammalian obesity. Science 341(6143):275-278. Gorrigan RJ, Guasti L, King P, Clark AJ, & Chan LF (2011) Localisation of the melanocortin-2-receptor and its accessory proteins in the developing and adult adrenal gland. J Mol Endocrinol 46(3):227-232. Chan LF, Webb TR, Chung TT, Meimaridou E, Cooray SN, Guasti L, Chapple JP, Egertova M, Elphick MR, Cheetham ME, Metherell LA, & Clark AJ (2009) MRAP and MRAP2 are bidirectional regulators of the melanocortin receptor family. Proc Natl Acad Sci U S A 106(15):6146-6151.