Roger D. Cone, Ph.D.

Professor

roger.cone@vanderbilt.edu

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Faculty Appointments
Chair of the Department of Molecular Physiology and Biophysics Professor of Molecular Physiology and Biophysics Joe C. Davis Chair in Biomedical Science
Education
Ph.D., Biology, Massachusetts Institute of Technology, Cambridge, MassachusettsB.A., Biochemistry, Princeton University, Princeton, New Jersey
Office Address
702 Light Hall
2215 Garland Avenue
Nashville, TN 37232-0615
Research Description
Our primary interest is understanding how the central nervous system regulates energy stores. We are focused not only on the normal process, but also on the pathophysiological mechanisms that lead to common obesity, severe monogenic obesity, metabolic syndrome, cachexia or disease wasting, anorexia nervosa, and other eating disorders. A theme of the lab has been understanding the role of the central melanocortin system in these processes.

Because we are focused on a complex biological problem that impacts multiple physiological systems, we apply a wide variety of techniques including genetics, molecular biology, neuroantomy, and electrophysiology. Our work also spans a wide range of organisms, from zebrafish to mouse, to humans. New projects include development of the zebrafish as a model system for whole genome forward genetics of energy homeostasis, and identification of genes predisposing humans to anorexia nervosa.
Research Keywords
Regulation of Energy Homeostasis by the Central Nervous System; Biology of Melanocortin Peptides and Receptors
Publications
Renquist BJ, Murphy JG, Larson EA, Olsen D, Klein RF, Ellacott KL, Cone RD. Melanocortin-3 receptor regulates the normal fasting response. Proc. Natl. Acad. Sci. U.S.A [print-electronic]. 2012 Jun 6/5/2012; 109(23): E1489-98. PMID: 22573815, PMCID: PMC3384161, PII: 1201994109, DOI: 10.1073/pnas.1201994109, ISSN: 1091-6490.

Hatoum IJ, Stylopoulos N, Vanhoose AM, Boyd KL, Yin DP, Ellacott KL, Ma LL, Blaszczyk K, Keogh JM, Cone RD, Farooqi IS, Kaplan LM. Melanocortin-4 receptor signaling is required for weight loss after gastric bypass surgery. J. Clin. Endocrinol. Metab [print-electronic]. 2012 Jun; 97(6): E1023-31. PMID: 22492873, PMCID: PMC3387412, PII: jc.2011-3432, DOI: 10.1210/jc.2011-3432, ISSN: 1945-7197.

Zhang C, Forlano PM, Cone RD. AgRP and POMC neurons are hypophysiotropic and coordinately regulate multiple endocrine axes in a larval teleost. Cell Metab [print-electronic]. 2012 Feb 2/8/2012; 15(2): 256-64. PMID: 22245570, PMCID: PMC3332529, PII: S1550-4131(11)00497-9, DOI: 10.1016/j.cmet.2011.12.014, ISSN: 1932-7420.

Cone RD, Simerly RB. Leptin grows up and gets a neural network. Neuron. 2011 Jul 7/14/2011; 71(1): 4-6. PMID: 21745633, PMCID: PMC3175484, PII: S0896-6273(11)00563-0, DOI: 10.1016/j.neuron.2011.06.033, ISSN: 1097-4199.

Pantel J, Williams SY, Mi D, Sebag J, Corbin JD, Weaver CD, Cone RD. Development of a high throughput screen for allosteric modulators of melanocortin-4 receptor signaling using a real time cAMP assay. Eur. J. Pharmacol [print-electronic]. 2011 Jun 6/11/2011; 660(1): 139-47. PMID: 21296065, PMCID: PMC3175485, PII: S0014-2999(11)00089-6, DOI: 10.1016/j.ejphar.2011.01.031, ISSN: 1879-0712.

Renquist BJ, Lippert RN, Sebag JA, Ellacott KL, Cone RD. Physiological roles of the melanocortin MC3 receptor. Eur. J. Pharmacol [print-electronic]. 2011 Jun 6/11/2011; 660(1): 13-20. PMID: 21211527, PMCID: PMC3095771, PII: S0014-2999(10)01286-0, DOI: 10.1016/j.ejphar.2010.12.025, ISSN: 1879-0712.

Schiöth HB, Västermark Å, Cone RD. Reply to Braasch and Postlethwait: Evolutionary origin of the teleost A2 agouti genes (agouti signaling protein 2 and agouti-related protein 2) remains unclear [letter]. Proc. Natl. Acad. Sci. U.S.A. 2011 Mar 3/29/2011; 108(13): E49-50. PMID: 21568014, PMCID: PMC3069206, ISSN: 1091-6490.

Ghamari-Langroudi M, Cone RD. Shining a light on energy homeostasis. Cell Metab. 2011 Mar 3/2/2011; 13(3): 235-6. PMID: 21356511, PMCID: PMC3073614, PII: S1550-4131(11)00051-9, DOI: 10.1016/j.cmet.2011.02.007, ISSN: 1932-7420.

