Graduate Studies Faculty
Philip F. Copenhaver, Ph.D.
Programs:Cell & Developmental Biology
Neuroscience Graduate Program
Program in Molecular & Cellular Biosciences
Research Interests:developmental, Neurobiology of Disease, biology, developmental neurobiology, nervous system, neurodegeneration, neuroscience, signal transduction, cell migration, cell adhesion, in vivo imaging, embryogenesis, embryology, Ephrins, Eph receptors, Ig-CAMs, G proteins, non-receceptor tyrosine kinases, Amyloid Precursor Protein, Alzheimer's Disease, biology of aging » Click here for more about Dr. Copenhaver's research » PubMed Listing
Preceptor RotationsAcademic Term Available Summer 2016 Maybe Fall 2016 No Winter 2016 Maybe Spring 2016 Maybe
Faculty MentorshipDr. Copenhaver might be available as a mentor for 2016-2017.
Ph.D., University of Washington, 1985
Associate Professor, Cell & Developmental Biology
After undergraduate studies at Stanford University, Philip Copenhaver attended graduate school in the Department of Zoology at the University of Washington in Seattle, where he received his Ph.D. with Dr. James Truman in 1985. He spent three years as a post-doctoral fellow with Dr. Paul Taghert in the Department of Anatomy and Neurobiology at Washington University Medical School in St. Louis, and an additional year with Dr. William Moody at the University of Washington. He joined the Department of Cell and Developmental Biology at Oregon Health & Science University in 1990 as an Assistant Professor and was promoted to Associate Professor in 1996.
My research is focused on the role of disease-associated genes in the control of cell migration, with an emphasis on the developing nervous system. During the formation of the nervous system, most neurons must migrate over extensive distances to reach their correct locations. Errors in migration can give rise to serious congenital brain defects and lead to a variety of neurological diseases, including mental retardation and epilepsy. These same transduction pathways continue to be important in the adult brain, and their disruption may play important roles in a variety of neurodegenerative conditions. What are the molecular mechanisms that regulate this process? How do neurons integrate positive and negative stimuli into coherent changes in their behavior? And how do specific disruptions in migration impact the form and function of the nervous system? Because the complexity of mammalian brain has made answering these questions difficult, we have developed a “model systems” approach, exploiting the relative simplicity of insect nervous systems to investigate the control of neuronal migration within developing embryos. This strategy allows us to explore the role of evolutionarily conserved guidance receptors and ligands that guide motile neurons in both invertebrates and vertebrates, and that may be defective in a variety of diseases affecting the human brain. Using embryonic preparations of Manduca sexta (tobacco hornworm) that permit direct access to the nervous system, we can inject individual neurons with fluorescent markers for time-lapse imaging, synthetic RNAs to induce the expression of candidate genes, and antisense constructs to inhibit gene expression at specific times during development. As a complementary strategy, we use genetic manipulations in Drosophila to test the role of specific guidance receptors and signal transduction pathways regulate neuronal guidance and differentiation in developing embryos. In addition, we employ complementary in vitro assays (including primary neuronal cultures and neuroblastoma cells) to delineate specific transduction pathways that control cell motility and guidance.
A current emphasis is the role of Amyloid Precursor Proteins (APPs) in regulating neuronal motility, a function that may be perturbed in Alzheimer’s disease. In collaboration with faculty in the departments of Neurology, Pathology, and Genetics, we have established an integrated suite of bioassays to test compounds that may ameliorate amyloid toxicity. A second project addresses novel signaling mechanisms of GPI-linked Ephrins in response to Eph receptors (originally identified as oncogenes), and their modulation of Src family kinases during development and tumor invasiveness. Yet another class of guidance receptors called Ig-CAMs promotes neuronal development in the both the insect and vertebrate nervous system, and we have discovered that different versions of the same Ig-CAM (Fasciclin II) regulate distinct aspects of migration and axon outgrowth by interacting with previously unrecognized signaling pathways. By using a combination of model systems with different experimental advantages, we can explore the role of evolutionarily conserved mechanisms that control neuronal migration, providing the framework for testing how similar signaling mechanisms may be disrupted in developmental disorders that affect the mammalian nervous system.
Collaborations: with Dr. Doris Kretzschmar (CROET and MMG): Investigating the developmental role of amyloid precursor proteins (APPs) in the nervous system; identifying the mechanisms controlling the trafficking and processing of APP and its derivatives, including amyloid peptides associated with Alzheimer’s Disease; with Dr. Randy Woltjer (Pathology) and Dr. Joseph Quinn (Neurology): investigating how disruptions in the normal functions of APP and its derivatives may contribute to the pathology of Alzheimer’s Disease and related neurological conditions; with Dr. Michael Forte (Vollum Institute and CDB): Investigating the developmental role of heterotrimeric G proteins in the nervous system; how perturbations in G protein-dependent signaling may contribute to developmental defects, using insect nervous system for molecular genetic and cell biological manipulations in the embryo.