Julio E. Ayala, Ph.D.

Associate Professor

Faculty Appointments
Associate Professor of Molecular Physiology & Biophysics
Ph.D., Molecular Physiology & Biophysics, Vanderbilt University, Nashville, TennesseeB.S., Chemistry/Biochemistry, Duke University, Durham, North Carolina
Research Description
Research in the Ayala lab focuses on gut-brain interactions that regulate energy balance. Specifically, we are interested in identifying regions in the central nervous system and molecular mechanisms within those regions that mediate the effects of the gut hormone Glucagon-like peptide-1 (Glp1) and related Glp1 receptor (Glp1r) agonists on feeding behavior. Our lab combines transgenic mouse models, targeted pharmacological interventions and state-of-the-art metabolic phenotyping capabilities to address research questions. We aim to extend the technical expertise in the lab to leverage the existing imaging, circuit mapping, electrophysiology and behavioral phenotyping capabilities at Vanderbilt. Other projects in the lab focus on leveraging biochemical and pharmacological properties of the Glp1r towards the design of more effective therapeutics for obesity and diabetes.
Research Keywords
Glucagon-like peptide-1, obesity, diabetes, energy balance, brain, transgenic mouse models, metabolic phenotyping, neuroscience
Steiner A, Owen BM, Bauer JP, Seanez L, Kwon S, Biddinger JE, Huffman R, Ayala JE, Nobis WP, Lewis AS. Glucagon-like peptide-1 receptor differentially controls mossy cell activity across the dentate gyrus longitudinal axis. Hippocampus [print-electronic]. 2022 Nov; 32(11-12): 797-807. PMID: 36063105, PMCID: PMC9675713, DOI: 10.1002/hipo.23469, ISSN: 1098-1063.

Bales MB, Centanni SW, Luchsinger JR, Fathi P, Biddinger JE, Le TDV, Nwaba KG, Paldrmic IM, Winder DG, Ayala JE. High fat diet blunts stress-induced hypophagia and activation of Glp1r dorsal lateral septum neurons in male but not in female mice. Mol Metab [print-electronic]. 2022 Oct; 64: 101571. PMID: 35953023, PMCID: PMC9418981, PII: S2212-8778(22)00140-5, DOI: 10.1016/j.molmet.2022.101571, ISSN: 2212-8778.

Zhang X, Luo S, Wang M, Huang Q, Fang W, Li J, Liu T, Zhang Y, Deng Z, Liu CL, Guan S, Ayala JE, Flavell RA, Kulkarni RN, Libby P, Guo J, Liu Z, Shi GP. IL18 signaling causes islet ß cell development and insulin secretion via different receptors on acinar and ß cells. Dev Cell [print-electronic]. 2022 Jun 6/20/2022; 57(12): 1496-1511.e6-1511.e6. PMID: 35675813, PMCID: PMC9233156, PII: S1534-5807(22)00370-7, DOI: 10.1016/j.devcel.2022.05.013, ISSN: 1878-1551.

Ayala JE, Lantier L, McGuinness OP, Wasserman DH. Peeling back the layers of the glucose clamp. Nat Metab. 2022 May; 4(5): 496-8. PMID: 35477775, PII: 10.1038/s42255-022-00573-1, DOI: 10.1038/s42255-022-00573-1, ISSN: 2522-5812.

Yong J, Parekh VS, Reilly SM, Nayak J, Chen Z, Lebeaupin C, Jang I, Zhang J, Prakash TP, Sun H, Murray S, Guo S, Ayala JE, Satin LS, Saltiel AR, Kaufman RJ. Chop/Ddit3 depletion in ß cells alleviates ER stress and corrects hepatic steatosis in mice. Sci Transl Med. 2021 Jul 7/28/2021; 13(604): PMID: 34321322, PMCID: PMC8557800, PII: 13/604/eaba9796, DOI: 10.1126/scitranslmed.aba9796, ISSN: 1946-6242.

Burmeister MA, Brown JD, Ayala JE, Stoffers DA, Sandoval DA, Seeley RJ, Ayala JE. The Glucagon-Like Peptide-1 Receptor in the Ventromedial Hypothalamus Reduces Short-Term Food Intake in Male Mice by Regulating Nutrient Sensor Activity. Am. J. Physiol. Endocrinol. Metab [print-electronic]. 2017 Aug 8/15/2017; ajpendo.00113.2017. PMID: 28811293, PII: ajpendo.00113.2017, DOI: 10.1152/ajpendo.00113.2017, ISSN: 1522-1555.

