Dr. Robert A. Kesterson, completed his undergraduate studies in Chemistry at Hendrix College, and received a Ph.D. in Cell Biology from Baylor College of Medicine (1993) under the mentorship of Dr. J. Wesley Pike and Dr. Francesco DeMayo. His postdoctoral training in the field of neuroendocrinology was carried out at The Vollum Institute for Advanced Biomedical Research, Portland, Oregon with Dr. Roger D. Cone, which focused on determining the function of newly cloned melanocortin receptors via development of transgenic animal models. Dr. Kesterson was appointed in 1997 to the faculty of Vanderbilt University in the Department of Molecular Physiology & Biophysics, and was then recruited to UAB in 2004.
Dr. Kesterson is the Director of the UAB Transgenic Mouse Facility, and is a member of several UAB Centers including: Comprehensive Cancer Center, Arthritis & Musculoskeletal Center, Clinical Nutrition Research Center, Recessive Polycystic Kidney Disease Core Center, Civitan International Research Center, Diabetes Research & Training Center, and Center for Metabolic Bone Disease.
Hypothalamic Control of Feeding Behavior
The main goal of Dr. Kesterson’s research is to define the mechanisms and neural pathways by which CNS melanocortin receptors regulate the feeding, energy balance, thermoregulation, inflammation, and learning and memory. Disruption of CNS melanocortin signaling due to loss of function mutations in the POMC gene (which makes the ligand a-MSH) or the type 4 melanocortin receptor (MC4R) produces obesity in humans and other mammals. Several approaches are currently being utilized to define the location of the neural circuitry by which a-MSH, MC4R, and MC3R (a related receptor involved with maintaining energy balance) function, including: creating conditional melanocortin receptor knockout animals using the cre/loxP recombinase system, developing transgenic mice expressing GFP, LacZ, and luciferase reporter transgenes to functionally map basal and brain-specific enhancer elements, and using microarray analyses and Real-Time RT-PCR to characterize changes in gene expression due to weight gain stemming from atypical antipsychotic medications (AAPDs). More recently, research has focused on mechanisms by which primary cilium localized on hypothalamic neurons regulate energy balance. Dr. Kesterson also is working with a group of investigators to establish a mouse model for reconstituting human hematopoietic systems. To this end, double-knockout mice lacking Recombination Activating Gene (RAG) and the IL-2 receptor common g chain (gc) genes (which are unable to develop B, T or NK cells to mount a response to human cells) are being replenished with human CD34+ hematopoietic stem cells from cord blood or from GM-CSF-mobilized CD34+ peripheral blood cells from adult patients. Directors of the Flow Cytometry and High Speed Cell Sorting facility, and the Hematopoietic Stem Cell facility have pooled their expertise to establish this unique animal model. Additional mouse models under development in the Kesterson laboratory for translational research include common nonsense and missense mutations found in Neurofibromatosis-1 patients. Graduate Biomedical Science Themes: # Cancer Biology # Cell, Molecular and Developmental Biology # Genetics and Genomic Sciences # Neuroscience
- Ni, X, Kesterson, R.A., Hruby, V.J., Cone, R.D., Wiedemann, E., and Humphreys, M.H. Prevention of Natriuresis After Acute Unilateral Nephrectomy (AUN) by a Melanocortin 3 Receptor (MC3-R) Antagonist (1998) American Journal of Physiology 274: R931-R938 9575953
- Clemens, T.L., Tang, H., Maeda, S., Kesterson, R.A., Demayo, F., Pike, J.W., Gundberg, C.M. Analysis of osteocalcin expression in transgenic mice reveals a species difference in vitamin D regulation of mouse and human osteocalcin genes (1997) Bone Miner Res:1570-1576 9333117
- *Miyamoto, K., *Kesterson R.A., Yamamoto, H., Taketani, Y., Nishiwaki, E., Tatsumi, S., Inoue, Y., Morita, K., Takeda, E., Pike, J.W. Structural organization of the human vitamin D receptor chromosomal gene and its promoter (1997) Molecular Endocrinology:1165-1179 *Co-first author 9212063
