The Scripps Research Institute's Department of Metabolism and Aging at the Scripps Florida campus is focused on understanding the basis of metabolic diseases and identifying the physiological changes that cause loss of function during aging. By understanding the processes associated with these diseases, scientists can take advantage of the unique facilities offered at Scripps Florida that include medicinal chemistry and pharmacology; both are essential for the efficient development of safe and novel therapies.
Multidisciplinary approaches create synergy in the discovery process. Areas of research include developmental biology of fat and muscle, cartilage catabolism, whole body metabolism, molecular genetics, bioinformatics, imaging, and structural studies on G-protein coupled receptors (GPCRs). The department also applies zebra fish and mouse genetics to help identify safe drug targets for treatment and prevention of functional deficiencies. Such approaches led to identification of a new GPCR, GHS-R1a, and its endogenous agonist, a hormone called ghrelin. A decline in ghrelin production appears to explain many of the changes occurring during normal aging.
In animal models, ghrelin administration inhibits neuronal loss associated with Parkinson's disease, and stroke. Ghrelin also regulates metabolic pathways and the immune system. Identifying the key structural elements of the GHS-R1a is being done in collaboration with Scripps La Jolla. Ongoing studies are designed to elucidate the mechanisms involved.
Ph.D., Organic Chemistry, University of London, 1967
1968: Elected Associate Royal Institute of Chemistry
1969 – 1970: Chairman, Chemical Society of Queen Mary College, London University
1975: Elected Chartered Chemist of U.K.
1988 – 1989: Vice President & President Elect, Society of Basic Urologic Research (AUA)
1989 – 1990: President, Society of Basic Urologic Research (AUA)
1992: Merck & Co. Management Award
1996: University of District of Columbia Beta Kappa Chi Scientific Honor Society Award for encouraging women and minorities in the sciences
2003 – Present: National Scientific Advisory Council, American Federation for Aging Research
2003 – 2006: Endocrine Society, Program Committee
2002 – Present: Steroidsâ€¨
2004 – Present: Human Molecular Geneticsâ€¨
2003 – Present: Neuro-Endocrinologyâ€¨
2005 – Present: Honorary Editorial Board, Clinical Interventions in Agingâ€¨
2006 – Present: International Journal of Medical Science
Cowley, M., Smith, R.G., Diano, S., Tschop, M., Pronchuk, N., Grove, K., Strasburger, C., Bidlingmaier, M., Esterman, M., Heiman, M., Garcia-Segura, L., Nillni, E., Mendez, P., Low, M., Sotonyi, P., Friedman, J., Liu, H., Pinto, S., Colmers, WS., Cone, R., Horvath, T. (2003) The distribution and mechanism of action of ghrelin in the CNS demonstrates a novel hypothalamic circuit regulating energy homeostasis. Neuron 37(4)649-661.
Sun, Y., Wang, P., Zheng, H., Smith, R.G. (2004) Ghrelin stimulation of growth hormone release and appetite is mediated through the growth hormone secretagogue receptor. Proc. Natl. Acad. Sciences, USA 101:4679-4684.
Smith, R.G. (2005). Development of growth hormone secretagogues. Endocrine Reviews 26(3):346-360.
Jiang, H., Betancourt, L., Smith, R.G. (2006) Ghrelin amplifies dopamine signaling by crosstalk involving Formation of GHS-R/D1R Heterodimers. Molecular Endocrinology 20:1772-1785.
Sun, Y., Asnicar, M., Saha, P.K., Chan, L., Smith, R.G. (2006) Ablation of ghrelin gene improves the diabetic but not obese phenotype of ob/ob mice. Cell Metabolism 3:379-386.
Wang G-L, Shi X, Salisbury E, Sun Y, Albrecht JH, Smith RG and Timchenko NA. (2006) Cyclin D3 maintains growth inhibitory activity of C/EBPα by stabiliziang C/EBPα-cdk2 and C/EBPα-Brm complexes. Molecular and Cellular Biology 26: 2570-2582.
Wang G-L, Shi X, Salisbury E, Sun Y, Albrecht JH, Smith RG and Timchenko NA. (2007) Growth Hormone Corrects Proliferation and Transcription of Phosphoenolpyruvate Carboxykinase in Livers of Old Mice via Elimination of CCAAT/Enhancer-binding Protein-Brm Complex. J. Biol. Chem. 282:1468 – 1478
Dixit V. D., Yang H, Sun Y, Weeraratna AT, Youm Y-H, Smith R. G. and Taub DD. (2007) Ghrelin promotes thymopoiesis during aging. Journal of Clinical Investigation 117:2778-2790.
Sun Y, Asnicar M, Smith R. G. (2007) Central and Peripheral Roles of Ghrelin on Glucose Homeostasis. Neuroendocrinology 86(3):215-228.
Garcia J. M, Cata J. P., Dougherty P. M., and Smith R. G. (2008) Ghrelin prevents cisplatin-induced mechanical hyperalgesia and cachexia. Endocrinology 149(2):455-460. PMCID: PMC2219295.
Smith R.G, Sun Y, Jiang H, Albarran-Zeckler R, and Timchenko N (2007) Ghrelin receptor agonists show potential as interventive gents during aging. Ann N Y Acad Sci 1119:147-164.
Yang H, Dixit V. D., Patel K, Vandanmagsar B., Collins G., Sun Y., Smith R. G., and Taub D.D. (2008) Reduction in hypophyseal growth hormone and prolactin expression due to deficiency in ghrelin receptor signaling is associated with Pit-1 suppression: Relevance to the immune system. Brain Behav Immun. (2008) 22:1138-1145. PMCID: PMC2783985.
Hill J. T., Mastracci T. L., Vinton C., Doyle M. L. Anderson K. R,, Loomis Z. L,, Schrunk J. M., Minic A. D., Pugliese A., Sun Y., Smith R. G., and Sussel L. (2009) Ghrelin is dispensable for embryonic pancreatic islet development and differentiation. Regulatory Peptides 157:51-56 PMID: 19268691.
Szentirmai, E., Kapas, L., Sun, Y., Smith, R.G., and Krueger, J.M. (2009) The preproghrelin gene is required for the normal integration of thermoregulation and sleep in mice. Proc Natl Acad Sci USA 106(33):14069-74. PMCID: PMC272902.
Smith, RG (2009) From GH to Billy Ghrelin (Preview). Cell Metab 10(2):82-83.
Szentirmai, E., Kapás, Sun, Y., Smith, RG, Krueger, JM (2010) Restricted feeding-induced sleep, activity, and body temperature changes in normal and preproghrelin-deficient mice. Am J Physiol Regul Integr Comp Physiol 298 R467-R477. PMCID: PMC2828180