Senior Lecturer in Pharmacology & Education
Dr Sadani Cooray graduated from University College London with an MSc in General and Medical Microbiology in 1998 and from the University of Oxford with an MSc by Research in Genetics/Neuroscience in 2001. She obtained her BSc (Hons) in Biotechnology from South Bank University in 1997. She worked at the Medical Research Council, Harwell and the Public Health England, Colindale before joining the William Harvey Research Institute in 2003. She was awarded a PhD in Endocrinology in 2006 from QMUL under the guidance of Prof. Adrian Clark. During her PhD she played a major role in establishing the function of the MRAP (Melanocortin Receptor Accessory) Protein, which is encoded by a novel gene that was mutated in patients with Familial Glucocorticoid Deficiency type 2.
In 2006, Dr Cooray was awarded the Outstanding Young Investigator award from the WHRI and was also the recipient of the Wellcome Trust VIP award. She started her MRC funded postdoctoral fellowship with Prof. Clark in 2007 to further the work carried out on the ACTH receptor and MRAP. During this time she also demonstrated the influence of the E3 Ubiquitin ligase Mahogunin on the ACTH receptor thus revealing a new level of regulation of this receptor complex. She was awarded the Outstanding Young Investigator awards at the European Congress for Endocrinology (by Novartis) in Budapest in 2007 and at ENDO in San Diego in 2010.
She joined the Centre for Biochemical Pharmacology in 2011 as a Wellcome Trust funded Senior postdoctoral research fellow investigating the anti and proinflammatory properties of the Formyl peptide receptors under the mentorship of Prof. Mauro Perretti and Prof. Rod Flower.
In 2013 she was awarded a lectureship (HEFCE) in Pharmacology and Education. She was appointed the Programme Lead for the new BSc degree in Pharmacology & Innovative Therapeutics (WHRI), which will commence in 2015, and the BSc Biomedical Sciences/Pharmacology degree (SBCS &SMD) having designed the entire pharmacology curriculum for both. She is also a module Lead for both degrees, a tutor for SSC2 students and a mentor for BMedSci and GEP students. She has supervised BMedSci students and lectured MBBS and PhD students.
Summary of Research
Dr Cooray’s Research interests lie in the area of G protein coupled receptors in the context of endocrine function and Inflammation.
Ligand induced Conformational Change of the ALX receptor
The human Formyl Peptide Receptor family (FPR1, FPR2/ALX and FPR3) belongs to the superfamily of class A GPCRs and is responsive to a variety of agonists. FPR2 also called ALX (the lipoxin A4 receptor), conveys the proresolving properties of lipoxin A4 and annexin A1 (AnxA1) and the proinflammatory signals elicited by serum amyloid protein A and cathelicidins, among others. Coimmunoprecipitation and bioluminescence resonance energy transfer assays (BRET) revealed constitutive dimerization of the receptors; significantly, AnxA1, but not serum amyloid protein A, could activate ALX homodimers. A p38/MAPK-activated protein kinase/heat shock protein 27 signaling signature was unveiled after AnxA1 application, leading to generation of IL-10, as measured in vitro (in primary monocytes) and in vivo (after i.p. injection in the mouse). The latter response was absent in mice lacking the ALX ortholog. Using a similar approach, ALX/FPR1 heterodimerization evoked using the panagonist peptide Ac2-26, identified a JNK-mediated proapoptotic path that was confirmed in primary neutrophils. These findings provided a molecular mechanism that accounts for the dual nature of ALX and indicated that agonist binding and dimerization state contribute to the conformational landscape of FPRs.
(Figure taken from a commentary written for: Cooray SN, Clark A.J, Flower R.J & Perretti M, 2013, Ligand specific activation of ALX/FPR2: Identification of conformational changes associated with pro-resolving functional responses, Proc Natl Acad Sci, 110(45): 18232-7) by Filep et al, 2013, Biasing the lipoxin A4/formyl peptide receptor 2 pushes inflammatory resolution, Proc Natl Acad Sci , 5;110(45):18033-4.
For a full list of publist publications click here
Cooray SN, Gobbetti T, Montero-Melendez T, McArthur S, Thompson D, Clark AJ, Flower RJ, Perretti M (2013) Ligand specific activation of ALX/FPR2: Identification of conformational changes associated with pro-resolving functional responses, Proc Natl Acad Sci, 110(45): 18232-7)
Cooray SN, Guasti L, Clark AJ (2011) The E3 ubiquitin ligase Mahogunin ubiquitinates the melanocortin 2 receptor, Endocrinology 152(11):4224-31
Cooray SN, Chung TT, Mazhar K, Szidonya L., Clark A.J, (2011) Bioluminescence Resonance Energy Transfer reveals the adrenocorticotropin (ACTH) induced conformational change of the activated ACTH receptor complex in living cells, Endocrinology 152(2):495-502.
Cooray SN, Clark AJ, (2011) Melanocortin receptors and their accessory proteins, Mol Cell Endocrinol 15; 331(2):215-21
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 14;106(15):6146-51
Cooray SN, Chan L, Webb TR, Metherell L, Clark AJ, (2009), Accessory proteins are vital for the functional expression of certain G protein-coupled receptors, Mol Cell Endocrinol, 5;300(1-2):17-24
Webb TR, Chan L, Cooray SN, Cheetham ME, Chapple JP, Clark AJ, (2009), Distinct melanocortin 2 receptor accessory protein domains are required for melanocortin 2 receptor interaction and promotion of receptor trafficking, Endocrinology, 150(2):720-6
Cooray SN, Almiro Do Vale I, leung KY, Webb TR, Chapple JP, Egertova M, Cheetham ME, Elphick MR, Clark AJ, (2008), The melanocortin 2 receptor accessory protein exists as a homodimer and is essential for the function of the melanocortin 2 receptor in the mouse y1 cell line, Endocrinology, 149(4):1935-41
Chung TT, Webb TR, Chan LF, Cooray SN, Metherell LA, King PJ, Chapple JP, Clark AJ, (2008), The majority of adrenocorticotropin receptor (melanocortin 2 receptor) mutations found in familial glucocorticoid deficiency type 1 lead to defective trafficking of the receptor to the cell surface, J Clin Endocrinol Metab, 93(12): 4948-54
Metherell LA, Chapple JP, Cooray S, David A, Becker C, Rüschendorf F, Naville D, Begeot M, Khoo B, Nürnberg P, Huebner A, Cheetham ME & Clark AJL. (2005) Mutations in MRAP, encoding a novel interacting partner of the ACTH receptor, cause Familial Glucocorticoid Deficiency Type 2. Nature Genetics 37: 166 -170.