Carrie Haskell-Luevano Ph.D.
Associate Professor
Research Interests
Our laboratory focuses on the understanding of peptide hormone endocrine systems in the brain, and their involvement in feeding behavior and obesity. We utilize multidisciplinary approaches including chemistry, molecular biology, pharmacology, physiology, and neuroscience to study endocrine systems. The techniques we use to answer different research questions include combinatorial chemistry, peptide design and synthesis, receptor pharmacology and compound analysis, computer assisted molecular modeling (CAMM) , NMR spectroscopy, receptor mutagenesis and pharmacology, use of knock-out and transgenic mice, immunohistochemistry (protein expression in the brain), in situ hybridization (mRNA expression in the brain), and administration of compounds to rodents to study food consumption over time.
Selected Publications
“Melanocortin-4
Receptor-Null Mice Display Normal Affective Licking Responses to
Prototypical Taste Stimuli in a Brief-Access Test,” Eylam, S., Moore,
M., Haskell-Luevano, C., and Spector, A.C.Peptides
in press
“Ghrelin -Induced Food Intake and Growth Hormone Secretion is Altered
in Melanocortin 3 and 4 Receptor Knockout Mice,” Shaw, A.M., Irani,
B.G., Moore, M.C., Haskell-Luevano, C., and Millard, W.J. Peptides
in press
“A Review of Melanocortin Receptor Small Molecule Ligands”
Todorovic, A., and Haskell-Luevano, C. Peptides
in press
“Feeding Effects of Melanocortin Ligands- A Historical
Perspective,” Irani, B.G. and Haskell-Luevano, C., Peptides
in press
“Current Trends in the Structure-Activity Relationship Studies of the
Endogenous Agouti-Related Protein (AGRP) Melanocortin Receptor
Antagonist,” Wilczynski, A.M., Joseph, C.G., and Haskell-Luevano, C.
Medicinal Research
Reviews in press
“Overview of Endogenous and Synthetic Melanocortin Peptides,”
Wilson, K.R., Todorovic, A., Proneth, A., and Haskell-Luevano, C. Cell Mol Biol.
in press
“Voluntary Exercise Delays Monogenetic Obesity and Overcomes
Reproductive Dysfunction of the Melanocortin-4 Receptor Knockout
Mouse,” Irani, B., Xiang, Z., Moore, M.C., Mandel, R.J., and
Haskell-Luevano, C. Biochem. Biophys. Res.
Commun., 236:638-644 (2005).
“Bone Morphogenetic Protein Signaling Controls Hair Pigmentation by
Means of Cross-Talk with the Melanocortin Receptor-1 Pathway,” Sharov,
A.A., Fessing, M., Atoyan, R., Sharova, T.Y., Haskell-Luevano, C., Weiner,
L., Brissette, J.L., Gilchrest, B.A., Botchkarev, V.A. Proc. Natl. Acad.
Sci.
USA
102:93-98 (2005).
“Meal Patterns and Foraging in Melanocortin Receptor Knockout
Mice,” Vaughan, C.H., Moore, M.C., Haskell-Luevano, C., and Rowland,
N.E. Physiology &
Behavior 84:129-133 (2005).
“Structure-Activity
Relationships of the Unique and Potent Agouti Related Peptide
(AGRP)-Melanocortin Chimeric
Tyr-c[Asp-His-DPhe-Arg-Trp-Asn-Ala-Phe-Dpr]-Tyr-NH2 Peptide Template,”
Wilczynski, A., Wilson, K.R., Scott, J.W., Edison, A.S., and
Haskell-Luevano, C. J. Med. Chem.
48:3060-3075 (2005).
“N-Terminal Fatty Acylated His-DPhe-Arg-Trp-NH2
Tetrapeptides: Influence of Fatty Acid Chain Length on Potency
and Selectivity at the Mouse Melanocortin Receptors and Human
Melanocytes,” Todorovic, A., Holder, J.R., Bauzo, R.M., Scott, J.W.,
Kavanagh, R. Abdel-Malek, Z., and Haskell-Luevano, C. J. Med. Chem.
48:3328-3336 (2005).
“Structural Characterization of a
Potent (Cys101-Cys119, Cys110-Cys117) Bicyclic Agouti-Related
Protein (AGRP) Melanocortin Receptor Antagonist”, Wilczynski, A.,
Wang, X.S., Bauzo, R.M., Xiang, Z., Shaw, A.M., Millard, W.J., Richards,
N.G., Edison, A.S., and Haskell-Luevano, C. J. Med. Chem.
