My laboratory studies receptors and cell-signaling pathways in Schwann cells that regulate the response to peripheral nerve injury. Applying molecular, cellular, and animal model studies, we have identified low density lipoprotein receptor-related protein (LRP-1) as a major orchestrator of changes that occur in Schwann cells as they undergo phenotypic modulation in injury. LRP-1 is an endocytic protease receptor and a cell-signaling receptor that controls important pathways including the phosphatidylinositol 3-kinase/Akt pathway, the Ras-ERK/MAP kinase pathway, and the IKK/NF-kappaB pathway. LRP-1 also functions as an important regulator of inflammation. Our recent studies have identified multiple mediators of PNS injury as ligands for LRP-1 that trigger cell-signaling. Thus, a major goal of my laboratory is to understand the function of LRP-1 in glial cell survival and in the regulation of inflammation during neuropathic pain. We feel it is possible to exploit the activities of LRP-1 in the development of novel therapeutics that target chronic pain. A second receptor of great interest to this laboratory is the erythropoietin receptor (EpoR). My laboratory was the first to identify EpoR in Schwann cells and demonstrate roles for the EpoR in counteracting neuropathic pain in the injured peripheral nerve. EpoR-dependent cell-signaling in Schwann cells may inhibit the activity of pro-inflammatory cytokines. Again, there is excellent potential to exploit our growing knowledge of the function of the EpoR for therapeutic development in neuropathic pain. My laboratory is continuing its work in the area of low back pain. We were awarded one of the most prestigious honors in the area of spine research, “the ISSLS prize” for outstanding basic science research. We demonstrated that activating EpoR inhibited spinal neurons and glia from apoptosis and alleviated neuropathic pain in a model of lumbar radiculopathy. I am member of the Neurosciences Graduate Program and the Neurosciences Imaging Center. We have active collaborations with faculty in the Departments of Pathology and Orthopedics at UCSD and Chiba University. Our work is funded by R01 grants from the NINDS, NIH (see Crisp database for full description).
Example 1. Antagonizing LRP-1 with RAP induces cell death in adult nerve after axotomy in vivo. A, GST-RAP or GST was injected into rat sciatic nerves. Axotomies were then performed immediately proximal to the injection site. Nerves were harvested 24 h later. Cell death was detected in representative sections by.immunoflourescence microscopy as TUNEL-positive (green) endoneural cells. Nucleated cells are marked with Dapi (blue). The photomicrographs are representative of 2 sections examined for each of three animals per group. From Campana et al. 2006 J Neurosci
Example 2. Phosphorylated ERK1/2 (pERK1/2) in sciatic nerve after crush injury. Immunofluorescence of sciatic nerve (frozen section) using an antibody that recognizes pERK1/2. Note localization of pERK1/2 immunoreactivity in Schwann cell crescents (green). Nucleated cells are visualized with Dapi (blue).
Selected Publications
Gaultier, A., Arandjelovic, S., Li, X., Janes, J., Dragojlovic, N., Zhou, G.P., Dolkas, J., Myers, R.R., Gonias, S.L., Campana, W.M. (2008) A shed form of LDL receptor-related protein-1 regulates peripheral nerve injury and neuropathic pain in rodents. J Clin Invest 118:161-172.
Campana, W.M. (2007) Schwann cells: Activated glia and their role in neuropathic pain. Brain Behav Immun 21:522-7.
Campana, W.M., Li, X., Dragojlovic, N., Janes, J., Gaultier, A., and Gonias, S.L. (2006) The low density lipoprotein receptor-related protein is a pro-survival receptor in Schwann cells: possible implications in peripheral nerve injury. J Neurosci 26:11197-207.
Campana, W.M., Li, X., Shubayev, V.I., Angert, M., Cai, K., and Myers, R.R. (2006) Erythropoietin reduces Schwann cell TNF-a, Wallerian degeneration and painful behaviors after peripheral nerve injury. Eur J Neurosci 23:617-28.
Campana, W.M. (2006) Erythropoietin and neuroprotection in the peripheral nervous system: in vivo studies. In Erythropoietin and the Nervous System (A. Hoke, eds.) Springer, New York, NY, pp 165-177.
Li, X., Gonias, S.L., and Campana, W.M. (2005) Schwann cells express erythropoietin receptor and represent a major target for Epo in peripheral nerve injury. Glia 51:254-265.
