Ian M. Dickerson, Ph.D.

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RESEARCH:

Signal Transduction at Neuropeptide Receptors

Our laboratory works on signal transduction at the receptor for the neuropeptide calcitonin gene-related peptide (CGRP). CGRP is one of the most potent vasodilators known, and has been implicated in hypertension, migraine, and chronic pain. Despite the clinical implications of CGRP's biological actions, therapeutic strategies targeting CGRP have been hindered by the lack of an identified CGRP receptor. CGRP binding results in increased cAMP levels in cells and tissue, and a candidate G protein-coupled receptor has been identified called the calcitonin-like receptor (CLR). However, CLR was initially non-functional when transfected into mammalian tissue culture cells. We recently discovered a novel protein required for signal transduction at CGRP receptors named the CGRP-receptor component protein (RCP). RCP is a low molecular weight intracellular membrane-associated protein that couples the CGRP receptor to the cellular signal transduction pathway. RCP co-immunoprecipitates with the CGRP receptor (CLR) demonstrating a direct interaction between the two proteins. CLR also requires a second chaperone protein named receptor activating protein (RAMP1) for routing to the cell surface. Our model for a functional CGRP receptor therefore must include at least three proteins in a complex: the ligand binding protein (CLR), a chaperone protein (RAMP1), and a coupling protein for signal transduction (RCP). RCP represents a new level of regulation for signal transduction at G protein-coupled receptors.

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 usingproteomic strategies, (3) determining the role of RCP and CGRP in vivo, using targeted homologous recombination to generate transgenic RCP knockout mice.

RECENT PUBLICATIONS:

Hay DL, Poyner D, Dickerson IM. (2002) "CGRP receptor heterogeneity: a role for receptor component protein?" Trends Endocrinol Metab. 14:3-4.

Rossi SG, Dickerson IM, Rotundo RL. (2003) "Localization of the calcitonin gene-related peptide receptor complex at the vertebrate neuromuscular junction and its role in regulating acetylcholinesterase expression. J Biol Chem. 278(27):24994-5000.

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.

Current Appointments

• Associate Professor - Department of Neurobiology and Anatomy (SMD)
• Associate Professor - Department of Pharmacology and Physiology (SMD)

Education
PhD Molecular Biology	Purdue University	1985
BA Biology	Humboldt State Univ	1980

Post-Doctoral Training & Residency
The Johns Hopkins School of Medicine Neuroscience	1985 - 1989

Recent Journal Articles
Showing the 5 most recent journal articles. (33 available)
Morara, S.; Filippov, V.; Wang, L.; Dickerson, I.M.; Provini, L.; Kettenmann, H.; Grohovaz, F. ""Calcitonin Gene-Related Peptide (CGRP) triggers Ca2+ responses in cultured astrocytes and in Bergmann glial cells from cerebellar slices."". Eur J Neurosci. 28 (2008): 2213-20.
Tolun AA; Dickerson IM; Malhotra A. "Overexpression and purification of human calcitonin gene-related peptide-receptor component protein in Escherichia coli." Protein expression and purification. 2007; 52(1):167-74. Epub 2006 Sep 20.
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." Laboratory investigation; a journal of technical methods and pathology. 2007; 87(9):914-26. Epub 2007 Jul 09.
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; 147(4):1932-40. Epub 2005 Dec 22.
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 and rheumatism. 2006; 54(4):1184-97.