Brown JD, Karimian Azari E, Ayala JE. Oleoylethanolamide: A fat ally in the fight against obesity. Physiol. Behav [print-electronic]. 2017 Jul 7/1/2017; 176: 50-8. PMID: 28254531, PII: S0031-9384(16)31199-4, DOI: 10.1016/j.physbeh.2017.02.034, ISSN: 1873-507X.

Lee S, Leone TC, Rogosa L, Rumsey J, Ayala J, Coen PM, Fitts RH, Vega RB, Kelly DP. Skeletal muscle PGC-1ß signaling is sufficient to drive an endurance exercise phenotype and to counteract components of detraining in mice. Am. J. Physiol. Endocrinol. Metab [print-electronic]. 2017 May 5/1/2017; 312(5): E394-E406. PMID: 28270443, PMCID: PMC5451529, PII: ajpendo.00380.2016, DOI: 10.1152/ajpendo.00380.2016, ISSN: 1522-1555.

Burmeister MA, Ayala JE, Smouse H, Landivar-Rocha A, Brown JD, Drucker DJ, Stoffers DA, Sandoval DA, Seeley RJ, Ayala JE. The Hypothalamic Glucagon-Like Peptide 1 Receptor Is Sufficient but Not Necessary for the Regulation of Energy Balance and Glucose Homeostasis in Mice. Diabetes [print-electronic]. 2017 Feb; 66(2): 372-84. PMID: 27908915, PMCID: PMC5248999, PII: db16-1102, DOI: 10.2337/db16-1102, ISSN: 1939-327X.

Mulvihill EE, Varin EM, Gladanac B, Campbell JE, Ussher JR, Baggio LL, Yusta B, Ayala J, Burmeister MA, Matthews D, Bang KWA, Ayala JE, Drucker DJ. Cellular Sites and Mechanisms Linking Reduction of Dipeptidyl Peptidase-4 Activity to Control of Incretin Hormone Action and Glucose Homeostasis. Cell Metab [print-electronic]. 2017 Jan 1/10/2017; 25(1): 152-65. PMID: 27839908, PII: S1550-4131(16)30538-1, DOI: 10.1016/j.cmet.2016.10.007, ISSN: 1932-7420.

Smith KR, Hussain T, Karimian Azari E, Steiner JL, Ayala JE, Pratley RE, Kyriazis GA. Disruption of the sugar-sensing receptor T1R2 attenuates metabolic derangements associated with diet-induced obesity. Am. J. Physiol. Endocrinol. Metab [print-electronic]. 2016 Apr 4/15/2016; 310(8): E688-E698. PMID: 26884387, PMCID: PMC4835941, PII: ajpendo.00484.2015, DOI: 10.1152/ajpendo.00484.2015, ISSN: 1522-1555.

Kim GH, Szabo A, King EM, Ayala J, Ayala JE, Altarejos JY. Leptin recruits Creb-regulated transcriptional coactivator 1 to improve hyperglycemia in insulin-deficient diabetes. Mol Metab. 2015 Mar; 4(3): 227-36. PMID: 25737949, PMCID: PMC4338314, PII: S2212-8778(14)00207-5, DOI: 10.1016/j.molmet.2014.12.006, ISSN: 2212-8778.

Younce CW, Niu J, Ayala J, Burmeister MA, Smith LH, Kolattukudy P, Ayala JE. Exendin-4 improves cardiac function in mice overexpressing monocyte chemoattractant protein-1 in cardiomyocytes. J. Mol. Cell. Cardiol [print-electronic]. 2014 Nov; 76: 172-6. PMID: 25200599, PMCID: PMC4250388, PII: S0022-2828(14)00279-X, DOI: 10.1016/j.yjmcc.2014.08.022, ISSN: 1095-8584.

Reddy IA, Wasserman DH, Ayala JE, Hasty AH, Abumrad NN, Galli A. Striatal dopamine homeostasis is altered in mice following Roux-en-Y gastric bypass surgery. ACS Chem Neurosci [print-electronic]. 2014 Oct 10/15/2014; 5(10): 943-51. PMID: 25068716, PMCID: PMC4324416, DOI: 10.1021/cn500137d, ISSN: 1948-7193.

Burmeister MA, Ayala J, Drucker DJ, Ayala JE. Central glucagon-like peptide 1 receptor-induced anorexia requires glucose metabolism-mediated suppression of AMPK and is impaired by central fructose. Am. J. Physiol. Endocrinol. Metab [print-electronic]. 2013 Apr 4/1/2013; 304(7): E677-85. PMID: 23341495, PII: ajpendo.00446.2012, DOI: 10.1152/ajpendo.00446.2012, ISSN: 1522-1555.

