Dr Nicola Smith

Fields of research: Receptors and Membrane Biology, Basic Pharmacology, Cardiology (incl. Cardiovascular Diseases)

Contact Details

Phone: +61 2 (0) 9385 1472
Email: nicola.smith@unsw.edu.au

Tabs

Main

Dr Nicola J. Smith is passionate about all things G protein-coupled receptor – the largest family of membrane proteins in the human genome.

Nicola completed her undergraduate training in pharmacology and biochemistry at the University of Melbourne in 2002 (first class Honours) before commencing a PhD at the Baker Heart Research Institute under the tutelage of Profs Walter Thomas and Ross Hannan, where she studied the role of EGFR transactivation by the angiotensin II receptor in left ventricular hypertrophy (Uni Melb, 2003-7). In 2006, Nicola was awarded a joint NHMRC/NHF CJ Martin Overseas Fellowship to work in the laboratory of Prof Graeme Milligan, a world expert on G protein-coupled receptors (University of Glasgow, 2007-2011). In early 2011, Nicola returned to the Victor Chang Cardiac Research Institute to join the laboratory of Prof Robert Graham, a leader in the role of G protein-coupled receptors in cardiac physiology and pathophysiology, where she established a research program based upon orphan, or un-liganded, receptors (2011-2015). Nicola was appointed Group Leader in 2016 and was awarded a National Heart Foundation Future Leader Fellowship the following year. She recently accepted a senior lecturer appointment at UNSW Sydney School of Medical Sciences where she heads up the Orphan Receptor Laboratory, as well as teaching into several pharmacology courses. In addition to her pharmacological studies, Nicola is a passionate science communicator and has worked as a radio science presenter, acted as Ambassador for IMB’s ‘When I Grow Up’ campaign and has spoken to many school and community groups about the joys of science and discovery.

Nicola currently serves on the Board of Directors of the Australasian Society for Experimental Pharmacologists and Toxicologists (ASCEPT).

For current projects, please contact Nicola for more information.

University role:

National Heart Foundation Future Leader Fellow and Laboratory Head, Orphan Receptor Laboratory

Grants:

National Heart Foundation Future Leader Fellowship (Level 2) “Understanding orphan G protein-coupled receptors in cardiovascular health and disease” (2017-2021)
NHMRC Project Grant 1120483 (CIC) “Role of RNA-binding proteins in cardiomyocyte physiology” (2017-2020)
St Vincent’s Clinic Foundation Froulop Research Grant (CIA) “Investigating the interplay between the sympathetic nervous system, anxiety and gender on blood pressure homeostasis” (2018)
Australian Government (CIA) Global Connections Fund Seed Grant (2017)
St Vincent’s Clinic Foundation Annual Grant 6 (CIA) “A new cardioprotective factor in left ventricular hypertrophy?” (2016)
Mostyn Family Foundation Ongoing Bequest (CIA) “To fund drug discovery addressing the underlying causes of hypertension”
NHMRC Project Grant 1061804 (CIB) “Does GPR84 mediate the beneficial effects of medium chain fatty acids?” (2014-2016)
NHMRC/NHF CJ Martin Fellowship (459413) “Molecular determinants of GPR40 signalling and regulation in disease” (2007-2013)
UNSW Research Infrastructure Scheme 2016 Grant #RG 163080, Housley, Bryce, Finch, Jones, Liu, Moorhouse, Ong, Power, SMITH, Turner, Vandenberg “Faculty infrastructure project: benchtop system integrating multi-mode microplate optics with precision, programmable liquid handling”.

