Humboldt State University, Arcata, CA, 1980 BA Biology
Purdue University, West Lafayette, IN, 1985 PhD Molecular Biology
The Johns Hopkins School of Medicine, Baltimore, MD, 1989 Post Doc Neuroscience
1989-1997: Assistant Professor, University of Miami School of Medicine, Department of Physiology and Biophysics
1997-2003: Assoc. Professor, University of Miami School of Medicine, Department of Physiology and Biophysics
1990-2003: Faculty Member, Neuroscience Program, University of Miami School of Medicine
1991-2003: Secondary Appointment, Department of Biochemistry and Molecular Biology, University of Miami School of Medicine
2000-2003: Member, University of Miami School of Medicine Cancer Center, Tumor Cell Biology Program
2003-present: Associate Professor, University of Rochester School of Medicine, Department of Neurobiology and Anatomy
2003-present: Secondary Appointment, University of Rochester School of Medicine, Department of Physiology and Pharmacology
1987-1989 NIH NRSA Individual Postdoctoral Fellowship Award
1994-1995 Stanley Glaser Research Award, University of Miami School of Medicine
1996 UM Dean's Award for Excellence in Research and Creativity; Outstanding Graduate Mentor
Patient Care Bio
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.