Younce CW, Burmeister MA, Ayala JE. Exendin-4 attenuates high glucose-induced cardiomyocyte apoptosis via inhibition of endoplasmic reticulum stress and activation of SERCA2a. Am. J. Physiol., Cell Physiol [print-electronic]. 2013 Mar; 304(6): C508-18. PMID: 23302777, PII: ajpcell.00248.2012, DOI: 10.1152/ajpcell.00248.2012, ISSN: 1522-1563.

Burmeister MA, Bracy DP, James FD, Holt RM, Ayala J, King EM, Wasserman DH, Drucker DJ, Ayala JE. Regulation of glucose kinetics during exercise by the glucagon-like peptide-1 receptor. J. Physiol. (Lond.) [print-electronic]. 2012 Oct 10/15/2012; 590(20): 5245-55. PMID: 22890715, PMCID: PMC3497575, PII: jphysiol.2012.234914, DOI: 10.1113/jphysiol.2012.234914, ISSN: 1469-7793.

Berglund ED, Li CY, Ayala JE, McGuinness OP, Wasserman DH. Regulation of endogenous glucose production in glucose transporter 4 over-expressing mice. PLoS ONE [print-electronic]. 2012; 7(12): e52355. PMID: 23285006, PMCID: PMC3524103, PII: PONE-D-12-27582, DOI: 10.1371/journal.pone.0052355, ISSN: 1932-6203.

Gan Z, Burkart-Hartman EM, Han DH, Finck B, Leone TC, Smith EY, Ayala JE, Holloszy J, Kelly DP. The nuclear receptor PPARß/d programs muscle glucose metabolism in cooperation with AMPK and MEF2. Genes Dev [print-electronic]. 2011 Dec 12/15/2011; 25(24): 2619-30. PMID: 22135324, PMCID: PMC3248683, PII: gad.178434.111, DOI: 10.1101/gad.178434.111, ISSN: 1549-5477.

Ayala JE, Bracy DP, Malabanan C, James FD, Ansari T, Fueger PT, McGuinness OP, Wasserman DH. Hyperinsulinemic-euglycemic clamps in conscious, unrestrained mice. J Vis Exp. 2011 Nov 11/16/2011; (57): PMID: 22126863, PMCID: PMC3308587, PII: 3188, DOI: 10.3791/3188, ISSN: 1940-087X.

Lee-Young RS, Ayala JE, Fueger PT, Mayes WH, Kang L, Wasserman DH. Obesity impairs skeletal muscle AMPK signaling during exercise: role of AMPKa2 in the regulation of exercise capacity in vivo. Int J Obes (Lond) [print-electronic]. 2011 Jul; 35(7): 982-9. PMID: 21079619, PMCID: PMC3049903, PII: ijo2010220, DOI: 10.1038/ijo.2010.220, ISSN: 1476-5497.

Kang L, Ayala JE, Lee-Young RS, Zhang Z, James FD, Neufer PD, Pozzi A, Zutter MM, Wasserman DH. Diet-induced muscle insulin resistance is associated with extracellular matrix remodeling and interaction with integrin alpha2beta1 in mice. Diabetes. 2011 Feb; 60(2): 416-26. PMID: 21270253, PMCID: PMC3028340, PII: 60/2/416, DOI: 10.2337/db10-1116, ISSN: 1939-327X.

Wasserman DH, Kang L, Ayala JE, Fueger PT, Lee-Young RS. The physiological regulation of glucose flux into muscle in vivo. J. Exp. Biol. 2011 Jan 1/15/2011; 214(Pt 2): 254-62. PMID: 21177945, PMCID: PMC3008632, PII: 214/2/254, DOI: 10.1242/jeb.048041, ISSN: 1477-9145.

Ayala JE, Bracy DP, James FD, Burmeister MA, Wasserman DH, Drucker DJ. Glucagon-like peptide-1 receptor knockout mice are protected from high-fat diet-induced insulin resistance. Endocrinology [print-electronic]. 2010 Oct; 151(10): 4678-87. PMID: 20685876, PMCID: PMC2946144, PII: en.2010-0289, DOI: 10.1210/en.2010-0289, ISSN: 1945-7170.

Ayala JE, Samuel VT, Morton GJ, Obici S, Croniger CM, Shulman GI, Wasserman DH, McGuinness OP, . Standard operating procedures for describing and performing metabolic tests of glucose homeostasis in mice. Dis Model Mech [print-electronic]. 2010 Sep; 3(9-10): 525-34. PMID: 20713647, PMCID: PMC2938392, PII: dmm.006239, DOI: 10.1242/dmm.006239, ISSN: 1754-8411.