Awards:

2015 Garvan Institute Oral Prize
2014 St Vincent’s Precinct Rising Star
2012 Paul Korner Seminar Speaker Award, Victor Chang Cardiac Research Institute
2012 37th Lorne Conference on Protein Structure and Function Young Investigator Award
2011 Young Tall Poppy Award, NSW
2011 ASCEPT Denis Wade New Investigator Award
2009 ‘Paper of the Week’, Journal of Biological Chemistry
2007 Highest ranked applicant for the National Heart Foundation of Australia Overseas Fellowship (accepted joint funding with NHMRC)
2004 Winner of the Best Poster Prize, Gordon Research Conference on Angiotensin
2004 Winner, Rod Andrews Poster Prize at the Baker Heart Research Institute
2001 Awarded the Pharmacology Prize for top final year student, University of Melbourne

Keywords:

cardiovascular disease

g-protein coupled receptors

drug discovery

pharmacology

biochemistry & molecular biology

orphans

Research

Socio-economic Objective (SEO) tags:

Expanding Knowledge

Cardiovascular System and Diseases

Teaching & Supervision

I am available to supervise:

Yes

Areas of supervision:

Molecular pharmacology of G protein-coupled receptors.

Currently supervising:

Ms Margaret (Meg) Mouat, PhD student
Mr Sean Souchiart So, PhD student
Mr Brendan Wilkins, PhD student
Ms Kinjal Patel, PhD student
Mr Justin Moon, Hons student
Ms Annie Chen, co-supervised Hons student
Ms Jennifer Grant, co-supervised Hons student

Lab alumni:
James Coleman, post-doc, PhD and Hons
Tony Ngo, PhD
Amy Nicks, PhD (Uni Leeds)
Brendan Wilkins, Research Assistant
Peter Keov, post-doc
Margaret (Meg) Mouat, Hons
Eric Cheung, Hons
Rhyll Smythe, Hons
Andrew Cleave, Hons
Theodore Nettleton, Hons

Supervision keywords:

g-protein-coupled receptors

pharmacology

membrane proteins

cardiovascular disease

biochemistry & molecular biology

Teaching:

I am a Senior Lecturer and teach in various pharmacology courses, including Molecular Pharmacology (PHAR3102) and Drug Design, Discovery and Development (PHAR3101).

Media

LinkedIn:

https://www.linkedin.com/in/nicola-j-smith-b54b0231/

Twitter Account:

https://twitter.com/smith_orphans?lang=en

Publications related to this Person

Book Chapters

So SS; Ngo T; Keov P; Smith NJ; Kufareva I, 2019, 'Tackling the complexities of orphan GPCR ligand discovery with rationally assisted approaches', in Jastrzebska B; Park PSH (ed.), GPCRs: Structure, Function, and Drug Discovery, ACADEMIC PRESS LTD-ELSEVIER SCIENCE LTD, pp. 295 - 334, http://dx.doi.org/10.1016/B978-0-12-816228-6.00016-7

Journal articles

Ng CA; Perry MD; Liang W; Smith NJ; Foo B; Shrier A; Lukacs GL; Hill AP; Vandenberg JI, 2020, 'High-throughput phenotyping of heteromeric human ether-à-go-go-related gene potassium channel variants can discriminate pathogenic from rare benign variants', Heart Rhythm, vol. 17, pp. 492 - 500, http://dx.doi.org/10.1016/j.hrthm.2019.09.020

Coleman JLJ; Ngo T; Schmidt J; Mrad N; Liew CK; Jones NM; Graham RM; Smith NJ, 2019, 'Retraction: Metalloprotease cleavage of the N terminus of the orphan G protein-coupled receptor GPR37L1 reduces its constitutive activity (Science Signaling (2016) 9 (ra36) DOI: 10.1126/scisignal.aad1089)', Science Signaling, vol. 12, http://dx.doi.org/10.1126/scisignal.aba2063

Montgomery MK; Osborne B; Brandon AE; O'Reilly L; Fiveash CE; Brown SHJ; Wilkins BP; Samsudeen A; Yu J; Devanapalli B; Hertzog A; Tolun AA; Kavanagh T; Cooper AA; Mitchell TW; Biden TJ; Smith NJ; Cooney GJ; Turner N, 2019, 'Regulation of mitochondrial metabolism in murine skeletal muscle by the medium-chain fatty acid receptor Gpr84', FASEB Journal, vol. 33, pp. 12264 - 12276, http://dx.doi.org/10.1096/fj.201900234R