47:5662-5673 (2004).
“Stereochemical Studies of the
Monocyclic Agouti-Related Protein(103-122) Arg-Phe-Phe Residues: Conversion
of a Melanocortin-4 Receptor Antagonist into an Agonist and Results in the
Discovery of a Potent and Selective Melanocortin-1 Agonist,” Joseph,
C.G., Wang, X.S., Scott, J.W., Bauzo, R.M., Xiang, Z., Richards, N.G., and
Haskell-Luevano, C. J. Med. Chem.
47:6702-6710 (2004).
“The Melanocortin Pathway: Effects of
Voluntary Exercise on the Melanocortin-4 Receptor Knockout Mice and
ACTH(1-24) Ligand Structure Activity Relationships at the Melanocortin-2
Receptor,” Haskell-Luevano, C. Todorovic, A., Gridley, K. Sorenson,
N., Irani, B. and Xiang, Z. Endocrine Res. 30:591-597 (2004).
“Progress
in the Development of Melanocortin Receptor Selective Ligands,” Irani,
B.G., Holder, J.R., Todorovic, A., Wilczynski, A.M., Joseph, C.G., Wilson,
K.R., and Haskell-Luevano, C. Curr. Pharm. Design
10:3443-3479 (2004).
“Melanocortin Ligands: 30 Years of
Structure Activity Relationship (SAR) Studies,”Holder, J.R. and
Haskell-Luevano, C. Medicinal Research
Reviews 24:325-356 (2004).
“Synthesis and Activity of the Melanocortin
Xaa-DPhe-Arg-Trp-NH2 Tetrapeptides with Amide Bond
Modifications,” Todorovic, A., Holder, J.R., Scott, J.W., and
Haskell-Luevano, C. J. Peptide Res.,
63:270-278 (2004).
“Identification of Putative Agouti-Related
Protein(87-132)-Melanocortin-4 Receptor Interactions by Homology Molecular
Modeling and Validation Using Chimeric Peptide Ligands,” Wilczynski,
A., Wang, X.S., Joseph, C.G., Xiang, Z., Bauzo, R.M, Scott, J.W., Sorensen,
N.B., Shaw, A.M., Millard, W.J., Richards, N.G., and Haskell-Luevano,
C. J. Med.
Chem., 47:2197-2207 (2004).
“Chimeric NDP-MSH and MTII
Melanocortin Peptides with Agouti-Related Protein (AGRP) Arg-Phe-Phe Amino
Acids Possess Agonist Melanocortin Receptor Activity,” Joseph, C.G.,
Wilczynski, A., Holder, J.R., Xiang, Z., Bauzo, R.M, Scott, J. W., and
Haskell-Luevano, C. Peptides
24:1899-1908 (2003)
“Design and Pharmacology of Peptiods and Peptide-Peptoid Hybrids Based
on the Melanocortin Agonist Core Tetrapeptide Sequence,” Holder, J.R.,
Bauzo, R.M., Xiang, Z., Scott, J.W., and Haskell-Luevano, C. BioOrg. & Med.
Chem. Letts. 13:4505-4509 (2003).
“Urea Small Molecule Melanocortin Receptor Agonists,” Joseph,
C.G., Bauzo, R.M., Xiang, Z., and Haskell-Luevano, C. BioOrg. & Med.
Chem. Letts. 13:2079-2082 (2003).
“Elongation Studies of the Human Agouti-Related Protein (AGRP) Core
Decapeptide (Yc[CRFFNAFC]Y) Results in Antagonism at the Mouse
Melanocortin-3 Receptor,” Joseph, C.G., Bauzo, R.M., Xiang, Z., Shaw,
A.M., Millard, W.J., and Haskell-Luevano, C. Peptides,
24:263-270 (2003).
“Characterization of Aliphatic, Cyclic, and Aromatic N-Terminally
“Capped” His-DPhe-Arg-Trp-NH2 Melanocortin Tetrapeptides at the
Melanocortin Receptors,” Holder, J.R., Marques, F.F., Xiang, Z.,
Bauzo, R.M., and Haskell-Luevano, C. Eur J. Pharmacol.,
462:41-52 (2003).