Lee-Young RS, Ayala JE, Hunley CF, James FD, Bracy DP, Kang L, Wasserman DH. Endothelial nitric oxide synthase is central to skeletal muscle metabolic regulation and enzymatic signaling during exercise in vivo. Am. J. Physiol. Regul. Integr. Comp. Physiol [print-electronic]. 2010 May; 298(5): R1399-408. PMID: 20200137, PMCID: PMC2867517, PII: 00004.2010, DOI: 10.1152/ajpregu.00004.2010, ISSN: 1522-1490.

McGuinness OP, Ayala JE, Laughlin MR, Wasserman DH. NIH experiment in centralized mouse phenotyping: the Vanderbilt experience and recommendations for evaluating glucose homeostasis in the mouse. Am. J. Physiol. Endocrinol. Metab [print-electronic]. 2009 Oct; 297(4): E849-55. PMID: 19638507, PMCID: PMC2763792, PII: 90996.2008, DOI: 10.1152/ajpendo.90996.2008, ISSN: 1522-1555.

Lee-Young RS, Griffee SR, Lynes SE, Bracy DP, Ayala JE, McGuinness OP, Wasserman DH. Skeletal muscle AMP-activated protein kinase is essential for the metabolic response to exercise in vivo. J. Biol. Chem [print-electronic]. 2009 Sep 9/4/2009; 284(36): 23925-34. PMID: 19525228, PMCID: PMC2781986, PII: M109.021048, DOI: 10.1074/jbc.M109.021048, ISSN: 0021-9258.

Wasserman DH, Ayala JE, McGuinness OP. Lost in translation. Diabetes. 2009 Sep; 58(9): 1947-50. PMID: 19720822, PMCID: PMC2731517, PII: 58/9/1947, DOI: 10.2337/db09-0537, ISSN: 1939-327X.

Ayala JE, Bracy DP, James FD, Julien BM, Wasserman DH, Drucker DJ. The glucagon-like peptide-1 receptor regulates endogenous glucose production and muscle glucose uptake independent of its incretin action. Endocrinology [print-electronic]. 2009 Mar; 150(3): 1155-64. PMID: 19008308, PMCID: PMC2654733, PII: en.2008-0945, DOI: 10.1210/en.2008-0945, ISSN: 1945-7170.

Ayala JE, Bracy DP, Hansotia T, Flock G, Seino Y, Wasserman DH, Drucker DJ. Insulin action in the double incretin receptor knockout mouse. Diabetes [print-electronic]. 2008 Feb; 57(2): 288-97. PMID: 17977951, PII: db07-0704, DOI: 10.2337/db07-0704, ISSN: 1939-327X.

Fueger PT, Li CY, Ayala JE, Shearer J, Bracy DP, Charron MJ, Rottman JN, Wasserman DH. Glucose kinetics and exercise tolerance in mice lacking the GLUT4 glucose transporter. J. Physiol. (Lond.) [print-electronic]. 2007 Jul 7/15/2007; 582(Pt 2): 801-12. PMID: 17495042, PMCID: PMC2075340, PII: jphysiol.2007.132902, DOI: 10.1113/jphysiol.2007.132902, ISSN: 0022-3751.

Ayala JE, Bracy DP, Julien BM, Rottman JN, Fueger PT, Wasserman DH. Chronic treatment with sildenafil improves energy balance and insulin action in high fat-fed conscious mice. Diabetes [print-electronic]. 2007 Apr; 56(4): 1025-33. PMID: 17229936, PII: db06-0883, DOI: 10.2337/db06-0883, ISSN: 0012-1797.

Ayala JE, Bracy DP, McGuinness OP, Wasserman DH. Considerations in the design of hyperinsulinemic-euglycemic clamps in the conscious mouse. Diabetes. 2006 Feb; 55(2): 390-7. PMID: 16443772, PII: 55/2/390, ISSN: 0012-1797.

Wasserman DH, Ayala JE. Interaction of physiological mechanisms in control of muscle glucose uptake. Clin. Exp. Pharmacol. Physiol. 2005 Apr; 32(4): 319-23. PMID: 15810999, PII: CEP4191, DOI: 10.1111/j.1440-1681.2005.04191.x, ISSN: 0305-1870.

Ayala JE, Boustead JN, Chapman SC, Svitek CA, Oeser JK, Robey RB, O'Brien RM. Insulin-mediated activation of activator protein-1 through the mitogen-activated protein kinase pathway stimulates collagenase-1 gene transcription in the MES 13 mesangial cell line. J. Mol. Endocrinol. 2004 Aug; 33(1): 263-80. PMID: 15291758, ISSN: 0952-5041.

