Ian Dickerson
| Title | Associate Professor |
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| Institution | School of Medicine and Dentistry |
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| Department | Neurobiology and Anatomy |
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| Address | University of Rochester Medical Center School of Medicine and Dentistry 601 Elmwood Ave, Box 603 Rochester NY 14642
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| Title | Associate Professor |
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| Institution | School of Medicine and Dentistry |
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| Department | Pharmacology and Physiology |
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| 1983 |
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| 1985 | David Ross Graduate Research Fellowship | Purdue University | | 1987 |
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| 1989 | NIH NRSA Individual Postdoctoral Fellowship Award | | 1994 |
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| Stanley Glaser Research Award | University of Miami | | 1996 |
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| Dean's Award for Excellence in Research and Creativity; Outstanding Graduate Mentor |
RESEARCH:
Signal Transduction at Neuropeptide Receptors:
Our laboratory studies the neuropeptide calcitonin gene-related peptide (CGRP). Originally discovered as an alternatively-spliced variant of the calcitonin mRNA, CGRP is one of the most potent vasodilators known. As a vasodilator, CGRP has both peripheral and central effects. One of the most notable effects of CGRP is its causative effect of migraine on the cerebral vasculature, and stable synthetic antagonists have been recently developed and are in Stage III clinical trials for migraine treatment. CGRP also suppresses immune function, is involved in pain perception, and has further central role in the development of tolerance to opiates. Recently, we have discovered that CGRP is a potent stimulator of glioma and metastatic breast cancer tumor cell growth. In collaboration with Dr. Edward Brown (Biomedical Engineering) we have observed remarkable increases in tumor cell growth rates in response to CGRP incubation. These data suggest that the CGRP receptor system represents an important new target for these types of cancer for which therapy is currently limited. The CGRP receptor is unique for G protein-coupled receptors (GPCR) in that it requires three proteins for function: calcitonin-like receptor (CLR), a stereotypical GPCR with 7 hydrophobic transmembrane domains; receptor activity modifying protein (RAMP1), a single transmembrane accessory protein that targets CLR to the cell surface and confers pharmacologic specificity, and CGRP receptor component protein (RCP) which couples the CLR/RAMP1 complex to the cellular signaling pathway. Our laboratory is investigating the mechanism of RCP action by: (1) determining the molecular/ biochemical requirements for RCP function, (2) determining the proteins that interact with RCP in a functional receptor complex using proteomic strategies, (3) determining the role of RCP and CGRP in vivo, using targeted homologous recombination to generate transgenic RCP knockout mice. In addition, we are applying the biochemical reagents made in the first three areas of interest to directly test the role of the CGRP receptor in glioma and breast cancer proliferation, with the long-term goal of identifying novel protein interactions required for CGRP receptor function as targets for future anti-cancer drug development.
RECENT PUBLICATIONS:
Ma W, Chabot JG, Powell KJ, Jhamandas K, Dickerson IM, Quirion R. (2003) "Localization and modulation of calcitonin gene-related peptide-receptor component protein-immunoreactive cells in the rat central and peripheral nervous systems." Neuroscience. 120(3):677-94. Lai, Y.C., Shaftel, S.S,, Miller, J.N., Tallents, R.H., Pinkert, C.A., Olschowka, J.A., Dickerson, I.M., Puzas, J. E., O'Banion, M. K., Kyrkanides, S. (2006). "Intraarticular induction of interleukin-1beta expression in the adult mouse, with resultant temporomandibular joint pathologic changes, dysfunction, and pain" Arthritis Rheum. 54:1184-1197. Zhang, Z., Dickerson, I.M., Russo, A.F. (2006) "CGRP Receptor Activation by RAMP1 Gene Transfer to Vascular Smooth Muscle Cells" Endocrinol. 147(4):1932-40. Tolun, A.A., Dickerson, I.M., Malhotra, A. (2006). "Overexpression and purification of human calcitonin gene-related peptide-receptor component protein in Escherichia coli". Protein Expr Purif. 52:167-174. Glaser, S., Ueno, Y., DeMorrow, S., Chiasson, V., Katki, K., Venter, J., Francis, H., Dickerson, I.M., DiPette, D., Supowit, S., Alpini, G. (2007) "Knockout of Alpha Calcitonin Gene-Related Peptide Prevents Cholangiocyte Proliferation Induced by Extrahepatic Bile Duct Obstruction" Lab. Invest;87(9):914-26. Morara S, Wang LP, Filippov V, Dickerson IM, Grohovaz F, Provini L, Kettenmann H. (2008). "Calcitonin gene-related peptide (CGRP) triggers Ca2+ responses in cultured astrocytes and in Bergmann glial cells from cerebellar slices" Eur J Neurosci. 28:2213-20.
