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Molecular Medicine


Roy Smith, Ph.D.

Professor Emeritus
Department of Molecular Medicine
Florida Campus
Laboratory Website

Research Focus

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

Awards & Professional Activities

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

Editorial Boards

2002 – Present: Steroids

2004 – Present: Human Molecular Genetics

2003 – Present: Neuro-Endocrinology

2005 – Present: Honorary Editorial Board, Clinical Interventions in Aging

2006 – Present: International Journal of Medical Science

Selected References

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


Department of Metabolism & Aging

Molecular Medicine Seminar Series
Center for Physiological Proteomics
Department Contacts

CA Faculty

Asahara, Hiroshi
Balch, William E.
Boddy, Michael
Buxbaum, Joel
Catz, Sergio
Conti, Bruno
Cravatt, Benjamin
D'Lima, Darryl
DerMardirossian, Celine
Deryugina, Elena
Elias, Darlene
Encalada, Sandra
Felding, Brunhilde
Fowler, Velia
Friedlander, Martin
Gerace, Larry
Gottesfeld, Joel
Griffin, John
Hanneken, Anne
Heeb, Mary Jo
Henderson, Scott
Hoch, James
Johnson, Eric
Kanaji, Taisuke
Koziol, James
Lamia, Katja
Lazzerini Denchi, Eros
Lipton, Stuart
Loring, Jeanne F.
Loskutoff, David
Lotz, Martin
Makarenkova, Helen P.
Mc Millan, Robert
Miles, Lindsey
Milner, Richard
Modena, Brian
Mosnier, Laurent
Nicholson, Laura
Paulson, James C.
Perego, Marta
Petrascheck, Michael
Pollard, Kenneth Michael
Quigley, James P.
Reed, Steven
Roberts, Edward
Rosen, Hugh
Ruggeri, Zaverio
Russell, Paul
Saez, Enrique
Smider, Vaughn
Srinivasan, Supriya
Steinhubl, Steven
Sutcliffe, J.
Tan, Eng
Topol, Eric
Vanderklish, Peter
Vogt, Peter K.
Wiseman, Luke
Wittenberg, Curt
Wolan, Dennis W.
Wu, Peng
Wu, Xiaohua
Yang, Xiang-Lei
Yates III, John

FL Faculty

Bannister, Thomas
Bohn, Laura M.
Cameron, Michael
Duckett, Derek
Gill, Matt
Griffin, Patrick
Hansen, Scott
Joazeiro, Claudio
Kamenecka, Theodore
Kissil, Joseph
Luo, Junli
McDonald, Patricia
Miller, Courtney
Niedernhofer, Laura
Phinney, Donald G.
Robbins, Paul
Scampavia, Louis
Schimmel, Paul
Smith, Roy
Spicer, Timothy

Affiliated Faculty

Cline, Hollis
Kojetin, Douglas
Lairson, Luke
Paegel, Brian
Rumbaugh, Gavin
Shen, Ben
Solt, Laura A
Su, Andrew
Wu, Chunlei
Ye, Li

Adjunct Faculty