Sobti M; Ishmukhametov R; Bouwer JC; Ayer A; Suarna C; Smith NJ; Christie M; Stocker R; Duncan TM; Stewart AG, 2019, 'Cryo-EM reveals distinct conformations of E. coli ATP synthase on exposure to ATP', eLife, vol. 8, http://dx.doi.org/10.7554/eLife.43864

Mouat MA; Coleman JLJ; Smith NJ, 2018, 'GPCRs in context: sexual dimorphism in the cardiovascular system', British Journal of Pharmacology, vol. 175, pp. 4047 - 4059, http://dx.doi.org/10.1111/bph.14160

Coleman JLJ; Mouat MA; Wu J; Jancovski N; Bassi JK; Chan AY; Humphreys DT; Mrad N; Yu ZY; Ngo T; Iismaa S; Dos Remedios CG; Feneley MP; Allen AM; Graham RM; Smith NJ, 2018, 'Orphan receptor GPR37L1 contributes to the sexual dimorphism of central cardiovascular control', Biology of Sex Differences, vol. 9, http://dx.doi.org/10.1186/s13293-018-0173-y

Wirasinha RC; Vijayan D; Smith NJ; Parnell GP; Swarbrick A; Brink R; King C; Stewart G; Booth DR; Batten M, 2018, 'GPR65 inhibits experimental autoimmune encephalomyelitis through CD4⁺ T cell independent mechanisms that include effects on iNKT cells', Immunology and Cell Biology, vol. 96, pp. 128 - 136, http://dx.doi.org/10.1111/imcb.1031

Coleman JLJ; Ngo T; Smith NJ, 2017, 'The G protein-coupled receptor N-terminus and receptor signalling: N-tering a new era', Cellular Signalling, vol. 33, pp. 1 - 9, http://dx.doi.org/10.1016/j.cellsig.2017.02.004

Ngo T; Ilatovskiy AV; Stewart AG; Coleman JLJ; McRobb FM; Riek RP; Graham RM; Abagyan R; Kufareva I; Smith NJ, 2017, 'Orphan receptor ligand discovery by pickpocketing pharmacological neighbors', Nature Chemical Biology, vol. 13, pp. 235 - 242, http://dx.doi.org/10.1038/nchembio.2266

Soetanto R; Hynes CJ; Patel HR; Humphreys DT; Evers M; Duan G; Parker BJ; Archer SK; Clancy JL; Graham RM; Beilharz TH; Smith NJ; Preiss T, 2016, 'Role of miRNAs and alternative mRNA 3'-end cleavage and polyadenylation of their mRNA targets in cardiomyocyte hypertrophy', Biochimica et Biophysica Acta - Gene Regulatory Mechanisms, vol. 1859, pp. 744 - 756, http://dx.doi.org/10.1016/j.bbagrm.2016.03.010

McNamara JW; Li A; Smith NJ; Lal S; Graham RM; Kooiker KB; van Dijk SJ; Remedios CGD; Harris SP; Cooke R, 2016, 'Ablation of cardiac myosin binding protein-C disrupts the super-relaxed state of myosin in murine cardiomyocytes', Journal of Molecular and Cellular Cardiology, vol. 94, pp. 65 - 71, http://dx.doi.org/10.1016/j.yjmcc.2016.03.009

Chowdhury MKH; Wu LE; Coleman JLJ; Smith NJ; Morris MJ; Shepherd PR; Smith GC, 2016, 'Niclosamide blocks glucagon phosphorylation of Ser⁵⁵² on β-catenin in primary rat hepatocytes via PKA signalling', Biochemical Journal, vol. 473, pp. 1247 - 1255, http://dx.doi.org/10.1042/BCJ20160121

Coleman JLJ; Ngo T; Schmidt J; Mrad N; Liew CK; Jones NM; Graham RM; Smith NJ, 2016, 'Metalloprotease cleavage of the N terminus of the orphan G protein-coupled receptor GPR37L1 reduces its constitutive activity', Science Signaling, vol. 9, http://dx.doi.org/10.1126/scisignal.aad1089

Grundmann M; Tikhonova IG; Hudson BD; Smith NJ; Mohr K; Ulven T; Milligan G; Kenakin T; Kostenis E, 2016, 'A Molecular Mechanism for Sequential Activation of a G Protein-Coupled Receptor', Cell Chemical Biology, vol. 23, pp. 392 - 403, http://dx.doi.org/10.1016/j.chembiol.2016.02.014