- Kesterson, R.A., Huszar, D., Simerly, R.B., and Cone, R.D. Induction of Neuropeptide Y Gene Expression in the Dorsal Medial Hypothalamic Nucleus in Two Models of the Agouti Obesity Syndrome (1997) Molecular Endocrinology 11:630-637 9139806
- Huszar, D., Lynch, C.A., Fairchild-Huntress, V., Dunmore, J.H., Smith, F.J., Kesterson, R.A., Boston, B.A., Fang, Q., Berkemeier, L.R., Gu, W., Cone, R.D., Campfield, L.A., Lee, F. Recapitulation of the Agouti Obesity Syndrome in Mice Lacking the Melanocortin-4 Receptor (1997) Cell 88:131-141 9019399
- Fan, W., Boston,B.A., Kesterson, R.A., Hruby, V.J., and Cone, R.D. Melanocortinergic Inhibition of Feeding Behavior and Disruption with an Agouti-mimetic (1997) Nature 385:165-168 8990120
- Li, Si-Jia, Varga, K., Archer, P., Hruby, V.J., Sharma, S.D., Kesterson, R.A., Cone, R.D., and Kunos, G. Melanocortin Antagonists Define Two Distinct Pathways of Cardiovascular Control by a- and g-Melanocyte-Stimulating Hormones (1996) Journal of Neuroscience 16:5182-5188 8756446
- Cone, R.D., Lu, D.L., Chen, W., Koppula, S., Inge Vage, D., Klungland, H., Boston, B., Orth, D.N., Pouton, C., and Kesterson, R.A. The Melanocortin Receptors: Agonists, Antagonists, and the Hormonal Control of Pigmentation (1996) Recent Progress in Hormone Research 51:287-318 8701084
- Kesterson, R.A., DeMayo, F., Stanley, L., Finegold, M.J., and Pike, J.W. Vitamin D Regulation of Human Osteocalcin Gene Expression in Transgenic Mice (1993) Molecular Endocrinology 7:462-467 8483481
- Friedman, D.L., Kesterson, R.A., Puleo, P., Wu, A.H.B., and Perryman, M.B. Recombinant Creatine Kinase Proteins as Standards for Creatine Kinase Isoenzyme and Subform Assays (1993) Clinical Chemistry 39:1598-1601 8353943
- Hruby, V.J.., Lu, D.L, Sharma, S.D., Castrucci, A., Kesterson, R.A., Al-Obeidi, F.A., Hadley, M.E., and Cone, R.D. Cyclic Lactam a-Melanotropin Analogues of Ac-Nle4-cyclo[Asp5, D-Phe7,Lys10] a-Melanocyte-Stimulating Hormone-(4-10)-NH2 with Bulky Aromatic Amino Acids at Position 7 Show High Antagonist Potency and Selectivity at Specific Melanocortin Receptors (1995) Journal of Medicinal Chemistry 38:3454-3461 7658432
- Stenzel, P., Kesterson, R.A., Yeung, W., Cone, R.D., Rittenberg, M.B., and Stenzel-Poore, M.P. Identification of a Novel Murine Receptor for Corticotropin-Releasing Hormone Expressed in the Heart (1995)Molecular Endocrinology 9:637-645 7565810
- Hughes, M., Malloy, P., Kieback, D., Kesterson, R.A., Pike, J.W., Feldman, D., and O'Malley, B.W. Point Mutations in the Human Vitamin D Receptor Gene Associated with Hypocalcemic Rickets (1988) Science 242:1702-1705 2849209
- O'Connor AK, Kesterson RA, Yoder BK. Generating conditional mutants to analyze ciliary functions: the use of Cre-lox technology to disrupt cilia in specific organs. Methods Cell Biol. 2009;93:305-30. Epub 2009 Dec 4. 20409823
- Morabito MV, Abbas AI, Hood JL, Kesterson RA, Jacobs MM, Kump DS, Hachey DL, Roth BL, Emeson RB. Mice with altered serotonin 2C receptor RNA editing display characteristics of Prader-Willi syndrome. Neurobiol Dis. 2010 Aug;39(2):169-80. Epub 2010 Apr 13. 20394819
- Kesterson RA, Berbari NF, Pasek RC, Yoder BK. Utilization of conditional alleles to study the role of the primary cilium in obesity. Methods Cell Biol. 2009;94:163-79. Epub 2009 Dec 23. Review. 20362090
- Cope, M.B., Jumbo-Luciono, P., Allison, D.B., DiCostanzo, C.A., Jamison, W.G., Kesterson, R.A., and Nagy, T.R. Risperidone alters food intake, core body temperature and locomotor activity in mice. Physiol Behav 2009 Mar 2;96(3):457-63 19084548
- Kumar KG, Trevaskis JL, Lam DD, Sutton GM, Koza RA, Chouljenko VN, Kousoulas KG, Rogers PM, Kesterson RA, Thearle M, Ferrante AW Jr, Mynatt RL, Burris TP, Dong JZ, Halem HA, Culler MD, Heisler LK, Stephens JM, Butler AA. Identification of adropin as a secreted factor linking dietary macronutrient intake with energy homeostasis and lipid metabolism.
Cell Metab. 2008 Dec;8(6):468-81. 19041763
- Brooks WS, Helton ES, Banerjee S, Venable M, Johnson L, Schoeb TR, Kesterson RA, Crawford DF. G2E3 is a dual function ubiquitin ligase required for early embryonic development.