Srisai D, Gillum MP, Panaro BL, Zhang XM, Kotchabhakdi N, Shulman GI, Ellacott KL, Cone RD. Characterization of the hyperphagic response to dietary fat in the MC4R knockout mouse. Endocrinology [print-electronic]. 2011 Mar; 152(3): 890-902. PMID: 21239438, PMCID: PMC3040060, PII: en.2010-0716, DOI: 10.1210/en.2010-0716, ISSN: 1945-7170.

Ghamari-Langroudi M, Srisai D, Cone RD. Multinodal regulation of the arcuate/paraventricular nucleus circuit by leptin. Proc. Natl. Acad. Sci. U.S.A [print-electronic]. 2011 Jan 1/4/2011; 108(1): 355-60. PMID: 21169216, PMCID: PMC3017160, PII: 1016785108, DOI: 10.1073/pnas.1016785108, ISSN: 1091-6490.

Ghamari-Langroudi M, Vella KR, Srisai D, Sugrue ML, Hollenberg AN, Cone RD. Regulation of thyrotropin-releasing hormone-expressing neurons in paraventricular nucleus of the hypothalamus by signals of adiposity. Mol. Endocrinol [print-electronic]. 2010 Dec; 24(12): 2366-81. PMID: 20943814, PMCID: PMC2999480, PII: me.2010-0203, DOI: 10.1210/me.2010-0203, ISSN: 1944-9917.

Zhang C, Song Y, Thompson DA, Madonna MA, Millhauser GL, Toro S, Varga Z, Westerfield M, Gamse J, Chen W, Cone RD. Pineal-specific agouti protein regulates teleost background adaptation. Proc. Natl. Acad. Sci. U.S.A [print-electronic]. 2010 Nov 11/23/2010; 107(47): 20164-71. PMID: 20980662, PMCID: PMC2996689, PII: 1014941107, DOI: 10.1073/pnas.1014941107, ISSN: 1091-6490.

Date Y, Mondal MS, Kageyama H, Ghamari-Langroudi M, Takenoya F, Yamaguchi H, Shimomura Y, Mori M, Murakami N, Shioda S, Cone RD, Nakazato M. Neuropeptide W: an anorectic peptide regulated by leptin and metabolic state. Endocrinology [print-electronic]. 2010 May; 151(5): 2200-10. PMID: 20189998, PII: en.2009-1153, DOI: 10.1210/en.2009-1153, ISSN: 1945-7170.

Gruber KA, Fan W, Akerberg H, Larhammar D, Chee MJ, Colmers WF, Cone RD. Neuropeptide Y and gamma-melanocyte stimulating hormone (gamma-MSH) share a common pressor mechanism of action. Endocrine [print-electronic]. 2009 Jun; 35(3): 312-24. PMID: 19363600, PMCID: PMC2714906, DOI: 10.1007/s12020-008-9141-3, ISSN: 1355-008X.

Sutton GM, Perez-Tilve D, Nogueiras R, Fang J, Kim JK, Cone RD, Gimble JM, Tschöp MH, Butler AA. The melanocortin-3 receptor is required for entrainment to meal intake. J. Neurosci. 2008 Nov 11/26/2008; 28(48): 12946-55. PMID: 19036988, PMCID: PMC2613653, PII: 28/48/12946, DOI: 10.1523/JNEUROSCI.3615-08.2008, ISSN: 1529-2401.

Ellacott KL, Murphy JG, Marks DL, Cone RD. Obesity-induced inflammation in white adipose tissue is attenuated by loss of melanocortin-3 receptor signaling. Endocrinology [print-electronic]. 2007 Dec; 148(12): 6186-94. PMID: 17901224, PII: en.2007-0699, DOI: 10.1210/en.2007-0699, ISSN: 0013-7227.

Forlano PM, Cone RD. Conserved neurochemical pathways involved in hypothalamic control of energy homeostasis. J. Comp. Neurol. 2007 Nov 11/20/2007; 505(3): 235-48. PMID: 17879270, DOI: 10.1002/cne.21447, ISSN: 0021-9967.

Song Y, Cone RD. Creation of a genetic model of obesity in a teleost. FASEB J [print-electronic]. 2007 Jul; 21(9): 2042-9. PMID: 17341684, PII: fj.06-7503com, DOI: 10.1096/fj.06-7503com, ISSN: 1530-6860.

Voss-Andreae A, Murphy JG, Ellacott KL, Stuart RC, Nillni EA, Cone RD, Fan W. Role of the central melanocortin circuitry in adaptive thermogenesis of brown adipose tissue. Endocrinology [print-electronic]. 2007 Apr; 148(4): 1550-60. PMID: 17194736, PII: en.2006-1389, DOI: 10.1210/en.2006-1389, ISSN: 0013-7227.