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Egea SC, Dickerson IM. Direct Interactions between Calcitonin-Like Receptor (CLR) and CGRP-Receptor Component Protein (RCP) Regulate CGRP Receptor Signaling. Endocrinology. 2012 Apr; 153(4):1850-60.
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Supowit SC, Katki KA, Hein TW, Gupta P, Kuo L, Dickerson IM, Dipette DJ. Vascular reactivity to calcitonin gene-related peptide is enhanced in subtotal nephrectomy-salt induced hypertension. Am J Physiol Heart Circ Physiol. 2011 Sep; 301(3):H683-8.
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Morara S, Wang LP, Filippov V, Dickerson IM, Grohovaz F, Provini L, Kettenmann H. Calcitonin gene-related peptide (CGRP) triggers Ca2+ responses in cultured astrocytes and in Bergmann glial cells from cerebellar slices. Eur J Neurosci. 2008 Dec; 28(11):2213-20.
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Glaser SS, Ueno Y, DeMorrow S, Chiasson VL, Katki KA, Venter J, Francis HL, Dickerson IM, DiPette DJ, Supowit SC, Alpini GD. Knockout of alpha-calcitonin gene-related peptide reduces cholangiocyte proliferation in bile duct ligated mice. Lab Invest. 2007 Sep; 87(9):914-26.
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Tolun AA, Dickerson IM, Malhotra A. Overexpression and purification of human calcitonin gene-related peptide-receptor component protein in Escherichia coli. Protein Expr Purif. 2007 Mar; 52(1):167-74.
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Lai YC, Shaftel SS, Miller JN, Tallents RH, Chang Y, Pinkert CA, Olschowka JA, Dickerson IM, Puzas JE, O'Banion MK, Kyrkanides S. Intraarticular induction of interleukin-1beta expression in the adult mouse, with resultant temporomandibular joint pathologic changes, dysfunction, and pain. Arthritis Rheum. 2006 Apr; 54(4):1184-97.
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Zhang Z, Dickerson IM, Russo AF. Calcitonin gene-related peptide receptor activation by receptor activity-modifying protein-1 gene transfer to vascular smooth muscle cells. Endocrinology. 2006 Apr; 147(4):1932-40.
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Rossi SG, Dickerson IM, Rotundo RL. Localization of the calcitonin gene-related peptide receptor complex at the vertebrate neuromuscular junction and its role in regulating acetylcholinesterase expression. J Biol Chem. 2003 Jul 4; 278(27):24994-5000.
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Ma W, Chabot JG, Powell KJ, Jhamandas K, Dickerson IM, Quirion R. Localization and modulation of calcitonin gene-related peptide-receptor component protein-immunoreactive cells in the rat central and peripheral nervous systems. Neuroscience. 2003; 120(3):677-94.
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Hay DL, Poyner D, Dickerson I. CGRP receptor heterogeneity: a role for receptor component protein? Trends Endocrinol Metab. 2003 Jan; 14(1):3-4; author reply 4-6.
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Prado MA, Evans-Bain B, Dickerson IM. Receptor component protein (RCP): a member of a multi-protein complex required for G-protein-coupled signal transduction. Biochem Soc Trans. 2002 Aug; 30(4):460-4.
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Pokabla MJ, Dickerson IM, Papka RE. Calcitonin gene-related peptide-receptor component protein expression in the uterine cervix, lumbosacral spinal cord, and dorsal root ganglia. Peptides. 2002 Mar; 23(3):507-14.
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Prado MA, Evans-Bain B, Oliver KR, Dickerson IM. The role of the CGRP-receptor component protein (RCP) in adrenomedullin receptor signal transduction. Peptides. 2001 Nov; 22(11):1773-81.
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Krajewski JL, Dickerson IM, Potter LT. Site-directed mutagenesis of m1-toxin1: two amino acids responsible for stable toxin binding to M(1) muscarinic receptors. Mol Pharmacol. 2001 Oct; 60(4):725-31.