J Biol Chem. 2008 Aug 8;283(32):22304-15. Epub 2008 May 28. 18511420
- Zinn, K.R., Chaudhuri, T.R., Szafran, A.A., OQuinn, D., Weaver, C., Dugger, K., Lamar, D., Kesterson, R.A., Wang, X., and Stuart, F.J. Noninvasive bioluminescence imaging in small animals. ILAR J. 2008;49(1):103-15 18172337
- Chen M, Aprahamian CJ, Kesterson RA, Harmon CM, Yang Y.Molecular Identification of the Human Melanocortin-2 Receptor Responsible for Ligand Binding and Signaling. Biochemistry. 2007 Oct 9;46(40):11389-97. Epub 2007 Sep 18 17877367
- Davenport, JR, Watts, AJ, Roper VC, Croyle MJ, van Groen T, Wyss JM, Nagy TR, Kesterson RA, Yoder BK. Disruption of intraflagellar transport in adult mice leads to obesity and slow-onset cystic kidney disease. Curr Biol. 2007 Sep 18;17(18):1586-94. 17825558
- Yang, Y., Chen, M., Kesterson, R.A., and Harmon, C.M. Structural insights into the role of the ACTH receptor cysteine residues on receptor function, AJP 2007 293(3):R1120-6 17596328
- Singh, M., Kesterson, R.A., Joers, J.M, Jamison, W., Gore, J.C., and Emeson, R.B. Expression of the RNA editing enzyme ADAR2 leads to hyperphagia-mediated obesity in transgenic mice, JBC 2007 3;282(31):22448-59. 17567573
- Cope, M.B., Jumbo-Lucioni, P., Walton, R.G., Kesterson, R.A., Allison, D.B., and Nagy, T.R. No effect of dietary fat on short-term weight gain in mice treated with atypical antipsychotic drugs, Int J Obes (Lond). 2007 Jun;31(6):1014-22. Epub 2007 Jan 16. 17224931
- He, S, Schoeb, T.R., Panoskaltsis-Mortari, A., Zinn, K.R., Kesterson, R.A., Zhang, J., Samuel, S., Hicks, M.J., and Bullard, D.C. Deficiency of P-selectin or PSGL-1 Leads to Accelerated Development of Glomerulonephritis and Increased Expression of CCL2 in Lupus-Prone Mice (2006) J. Immunology 177(12):8748-56 17142777
- Jones, J.R., Barrick, C., Blondeau, B., Fujimoto, Y., Shiota, M., Kesterson, R.A., Kahn, B.B., and Magnuson. M.A. Deletion of PPARγ in adipose tissues of mice protects against high fat diet-induced obesity and insulin resistance. (2005) PNAS 102(17):6207-12 15833818
- Ercil, N.E., Galici, R., McDonald, M., and Kesterson, R.A. HS014, a selective melanocortin-4 receptor (MC4R) antagonist, enhances the behavioral effects of morphine. (2005) Psychopharmacology 180(2):279-85 15719225
- Lamar, C.R., Jamison, W., Brazda, A., Kesterson, R.A. Putative Targets of CNS Melanocortin Receptors (2003) Ann N Y Acad Sci. 994:211-7 12851318
- Sutcliffe, J.S., Han, M.K., Amin, T., Kesterson, R.A., Nurmi, E.L. Partial Duplication of the APBA2 Gene in Chromosome 15q13 Corresponds to Duplicon Structures (2003) BMC Genomics 4(1):15 12720574
- Butler, A.A., Kesterson, R.A., Khong, K., Cullen, M.J., Pelleymounter, M.A., Dekoning, J., Baetscher, M., Cone, R.D. A Unique Metabolic Syndrome Causes Obesity in the Melanocortin-3 Receptor-Deficient Mouse (2000) Endocrinology 141:3518-21 10965927
- *Coste, S.C., *Kesterson, R.A., Heldwein, K.A., Stevens, S.L., Hill, J.K., Heard, A.D., Murray, S.E., Pantely, G.A., Hohimer, A.R., Hatton, D.C., Phillips, T.J., Finn, D.A., Low, M.J., Rittenberg, M.B., Stenzel, P., Stenzel-Poore, M.P. Aberrant Appetite Control and Impaired Cardiovascular Function in Mice Lacking Corticotropin-Releasing Hormone Receptor-2 (2000) Nature Genetics 24:403-409 *Co-first author 10742107
- Ashley, J.W., Shi, Z., Zhao, H., Li, X., Kesterson, R.A., and Feng, X. Genetic Ablation of CD68 Results in Mice with Increased Bone and Dysfunctional Osteoclasts, PLoS ONE, 2011;6(10):e25838. Epub 2011 Oct 3
- Berbari, N.F., Kin, N.W., Sharma, N., Michaud, E.J., Kesterson, R.A., and Yoder, B.K. Mutations in Traf3ip1 reveal defects in ciliogenesis, embryonic development, and altered cell size regulation, Dev Biol. 2011 Sep 16
- Liu, Z., Swindall, A.F., Bullard, D.C., Kesterson, R.A., Schoeb, T.R., and Bellis, S.L. ST6Gal-I regulates macrophage apoptosis via α2-6 sialylation of the TNFR1 death receptor. J Biol Chem. 2011 Sep 19.