“A Solid Phase Approach to Mouse
Melanocortin Receptor Agonists Derived from a Novel Thioether Cyclized
Peptidomimetic Scaffold,” Bondebjerg, J., Xiang, Z., Bauzo, R.M.,
Haskell-Luevano, C., and Meldal, M. J. Am. Chem. Soc.,
124:11046-1055 (2002).
“Structure-Activity Relationships of
the Melanocortin Tetrapeptide Ac-His-DPhe-Arg-Trp-NH2 at the
Mouse Melanocortin Receptors: Part 4 Modifications at the Trp
Position,” Holder, J.R., Xiang, Z., Bauzo, R.M., and
Haskell-Luevano, C. J. Med. Chem., 45:5736-5744 (2002).
"Structure-Activity Relationships of the Melanocortin Tetrapeptide
Ac-His-DPhe-Arg-Trp-NH2 at the Mouse Melanocortin Receptors: Part
I Modifications at the His Position," Holder, J.R., Bauzo, R.M., Xiang, Z.,
and Haskell-Luevano, C. J. Med. Chem., 45:2801-2810 (2002).
"Structure-Activity Relationships of the Melanocortin Tetrapeptide Ac-His-DPhe-Arg-Trp-NH2 at the Mouse Melanocortin Receptors: Part 2 Modifications at the Phe Position," Holder, J.R., Bauzo, R.M., Xiang, Z., and Haskell-Luevano, C. J. Med. Chem., 45:3073-3081 (2002).
"Novel Agouti-related Protein (AGRP) Based Melanocortin-1 Receptor Antagonist," Thirumoorthy, R., Holder, J.R., Bauzo, R.M., Richards, N.G.J., Edison, A.S., and Haskell-Luevano, C. J. Med. Chem., 44:4114-4124 (2001).
"Characterization of Melanocortin NDP-MSH Agonist Peptide Fragments at the Mouse Central and Peripheral Melanocortin Receptors," Haskell-Luevano, C., Holder, J.R., Monck, E.K., and Bauzo, R.M. J. Med. Chem., 44:2247-2252 (2001).
"Structure Activity Studies of the Melanocortin-4 Receptor by In Vitro Mutagenesis: Identification of Agouti-Related Protein (AGRP), Melanocortin Agonist and Synthetic Peptide Antagonist Interaction Determinants," Haskell-Luevano, C., Cone, R.D., Monck, E.K., and Wan, Y.-P. Biochemistry 40:6164-6179 (2001).
"Agouti-related Protein (AGRP) Functions as an Inverse Agonist at a Constitutively Active Brain Melanocortin-4 Receptor," Haskell-Luevano, C., and Monck, E.K. Regulatory Peptides 99:1-7 (2001).
"The Naturally Occurring Melanocortin Antagonist, Agouti-related Protein (AGRP) Possesses Similar and Distinct Interactions at the MC4 Receptor Compared with Melanocortin Agonists," Haskell-Luevano, C., Monck, E.K., and Wan, Y-P. In Proceedings of the 2nd International/17th American Peptide Symposium (Lebel, M., and Houghten, R. Eds.), Kluwer Academic Publishers, The Netherlands, pp879-880 (2001).
"Structure Activity Relationship (SAR) Studies of Melanocortin Receptor Agonists Central His-Phe-Arg-Trp Sequence," Holder, J.R., Bauzo, R.M., and Haskell-Luevano, C. In Proceedings of the 2nd International/17th American Peptide Symposium(Lebel, M., and Houghten, R. Eds.), Kluwer Academic Publishers, The Netherlands, pp706-707 (2001).
"A Novel Solid Phase Approach to Thioether Cyclized Peptides," Bondebjerg, J., Meldal, M., Haskell-Luevano, C., Bauzo, R.M. In Proceedings of the 2nd International/17th American Peptide Symposium (Lebel, M., and Houghten, R. Eds.), Kluwer Academic Publishers, The Netherlands, pp271-272 (2001).
"The Agouti-Related Protein Decapeptide (Y-c[CRFFNAFC]Y) Possess Agonist Activity at the Murine Melanocortin-1 Receptor," Haskell-Luevano, C., Monck, E.K., Wan, Y.-P., and Schentrup, A.M. Peptides 21:683-689 (2000).
"In
Vitro Mutagenesis Studies of Melanocortin Receptor Coupling and Ligand
Binding," Haskell-Luevano, C.
In The Melanocortin Receptors,
(Roger D. Cone Ed.) The Humana Press Inc., New Jersey, pp263-306 (2000).
