W. Marie Campana, PhD

W. Marie Campana, PhD

Professor
Department of Anesthesiology
Co-Director
Center for Research in Gender in STEMM

Contact Information

Email: wcampana@ucsd.edu
Phone: 858.822.3767

Location: MTF 447

Mailing Address:
University of California, San Diego
9500 Gilman Drive #0629
La Jolla, CA 92093

CV

My laboratory studies the molecular and cellular response to nerve injury and how this relates to chronic neuropathic pain. A main focus in the lab, is the study of receptors and cell-signaling pathways in Schwann cells, the glia of peripheral nerves, and how that regulates the response to peripheral nerve injury. We have identified the low-density lipoprotein receptor-related protein (LRP1) as a major orchestrator of changes that occur in Schwann cells after nerve injury. LRP1 appears to be a novel regulator of phenotypic modulation of Schwann cells during injury. LRP1 is an endocytic and a cell-signaling receptor that controls the phosphatidylinositol 3-kinase-Akt pathways, the Ras-ERK/MAP kinase pathway, and the IKK-NFκB pathway. LRP1 also functions as a regulator of neuroinflammation. We have shown that diverse proteins implicated in PNS injury bind to LRP1, transactivate (Trks) or recruit co-receptors (NMDARs), and robustly activate Schwann cell-signaling. A major goal of my laboratory is to determine the mechanisms by which LRP1 regulates the response to PNS injury and chronic neuropathic pain. We feel it is possible to exploit the activities of LRP1 in the development of novel therapeutics that target chronic pain. We work closely with Dr. Jerry Yang in UCSD Chemistry to develop novel LRP1 therapeutics. Another receptor of great interest to this laboratory is the erythropoietin receptor (EpoR). My laboratory initially discovered that EpoR is located in peripheral nerve. We have demonstrated that activation of EpoR protects both sensory neurons and Schwann cells from apoptosis and facilitates recovery from neuropathic pain after peripheral nerve injury. We are actively investigating the role of Epo in peripheral nerve regeneration; specifically its effect on denervated Schwann cells and how expression of Epo in multi-channeled bioengineered scaffolds facilitates regeneration. Again, there is excellent potential to exploit our growing knowledge of the function of EpoR for therapeutics development in regeneration and neuropathic pain. The second main focus is investigating underlying mechanisms of severe spinal cord injury pain. We are interested in how gap junction proteins in the DRG regulate communication between sensory axons and satellite cells. My laboratory is a member of the Neurosciences Imaging Center. We have ongoing collaborations with faculty in the Departments of Pathology, Chemistry and Neurosciences at UCSD, Chiba University, Tokyo, Japan, and University of Michigan. My lab is funded by the Department of Defense and NIH/NINDS.

Mantuano E, Lam M, Shibayama M, Campana WM, Gonias SL (2015) The NMDA receptor functions independently and as an LRP1 co-receptor to promote Schwann cell survival and migration. J Cell Sci 128:3478-88

Lee-Kubli CA, Ingves M, Henry KW, Shiao R, Collyer E, Tuszynski MH, Campana, WM (2016) Analysis of the behavioral, cellular and molecular characteristics of pain in a severe rodent spinal cord injury. Experimental Neurology 278:91-104.

Gonias SL, Campana WM (2014) LDL receptor-related protein-1: A regulator of inflammation in atherosclerosis, cancer, and injury to the nervous system. Am J Path 184:18-27.

Yoon C, van Niekerk E, Henry K, Ishikawa T, Orita S, Tuszynski MH, Campana WM (2013) Low density lipoprotein receptor related protein 1 lRP1 dependent cell signaling promotes axonal regeneration. J Biol Chem 288:265557-68.

Orita S, Henry KW, Mantuano E, Yamauchi K, Ishikawa T, DeCorato A, Pollack M, Feltri ML, Wrabetz L, Ellisman M, Takahashi K, Gonias S, Campana WM (2013) Schwann cell LRP1 regulates Remak bundle ultrastructure and axonal interactions to prevent neuropathic pain. J Neurosci 33:5590-602.

Mantuano E, Henry KW, Yamauchi T, Hiramatsu N, Yamauchi K, Orita S, Takahashi K, Lin JH, Gonias SL, Campana WM (2011) The unfolded protein response is a major mechanism by which LRP1 regulates Schwann cell survival after injury. J Neurosci 31:13376-13385.

Inoue G, Gaultier A, Li XQ, Mantuano E, Richardson G, Takahashi K, Campana WM (2010) Erythropoietin promotes Schwann cell migration and assembly of the provisional extracellular matrix by recruiting β1 integrin to the cell surface. GLIA 58:399-409.

Mantuano E, Jo M, Gonias SL, Campana WM (2010) Low density lipoprotein receptor-related protein (LRP1) regulates Rac1 and RhoA reciprocally to control Schwann cell adhesion and migration. J Biol Chem 285:14259-14266.

Gaultier A, Arandjelovic S, Li X, Janes J, Dragojlovic N, Zhou GP, Dolkas J, Myers RR, Gonias SL, Campana WM (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.

Mantuano E, Inoue G, Li XQ, Takahashi K, Gaultier A, Gonias SL, Campana WM (2008) The hemopexin domain of matrix metalloproteinase-9 activates cell signaling and promotes migration of Schwann cells by binding to low density lipoprotein receptor related protein. J Neurosci 28:11571-11582

Campana WM, Li X, Dragojlovic N, Janes J, Gaultier A, Gonias SL (2006) The low density lipoprotein receptor-related protein is a pro-survival receptor in Schwann cells: possible implications in peripheral nerve injury. J Neurosci 26:11197-11207.

Li X, Gonias SL, Campana WM (2005) Schwann cells express erythropoietin receptor and represent a major target for Epo in peripheral nerve injury. Glia 51:254-265.

Campana WM, Myers RR (2001) Erythropoietin and erythropoietin receptors in the peripheral nervous system: Changes after nerve injury. FASEB J 15:804-806.