Cone RD. Studies on the physiological functions of the melanocortin system. Endocr. Rev [print-electronic]. 2006 Dec; 27(7): 736-49. PMID: 17077189, PII: er.2006-0034, DOI: 10.1210/er.2006-0034, ISSN: 0163-769X.

Ni XP, Butler AA, Cone RD, Humphreys MH. Central receptors mediating the cardiovascular actions of melanocyte stimulating hormones. J. Hypertens. 2006 Nov; 24(11): 2239-46. PMID: 17053546, PII: 00004872-200611000-00019, DOI: 10.1097/01.hjh.0000249702.49854.fa, ISSN: 0263-6352.

Mak RH, Cheung W, Cone RD, Marks DL. Mechanisms of disease: Cytokine and adipokine signaling in uremic cachexia. Nat Clin Pract Nephrol. 2006 Sep; 2(9): 527-34. PMID: 16941045, PII: ncpneph0273, DOI: 10.1038/ncpneph0273, ISSN: 1745-8323.

Ellacott KL, Cone RD. The role of the central melanocortin system in the regulation of food intake and energy homeostasis: lessons from mouse models. Philos. Trans. R. Soc. Lond., B, Biol. Sci. 2006 Jul 7/29/2006; 361(1471): 1265-74. PMID: 16815803, PMCID: PMC1642695, PII: M99357886476M867, DOI: 10.1098/rstb.2006.1861, ISSN: 0962-8436.

Ellacott KL, Halatchev IG, Cone RD. Characterization of leptin-responsive neurons in the caudal brainstem. Endocrinology [print-electronic]. 2006 Jul; 147(7): 3190-5. PMID: 16601142, PII: en.2005-0877, DOI: 10.1210/en.2005-0877, ISSN: 0013-7227.

Mak RH, Cheung W, Cone RD, Marks DL. Leptin and inflammation-associated cachexia in chronic kidney disease. Kidney Int. 2006 Mar; 69(5): 794-7. PMID: 16518340, PII: 5000182, DOI: 10.1038/sj.ki.5000182, ISSN: 0085-2538.

Morgan C, Cone RD. Melanocortin-5 receptor deficiency in mice blocks a novel pathway influencing pheromone-induced aggression. Behav. Genet [print-electronic]. 2006 Mar; 36(2): 291-300. PMID: 16408249, DOI: 10.1007/s10519-005-9024-9, ISSN: 0001-8244.

Ellacott KL, Halatchev IG, Cone RD. Interactions between gut peptides and the central melanocortin system in the regulation of energy homeostasis. Peptides [print-electronic]. 2006 Feb; 27(2): 340-9. PMID: 16309792, PII: S0196-9781(05)00446-8, DOI: 10.1016/j.peptides.2005.02.031, ISSN: 0196-9781.

Marks DL, Hruby V, Brookhart G, Cone RD. The regulation of food intake by selective stimulation of the type 3 melanocortin receptor (MC3R). Peptides [print-electronic]. 2006 Feb; 27(2): 259-64. PMID: 16274853, PMCID: PMC1679957, PII: S0196-9781(05)00437-7, DOI: 10.1016/j.peptides.2005.01.025, ISSN: 0196-9781.

Ghamari-Langroudi M, Colmers WF, Cone RD. PYY3-36 inhibits the action potential firing activity of POMC neurons of arcuate nucleus through postsynaptic Y2 receptors. Cell Metab. 2005 Sep; 2(3): 191-9. PMID: 16154101, PII: S1550-4131(05)00231-7, DOI: 10.1016/j.cmet.2005.08.003, ISSN: 1550-4131.

Cheung W, Yu PX, Little BM, Cone RD, Marks DL, Mak RH. Role of leptin and melanocortin signaling in uremia-associated cachexia. J. Clin. Invest. 2005 Jun; 115(6): 1659-65. PMID: 15931394, PMCID: PMC1136984, DOI: 10.1172/JCI22521, ISSN: 0021-9738.

Cone RD. Anatomy and regulation of the central melanocortin system. Nat. Neurosci. 2005 May; 8(5): 571-8. PMID: 15856065, PII: nn1455, DOI: 10.1038/nn1455, ISSN: 1097-6256.

Halatchev IG, Cone RD. Peripheral administration of PYY(3-36) produces conditioned taste aversion in mice. Cell Metab. 2005 Mar; 1(3): 159-68. PMID: 16054059, PII: S1550-4131(05)00056-2, DOI: 10.1016/j.cmet.2005.02.003, ISSN: 1550-4131.

Available Postdoctoral Position Details
The laboratory is interested in attracting outstanding postdoctoral fellows interested in research on the central control of energy homeostasis. We are currently looking for scientists with experience in 1) GPCR pharmacology and drug discovery, 2) zebrafish genetics, 3) mouse modeling using tissue specific gene targeting, and 4) bioinformatics and whole exome sequencing and analysis.