"The Melanocortin-1 Receptor," Lu, D., Haskell-Luevano, C.,
V„ge, D.I., and Cone, R.D.
In The Melanocortin Receptors,
(Roger D. Cone Ed.) The Humana Press Inc., New Jersey, pp309-339 (2000).
"Structure Activity Studies of the Melanocortin Antagonist SHU9119 Modified at the 6,7,8, and 9 Positions," Haskell-Luevano, C. Lim, S., Yuan, W., Cone, R.D. and Hruby, V.J. Peptides 21:49-57 (2000).
"Point Mutation in the TM6 of the Melanocortin-4 Receptor Results in Agonist Activity of the MC4R Antagonist SHU9119," Haskell-Luevano, C. and Cone, R.D. In Peptides for the New Millennium, Proceedings of the Sixteenth American Peptide Symposium, (Fields, G.B., Tam, J.P., and Barany, G. Eds.), Kluwer Academic Publishers, The Netherlands, pp589-591 (2000).
"Identification of Melanocortin-1 Receptor Selective Small Molecule Agonists," Haskell-Luevano, C., Rosenquist, Å.,Souers, A. Kong, K., Ellman, J. and Cone, R.D. In Peptides for the New Millennium, Proceedings of the Sixteenth American Peptide Symposium, (Fields, G.B., Tam, J.P., and Barany, G. Eds.), Kluwer Academic Publishers, The Netherlands, pp243-244 (2000).
"Compounds that Activate the Mouse Melanocortin-1 Receptor Identified by Screening a Small Molecule Library Based upon the b-turn", Haskell-Luevano, C., Rosenquist, A., Souers, A. Khong, K., Ellman, J. and Cone, R.D. J. Med. Chem. 42:4380-4387 (1999).
"Characterization of the Neuroanatomical Distribution of Agouti Related Protein (AGRP) Immunoreactivity in the Rhesus Monkey and the Rat", Haskell-Luevano, C., Chen, P., Li, C., Chang, K., Smith, M.S., Cameron, J.L., and Cone, R.D. Endocrinology 140:1408-1415 (1999).
"Altered Expression of Agouti Related Protein (AGRP) and its Colocalization with Neuropeptide Y (NPY) in the Arcuate Nucleus of the Hypothalamus During Lactation", Chen, P., Li, C., Haskell-Luevano, C., Cone, R.D., and Smith, M.S. Endocrinology 140:2645-2650 (1999).
"Designing Potent and Selective Melanotropin Agonist and Antagonist Ligands for the Recently Discovered Melanocortin 3, 4 and 5 Receptors", Hruby, V.J., Han, G., Yuan, W., Lim, S., Haskell-Luevano, C., Hadley, M.E., Cone, R.D., and Weinberg, D.H. In Peptides 1998, Proceedings of the 25th European Peptide Symposium, (Bajusz, S. and Hudecz, F. Eds.) Akademia Kiado, Budapest, Hungary, pp70-71 (1999).
"The Melanocortin Receptors", Haskell-Luevano, C., Hadley, M.E. Drug News & Perspectives, 12:197-205 (1999).
"The Proopiomelanocortin System", Hadley, M.E., and Haskell-Luevano, C. Annals of the New York Academy of Sciences, 885:1-21 (1999).
"Design of Peptides and Peptidomimetics in Chi Space", Hruby, V.J., Li, G., Haskell-Luevano, C., and Shenderovich, M. Biopolymers Peptide Science 43:219-266 (1997).
"Functional Variants of the MSH Receptor (MC1-R), Agouti, and Their Effects on Mammalian Pigmentation", Lu, D., Haskell-Luevano, C., Vage, D.I., and Cone, R.D. In G-Proteins, Receptors, and Disease (Spiegel, A.M. Ed.) Humana Press Inc., New Jersey, pp. 231-259 (1997).
"Molecular Basis for the Interaction of [Nle4, DPhe7] Melanocyte Stimulating Hormone with the Human Melanocortin-1 Receptor (Melanocyte alpha-MSH Receptor)," Yang, Y.-K., Dickinson, C., Haskell-Luevano, C., and Gantz, I. J. Biol. Chem. 272:23000-23010 (1997).
"Biological and Conformational Evaluation of Stereochemical Modifications Using the Template Melanotropin Peptide, Ac-Nle-c[Asp-His-Phe-Arg-Trp-Ala-Lys]-NH2, on Human Melanocortin Receptors", Haskell-Luevano, C., Nikiforovich, G.V., Sharma, S.D., Yang, Y.-K., Dickinson, C., Hruby, V.J., and Gantz, I. J. Med. Chem. 40:1738-1748 (1997).