Ngo T; Kufareva I; Coleman JLJ; Graham RM; Abagyan R; Smith NJ, 2016, 'Identifying ligands at orphan GPCRs: current status using structure-based approaches', British Journal of Pharmacology, vol. 173, pp. 2934 - 2951, http://dx.doi.org/10.1111/bph.13452

Foster SR; Porrello ER; Stefani M; Smith NJ; Molenaar P; Dos Remedios CG; Thomas WG; Ramialison M, 2015, 'Cardiac gene expression data and in silico analysis provide novel insights into human and mouse taste receptor gene regulation', Naunyn-Schmiedeberg's Archives of Pharmacology, vol. 388, pp. 1009 - 1027, http://dx.doi.org/10.1007/s00210-015-1118-1

Coleman JLJ; Brennan K; Ngo T; Balaji P; Graham RM; Smith NJ, 2015, 'Rapid knockout and reporter mouse line generation and breeding colony establishment using EUCOMM conditional-ready embryonic stem cells: A case study', Frontiers in Endocrinology, vol. 6, http://dx.doi.org/10.3389/fendo.2015.00105

Smith NJ, 2015, 'Drug discovery opportunities at the endothelin B receptor-related orphan g protein-coupled receptors, GPR37 and GPR37L1', Frontiers in Pharmacology, vol. 6, http://dx.doi.org/10.3389/fphar.2015.00275

Ngo T; Coleman JLJ; Smith NJ, 2015, 'Using constitutive activity to defi ne appropriate high-throughput screening assays for orphan G protein-coupled receptors', Methods in Molecular Biology, vol. 1272, pp. 91 - 106, http://dx.doi.org/10.1007/978-1-4939-2336-6_7

Yu ZY; Tan JC; McMahon AC; Iismaa SE; Xiao H; Kesteven SH; Reichelt ME; Mohl MC; Smith NJ; Fatkin D; Allen D; Head SI; Graham RM; Feneley MP, 2014, 'RhoA/ROCK signaling and pleiotropic α1A-adrenergic receptor regulation of cardiac contractility', PLoS ONE, vol. 9, http://dx.doi.org/10.1371/journal.pone.0099024

Smith NJ, 2012, 'Low affinity GPCRs for metabolic intermediates: Challenges for pharmacologists', Frontiers in Endocrinology, vol. 3, http://dx.doi.org/10.3389/fendo.2012.00001

Smith NJ; Ward RJ; Stoddart LA; Hudson BD; Kostenis E; Ulven T; Morris JC; Tränkle C; Tikhonova IG; Adams DR; Milligan G, 2011, 'Extracellular loop 2 of the free fatty acid receptor 2 mediates allosterism of a phenylacetamide ago-allosteric modulator', Molecular Pharmacology, vol. 80, pp. 163 - 173, http://dx.doi.org/10.1124/mol.110.070789

Smith NJ; Chan HW; Qian H; Bourne AM; Hannan KM; Warner FJ; Ritchie RH; Pearson RB; Hannan RD; Thomas WG, 2011, 'Determination of the exact molecular requirements for type 1 angiotensin receptor epidermal growth factor receptor transactivation and cardiomyocyte hypertrophy', Hypertension, vol. 57, pp. 973 - 980, http://dx.doi.org/10.1161/HYPERTENSIONAHA.110.166710

Schmidt J; Smith NJ; Christiansen E; Tikhonova IG; Grundmann M; Hudson BD; Ward RJ; Drewke C; Milligan G; Kostenis E; Ulven T, 2011, 'Selective orthosteric free fatty acid receptor 2 (FFA2) agonists: Identification of the structural and chemical requirements for selective activation of FFA2 versus FFA3', Journal of Biological Chemistry, vol. 286, pp. 10628 - 10640, http://dx.doi.org/10.1074/jbc.M110.210872

