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Marginal phenotypes with orphan GPCRs: a GPR37L1 case study
- Dr. Nicola Smith -
- UNSW Sydney -
- Kensington, Australia -
Abstract
In the absence of identified ligands, transgenic mice lacking an orphan GPCR of interest are often the only way to discern the potential physiological or pathophysiological impact of a particular receptor. For the brain-specific orphan GPR37L1, the first reported knockout mouse displayed a marked elevation in blood pressure and concomitant cardiac hypertrophy, suggesting it could be a master regulator of blood pressure homeostasis. More recent studies, however, have reported roles in neuroprotection and neurodevelopment, while our own studies have found the cardiovascular and an associated cardiometabolic phenotype of GPR37L1 knockout mice to be far more subtle. In this presentation, I will describe our efforts to understand the contribution of GPR37L1 to cardiovascular homeostasis and highlight some of the challenges we faced without available pharmacological tools.
About Dr. Nicola Smith
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 Ph.D. 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 (the 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 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).
Author list and affiliations
- Nicola J Smith, UNSW Sydney
Dr. Nicola Smith on the web
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