"Discovery of Prototype Peptidomimetic Agonists at the Human Melanocortin Receptors, MC1R and MC4R", Haskell-Luevano, C., Hendrata, S., North, C., Sawyer, T.K., Hadley, M.E., Hruby, V.J., Dickinson, C., and Gantz, I. J. Med. Chem. 40:2133-2139 (1997).
"beta-Methylation of Phe7 and Trp9 Melanotropin Sidechain Pharmacophores Affect Ligand-Receptor Interactions and Prolonged Biological Activity", Haskell-Luevano, C., Toth, K., Boteju, L., Job, C. Castrucci, A.M.L., Hadley, M.E. and Hruby, V.J., J. Med. Chem. 40:2750-2759 (1997).
"Characterizations of the Unusual Dissociation Properties of Melanotropin Peptides From the Melanocortin Receptor, hMC1R", Haskell-Luevano, C., Miwa, H., Dickinson, C., Hadley, M.E., Hruby, V.J., Yamada, T., and Gantz, I., J. Med. Chem., 39: 432-435 (1996).
"The Use of Topographical Constraints in Receptor Mapping: Investigation of the Topographical Requirements of the Tryptophan 30 Residue for Receptor Binding of Asp-Tyr-DPhe-Gly-Trp-(N-Me)Leu- Asp-Phe-NH2 (SNF 9007), A Cholecystokinin (26-33) Analogue That Binds toBoth CCK-B and d-Opiod Receptors",Boteju, L.W., Nikiforovich, G.V., Haskell-Luevano, C., Fang, S.-N., Zalewska, T., Stropova, D., Yamamura, H.I. and Hruby, V.J., J. Med. Chem., 39: 4120-4124 (1996).
"Truncation Studies of alpha-Melanotropin Peptides Identifies Tripeptide Analogues Exhibiting Prolonged Agonist Bioactivity", Haskell-Luevano, C., Sawyer, T.K., Hendrata, S., North, C., Panahinia, L., Stum, M., Staples, D.J., Castrucci, A.M., Hadley, M.E., and Hruby, V.J., Peptides, 17: 995-1002 (1996).
"Three-Dimensional Molecular Models of the hMC1R Melanocortin Receptor: Complexes with Melanotropin Peptide Agonists", Haskell-Luevano, C., Sawyer, T.K., Trumpp-Kallmeyer, S., Bikker, J., Humblet, C., Gantz, I. and Hruby, V.J., Drug Design & Discovery, 14:197-211 (1996).
"Melanocortin Receptors: Identification and Characterization by Melanotropic Peptide Agonists and Antagonists", Hadley, M.E., Hruby, V.J., Jiang, J., Sharma, S.D., Fink, J.L., Haskell-Luevano, C., Bentley, D.L., Al-Obeidi, F.,and Sawyer, T.K. Pigment Cell Res. 9:213-234 (1996).
"Design, Synthesis, Biology, and Conformations of Bicyclic alpha-Melanotropin Analogues", Haskell-Luevano, C., Shenderovich, M.D., Sharma, S.D., Nikiforovich, G.V., Hadley, M.E., and Hruby, V.J. J. Med. Chem., 38: 1736-1750 (1995).
"Topographical Modification of Melanotropin Peptide Analogues with beta-Methyltryptophan Isomers at Position 9 Leads to Differential Potencies and Prolonged Biological Activities", Haskell-Luevano, C., Boteju, L., Miwa, H., Dickinson, C., Gantz, I., Yamada, T., Hadley, M.E. and Hruby, V.J., J. Med. Chem., 38: 4720-4729 (1995).
"Facile Removal of the
N-Indole-Mesitylenesulfonyl Protecting Group Using HF Cleavage Conditions",
Haskell-Luevano, C., Boteju, L.W., and Hruby, V.J., Lett. in Peptide
Science, 1: 163-170 (1995).
“Binding and cAMP Studies of Melanotropin Peptides with the Cloned Human Peripheral Melanocortin Receptor, hMC1R”, Haskell-Luevano, C., Miwa, H., Dickinson, C., Hruby, V.J., Yamada, T., and Gantz, I., Biochem. Biophys. Res. Commun., 204(3): 1137-1142 (1994).