Flores-Muñoz M; Smith NJ; Haggerty C; Milligan G; Nicklin SA, 2011, 'Angiotensin1-9 antagonises pro-hypertrophic signalling in cardiomyocytes via the angiotensin type 2 receptor', Journal of Physiology, vol. 589, pp. 939 - 951, http://dx.doi.org/10.1113/jphysiol.2010.203075

Smith NJ; Bennett KA; Milligan G, 2011, 'When simple agonism is not enough: Emerging modalities of GPCR ligands', Molecular and Cellular Endocrinology, vol. 331, pp. 241 - 247, http://dx.doi.org/10.1016/j.mce.2010.07.009

Hudson BD; Smith NJ; Milligan G, 2011, 'Experimental Challenges to Targeting Poorly Characterized GPCRs. Uncovering the Therapeutic Potential for Free Fatty Acid Receptors', Advances in Pharmacology, vol. 62, pp. 175 - 218, http://dx.doi.org/10.1016/B978-0-12-385952-5.00006-3

Jenkins L; Brea J; Smith NJ; Hudson BD; Reilly G; Bryant NJ; Castro M; Loza MI; Milligan G, 2010, 'Identification of novel species-selective agonists of the G-protein-coupled receptor GPR35 that promote recruitment of β-arrestin-2 and activate Gα13', Biochemical Journal, vol. 432, pp. 451 - 459, http://dx.doi.org/10.1042/BJ20101287

Smith NJ; Milligan G, 2010, 'Allostery at G protein-coupled receptor homo- and heteromers: Uncharted pharmacological landscapes', Pharmacological Reviews, vol. 62, pp. 701 - 725, http://dx.doi.org/10.1124/pr.110.002667

Schröder R; Janssen N; Schmidt J; Kebig A; Merten N; Hennen S; Müller A; Blättermann S; Mohr-Andrä M; Zahn S; Wenzel J; Smith NJ; Gomeza J; Drewke C; Milligan G; Mohr K; Kostenis E, 2010, 'Deconvolution of complex G protein-coupled receptor signaling in live cells using dynamic mass redistribution measurements', Nature Biotechnology, vol. 28, pp. 943 - 949, http://dx.doi.org/10.1038/nbt.1671

Milligan G; Stoddart LA; Smith NJ, 2009, 'Agonism and allosterism: The pharmacology of the free fatty acid receptors FFA2 and FFA3', British Journal of Pharmacology, vol. 158, pp. 146 - 153, http://dx.doi.org/10.1111/j.1476-5381.2009.00421.x

Smith NJ; Stoddart LA; Devine NM; Jenkins L; Milligan G, 2009, 'The action and mode of binding of thiazolidinedione ligands at free fatty acid receptor 1', Journal of Biological Chemistry, vol. 284, pp. 17527 - 17539, http://dx.doi.org/10.1074/jbc.M109.012849

Stoddart LA; Smith NJ; Milligan G, 2008, 'International union of pharmacology. LXXI. Free fatty acid receptors FFA1, -2, and -3: Pharmacology and pathophysiological functions', Pharmacological Reviews, vol. 60, pp. 405 - 417, http://dx.doi.org/10.1124/pr.108.00802

Stoddart LA; Smith NJ; Jenkins L; Brown AJ; Milligan G, 2008, 'Conserved polar residues in transmembrane domains V, VI, and VII of free fatty acid receptor 2 and free fatty acid receptor 3 are required for the binding and function of short chain fatty acids', Journal of Biological Chemistry, vol. 283, pp. 32913 - 32924, http://dx.doi.org/10.1074/jbc.M805601200

Milligan G; Smith NJ, 2007, 'Allosteric modulation of heterodimeric G-protein-coupled receptors', Trends in Pharmacological Sciences, vol. 28, pp. 615 - 620, http://dx.doi.org/10.1016/j.tips.2007.11.001

Smith NJ; Luttrell LM, 2006, 'Signal switching, crosstalk, and arrestin scaffolds: Novel G protein-coupled receptor signaling in cardiovascular disease', Hypertension, vol. 48, pp. 173 - 179, http://dx.doi.org/10.1161/01.HYP.0000232641.84521.92

