Chan, Li

Dr Li Chan

Clinical Research Fellow

Dr Li Chan studied Medicine at Cambridge before undertaking her basic paediatric training at Barts and the London Hospitals. During this time she undertook research studying the insulin-like growth factor-1 and growth hormone receptor gene in small for gestational age infants in Prof. Martin Savage and Prof. Adrian Clark’s team and worked as a member of the NESTEGG (Northern European Study of Genes in Growth) team. In 2005 she was awarded a clinical training fellowship funded by the Barts and the London Charity and subsequently she gained an MRC clinical research training fellowship, which enabled her to complete her PhD investigating a novel receptor trafficking protein MRAP2 (melanocortin receptor accessory protein two). Her work on melanocortin receptor accessory proteins, MRAP and MRAP2, as regulators of the melanocortin receptor family has revealed important novel aspects of melanocortin receptor biology. She was awarded the Society for Endocrinology Young Investigator prize in 2008 based on this work, and is recipient of a Novo-Nordisk educational award as well as a Clinician-Scientist in Training prize in Endocrinology. During this time she was also involved with two other areas of research: the mutational analysis of patients with Familial Glucocorticoid Deficiency, and the long-term follow-up of paediatric Cushing’s disease patients.

After her PhD she succeeded in obtaining the only national GRID training post in Paediatric Endocrinology in 2008. The following year she was awarded a 5 year tenure-track MRC/Academy of Medical Sciences clinician scientist fellowship to build on existing work and study the effects of melanocortin receptor accessory proteins in energy homeostasis and adrenal function. In 2012 she was awarded the Journal of Endocrinology outstanding young researcher prize.

Summary of Research

The role of melanocortin receptor accessory proteins (MRAPs) in physiology and disease

I am primarily interested in clinical conditions affecting the hypothalamic-pituitary-adrenal axis in childhood. The melanocortin system forms a critical component of the axis hence establishing the molecular regulation of this system will highlight future therapeutic targets.

Ongoing research
MRAP was discovered in 2005 as the second cause of a rare autosomal recessive clinical condition FGD type 2. This protein, which forms a unique antiparallel homodimer, was shown to be essential in the trafficking of the MC2R to the cell surface to allow normal functioning. MRAP2, a paralogue of MRAP is predominantly expressed in the brain and hypothalamus. Both MRAPs are expressed beyond the adrenal gland and have been shown to interact and regulate other melanocortin receptors in-vitro. The aim of my research is to establish the role of MRAPs in the regulation of other melanocortin receptors and/or GPCRs, and their contribution to normal physiology and disease processes.

In situ hybridisation showing localisation of Mrap, Mrap2 and Mc2r in foetal [A-G] and adult Wistar

In situ hybridisation showing localisation of Mrap, Mrap2 and Mc2r in foetal [A-G] and adult Wistar rat adrenal glands [H-N]. [A]&[E] Foetal rat adrenal expression of MRAP and MRAP2 respectively, magnified in [C], [D]. Sense riboprobes (S); adrenal capsule (C); subcapsular zone (indicated by T). [G] Cells positive for Mrap also express CYP11B1. [H]-[K] In the adult adrenal gland Mc2r and Mrap are present in the zona fasciculata (ZF), with relative sparing of the capsule, zona glomerulosa (ZG) and medulla (M). [L] Mc2r is also expressed highly in the undifferentiated zone (ZU), in cells which lack CYP11B1 expression. [M] Mrap2 is expressed at low levels throughout the adult rat adrenal gland. Images from Gorrigan et al. JME, 2011.

Members of the Group

Research Staff: Tatiana Novoselova; Rebecca Gorrigan; Mashal Hussain.

Key Publications

For a full list of publist publications click here
 
Gorrigan RJ, Guasti L, King P et al. (2011). Localisation of the melanocortin-2-receptor and its accessory proteins in the developing and adult adrenal gland.. J Mol Endocrinol Vol.46, (3) 227-232. 10.1530/JME-11-0011

Chan LF, Webb TR, Chung TT et al. (2009). MRAP and MRAP2 are bidirectional regulators of the melanocortin receptor family.. Proc Natl Acad Sci USA Vol.106, (15) 6146-6151. 10.1073/pnas.0809918106

Chan LF, Chung TT, Massoud AF et al. (2009). Functional consequence of a novel Y129C mutation in a patient with two contradictory melanocortin-2-receptor mutations.. Eur J Endocrinol Vol.160, (4) 705-710. 10.1530/EJE-08-0636

Webb TR, Chan L, Cooray SN et al. (2009). Distinct melanocortin 2 receptor accessory protein domains are required for melanocortin 2 receptor interaction and promotion of receptor trafficking. 10.1210/en.2008-0941

Chan LF, Metherell LA, Krude H et al. (2009). Homozygous nonsense and frameshift mutations of the ACTH receptor in children with familial glucocorticoid deficiency (FGD) are not associated with long-term mineralocorticoid deficiency. Clin Endocrinol (Oxf) Vol.71, (2) 1365-2265 171-175. 10.1111/j.1365-2265.2008.03511.
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