Ayala JE, Streeper RS, Svitek CA, Goldman JK, Oeser JK, O'Brien RM. Accessory elements, flanking DNA sequence, and promoter context play key roles in determining the efficacy of insulin and phorbol ester signaling through the malic enzyme and collagenase-1 AP-1 motifs. J. Biol. Chem [print-electronic]. 2002 Aug 8/2/2002; 277(31): 27935-44. PMID: 12032154, PII: M203682200, DOI: 10.1074/jbc.M203682200, ISSN: 0021-9258.

Hornbuckle LA, Edgerton DS, Ayala JE, Svitek CA, Oeser JK, Neal DW, Cardin S, Cherrington AD, O'Brien RM. Selective tonic inhibition of G-6-Pase catalytic subunit, but not G-6-P transporter, gene expression by insulin in vivo. Am. J. Physiol. Endocrinol. Metab. 2001 Oct; 281(4): E713-25. PMID: 11551847, ISSN: 0193-1849.

O'Brien RM, Streeper RS, Ayala JE, Stadelmaier BT, Hornbuckle LA. Insulin-regulated gene expression. Biochem. Soc. Trans. 2001 Aug; 29(Pt 4): 552-8. PMID: 11498027, ISSN: 0300-5127.

Ayala JE, Streeper RS, Desgrosellier JS, Durham SK, Suwanichkul A, Svitek CA, Goldman JK, Barr FG, Powell DR, O'Brien RM. Conservation of an insulin response unit between mouse and human glucose-6-phosphatase catalytic subunit gene promoters: transcription factor FKHR binds the insulin response sequence. Diabetes. 1999 Sep; 48(9): 1885-9. PMID: 10480625, ISSN: 0012-1797.

Chapman SC, Ayala JE, Streeper RS, Culbert AA, Eaton EM, Svitek CA, Goldman JK, Tavar JM, O'Brien RM. Multiple promoter elements are required for the stimulatory effect of insulin on human collagenase-1 gene transcription. Selective effects on activator protein-1 expression may explain the quantitative difference in insulin and phorbol ester action. J. Biol. Chem. 1999 Jun 6/25/1999; 274(26): 18625-34. PMID: 10373474, ISSN: 0021-9258.

Streeper RS, Chapman SC, Ayala JE, Svitek CA, Goldman JK, Cave A, O'Brien RM. A phorbol ester-insensitive AP-1 motif mediates the stimulatory effect of insulin on rat malic enzyme gene transcription. Mol. Endocrinol. 1998 Nov; 12(11): 1778-91. PMID: 9817602, DOI: 10.1210/mend.12.11.0199, ISSN: 0888-8809.

Available Postdoctoral Position Details
Posted: 10/5/2017

Post-doctoral positions are available in the Ayala lab studying gut-brain interactions and the control of feeding behavior via the central nervous system. The focus of the research in the lab is to identify brain regions and mechanisms that mediate the effects of the gut hormone glucagon-like peptide-1 (Glp1) on homeostatic and reward feeding. We are currently using transgenic mouse models combined with state-of-the-art metabolic phenotyping capabilities but are looking for candidates that can expand the capabilities in the lab to include techniques such as chemo/optogenetics, imaging, neural tracing, electrophysiology and behavioral analyses. The Ayala lab is located in the Department of Molecular Physiology and Biophysics at Vanderbilt University and will have access to space and resources within the Vanderbilt Center for Addiction Research, the Vanderbilt Brain Institute and the Vanderbilt Mouse Metabolic Phenotyping Center. Projects in the lab include assessments of molecular mechanisms in the hypothalamus that mediate energy balance phenotypes of Glp1 receptor (Glp1r) agonists (funded by a R01), control of dopaminergic neurotransmission by Glp1r agonists in nigrostriatal regions and novel brain regions/mechanisms targeted by Glp1r agonists that may regulate reward feeding and motivated behavior. Another project in the lab focuses on biased signaling via the Glp1r as a means to modulate phenotypic outcomes (funded by an ADA award). Candidates should have a Ph.D. in Neuroscience, Pharmacology, Psychology, Physiology or related discipline. Experience with molecular biology and one or more neuroscience techniques (chemo/optogenetics, imaging, neural tracing, electrophysiology and behavioral analyses) is especially desirable. Please send CV with names of 3 references and a statement of research interest that focuses on how your previous experience fits within the description of the Ayala lab interests to julio.e.ayala@vanderbilt.edu