Chan HW; Smith NJ; Hannan RD; Thomas WG, 2006, 'Tackling the EGFR in pathological tissue remodelling', Pulmonary Pharmacology and Therapeutics, vol. 19, pp. 74 - 78, http://dx.doi.org/10.1016/j.pupt.2005.04.005

Thomas WG; Qian H; Smith NJ, 2004, 'When 6 is 9: 'Uncoupled' AT1 receptors turn signalling on its head', Cellular and Molecular Life Sciences, vol. 61, pp. 2687 - 2694, http://dx.doi.org/10.1007/s00018-004-4245-2

Smith NJ; Chan HW; Osborne JE; Thomas WG; Hannan RD, 2004, 'Hijacking epidermal growth factor receptors by angiotensin II: New possibilities for understanding and treating cardiac hypertrophy', Cellular and Molecular Life Sciences, vol. 61, pp. 2695 - 2703, http://dx.doi.org/10.1007/s00018-004-4244-3

Devlin MG; Smith NJ; Ryan OM; Guida E; Sexton PM; Christopoulos A, 2004, 'Regulation of serotonin 5-HT 2C receptors by chronic ligand exposure', European Journal of Pharmacology, vol. 498, pp. 59 - 69, http://dx.doi.org/10.1016/j.ejphar.2004.07.102

Smith NJ; Hannan RD; Thomas WG; Lew RA, 2003, 'AngiotensinII mediates cardiomyocyte hypertrophic growth pathways via MMP-dependent HB-EGF liberation', Letters in Peptide Science, vol. 10, pp. 431 - 435, http://dx.doi.org/10.1007/BF02442574

Ngo T; Wilkins BP; So SS; Keov P; Chahal KK; Finch AM; Coleman JLJ; Kufareva I; Smith NJ, 'Orphan G protein-coupled receptor, GPR37L1: pharmacological toolbox empty once again', , http://dx.doi.org/10.1101/2020.09.11.290486

Conference Papers

Conference Abstracts

Montgomery MK; Brandon AE; O'Reilly L; Osborne B; Fiveash CE; Brown SH; Smith NJ; Mitchell TW; Biden TJ; Cooney GJ; Turner N, 2016, 'The free fatty acid receptor GPR84: A new player in glucose tolerance and mitochondrial function?', in DIABETOLOGIA, SPRINGER, Munich, GERMANY, Vol. 59, pp. S322 - S322, presented at 52nd Annual Meeting of the European-Association-for-the-Study-of-Diabetes (EASD), Munich, GERMANY, 12 September 2016 - 16 September 2016, http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000398373702048&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=891bb5ab6ba270e68a29b250adbe88d1

Foster SR; Porrello ER; Stefani M; Smith NJ; Molenaar P; dos Remedios CG; Thomas WG; Ramialison M, 2014, 'Transcriptional Regulation of Taste Receptor Genes: Novel Insights From In Silico and Cardiac Gene Expression Analyses', in CHEMICAL SENSES, OXFORD UNIV PRESS, Brisbane, AUSTRALIA, Vol. 40, pp. 366 - 367, presented at 15th Scientific Meeting of the Australasian-Association-for-ChemoSensory-Science (AACSS), Brisbane, AUSTRALIA, 03 December 2014 - 05 December 2014, http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000357868900036&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=891bb5ab6ba270e68a29b250adbe88d1

Nicks AM; Li M; Wu J; Kesteven SH; Fenely MP; Smith NJ; Iismaa SE; Graham RM, 2014, 'A SURGICAL MODEL OF HYPERTENSION AND LEFT VENTRICULAR HYPERTROPHY IN MICE BY SUPRARENAL AORTIC CONSTRICTION', in HYPERTENSION, LIPPINCOTT WILLIAMS & WILKINS, Adelaide, AUSTRALIA, Vol. 65, pp. E39 - E39, presented at 36th Annual Scientific Meeting of the High-Blood-Pressure-Research-Council-of-Australia (HBPRCA), Adelaide, AUSTRALIA, 26 November 2014 - 28 November 2014, http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000352490400055&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=891bb5ab6ba270e68a29b250adbe88d1

Molecular Pharmacology Drug Design