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.

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

Awards and Honors
Dean's Award for Excellence in Research and Creativity; Outstanding Graduate Mentor University of Miami	1996
Stanley Glaser Research Award University of Miami	1994
NIH Postdoctoral Fellowship	1987 - 1989
Purdue University David Ross Graduate Research Fellowship	1983 - 1985