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Oliver KR, Kane SA, Salvatore CA, Mallee JJ, Kinsey AM, Koblan KS, Keyvan-Fouladi N, Heavens RP, Wainwright A, Jacobson M, Dickerson IM, Hill RG. Cloning, characterization and central nervous system distribution of receptor activity modifying proteins in the rat. Eur J Neurosci. 2001 Aug; 14(4):618-28.
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Evans BN, Rosenblatt MI, Mnayer LO, Oliver KR, Dickerson IM. CGRP-RCP, a novel protein required for signal transduction at calcitonin gene-related peptide and adrenomedullin receptors. J Biol Chem. 2000 Oct 6; 275(40):31438-43.
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Rosenblatt MI, Dahl GP, Dickerson IM. Characterization and localization of the rabbit ocular calcitonin gene-related peptide (CGRP)-receptor component protein (RCP). Invest Ophthalmol Vis Sci. 2000 Apr; 41(5):1159-67.
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Lindberg I, Tu B, Muller L, Dickerson IM. Cloning and functional analysis of C. elegans 7B2. DNA Cell Biol. 1998 Aug; 17(8):727-34.
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Naghashpour M, Rosenblatt MI, Dickerson IM, Dahl GP. Inhibitory effect of calcitonin gene-related peptide on myometrial contractility is diminished at parturition. Endocrinology. 1997 Oct; 138(10):4207-14.
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Sarkar A, Dickerson IM. Cloning, characterization, and expression of a calcitonin receptor from guinea pig brain. J Neurochem. 1997 Aug; 69(2):455-64.
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Gómez-Saladín E, Luebke AE, Wilson DL, Dickerson IM. Isolation of a cDNA encoding a Kex2-like endoprotease with homology to furin from the nematode Caenorhabditis elegans. DNA Cell Biol. 1997 May; 16(5):663-9.
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Rosenblatt MI, Dickerson IM. Endoproteolysis at tetrabasic amino acid sites in procalcitonin gene-related peptide by pituitary cell lines. Peptides. 1997; 18(4):567-76.
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Luebke AE, Dahl GP, Roos BA, Dickerson IM. Identification of a protein that confers calcitonin gene-related peptide responsiveness to oocytes by using a cystic fibrosis transmembrane conductance regulator assay. Proc Natl Acad Sci U S A. 1996 Apr 16; 93(8):3455-60.
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Luebke AE, Dickerson IM, Muller KJ. In situ hybridization reveals transient laminin B-chain expression by individual glial and muscle cells in embryonic leech central nervous system. J Neurobiol. 1995 May; 27(1):1-14.
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Gómez-Saladín E, Wilson DL, Dickerson IM. Isolation and in situ localization of a cDNA encoding a Kex2-like prohormone convertase in the nematode Caenorhabditis elegans. Cell Mol Neurobiol. 1994 Feb; 14(1):9-25.
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Amin J, Dickerson IM, Weiss DS. The agonist binding site of the gamma-aminobutyric acid type A channel is not formed by the extracellular cysteine loop. Mol Pharmacol. 1994 Feb; 45(2):317-23.
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Dickerson IM, Mains RE. Cell-type specific posttranslational processing of peptides by different pituitary cell lines. Endocrinology. 1990 Jul; 127(1):133-40.
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Andres DA, Dickerson IM, Dixon JE. Variants of the carboxyl-terminal KDEL sequence direct intracellular retention. J Biol Chem. 1990 Apr 15; 265(11):5952-5.
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Dickerson IM, Dixon JE, Mains RE. Biosynthesis and posttranslational processing of site-directed endoproteolytic cleavage mutants of pro-neuropeptide Y in mouse pituitary cells. J Biol Chem. 1990 Feb 15; 265(5):2462-9.
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Dickerson IM, Peden KW, Mains RE. Metallothionein-I promoter-directed expression of foreign proteins in a mouse pituitary corticotrope tumor cell line. Mol Cell Endocrinol. 1989 Jul; 64(2):205-12.
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Eipper BA, Park LP, Dickerson IM, Keutmann HT, Thiele EA, Rodriguez H, Schofield PR, Mains RE. Structure of the precursor to an enzyme mediating COOH-terminal amidation in peptide biosynthesis. Mol Endocrinol. 1987 Nov; 1(11):777-90.
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Dickerson IM, Dixon JE, Mains RE. Transfected human neuropeptide Y cDNA expression in mouse pituitary cells. Inducible high expression, peptide characterization, and secretion. J Biol Chem. 1987 Oct 5; 262(28):13646-53.
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