Associate professor in Physiology and Molecular Neurobiology
Director, CHDMM
11085 Campus Street, Mortensen Hall 132
Loma Linda, California 92350
Phone: (909) 558-8777
Fax (909) 558-0177
Email: madeleon@llu.edu
PhD (Physiology): University of California at Davis, 1987
Postdoctoral fellow (molecular neurobiology): Department of Neurobiology, Stanford University School of Medicine
Research interest
My laboratory is interested in elucidating molecular mechanism important for nerve regeneration and neuronal survival after injury in both the peripheral and central nervous system. We have been using molecular cloning and cell biological approaches to address these questions. Specifically, we are studying the role of DA11/Epidermal fatty acid binding protein during neurite extension and neuronal survival. Epithelial fatty acid-binding protein (E-FABP) is up regulated in rat dorsal root ganglia after sciatic nerve crush (De Leon et al., 1996) and in differentiating neurons during development (Liu et al., 1997, 2000; Allen et al., 2001). To further investigate the mechanistic aspects of importance of E-FABP in neurons we have developed and in vitro model to investigates the role of E-FABP during nerve growth factor (NGF) mediated neurite outgrowth in PC12 cells (Allen et al., 2000). Undifferentiated PC12 cells express low levels of E-FABP, while NGF triggers a 6-fold and 8-fold induction of E-FABP mRNA and protein, respectively. Up-regulation of E-FABP mRNA occurs as early as 12 hours after NGF treatment and remains highly expressed over the course of several days, corresponding to NGF-mediated neurite outgrowth. Withdrawal of NGF leads to down-regulation of E-FABP mRNA and retraction of neurites. Immunofluorescence confocal microscopy reveals E-FABP immunoreactivity in the perinuclear cytoplasm, neurites and growth cones of NGF-differentiated cells. To examine the role of E-FABP during neurite outgrowth, PC12 cells were transfected with a constitutive antisense E-FABP vector (driven by CMV promoter) to create the E-FABP-deficient line PC12-AS. By morphometric analysis, PC12-AS cells treated for two, four and seven days with NGF exhibited statistically significant decreased neurite expression relative to control (mock-transfected) cells (Allen et al, 2000). Taken together, these data indicate that E-FABP is important in normal NGF-mediated neurite outgrowth in PC12 cells, a finding that is consistent with a potential role in axonal development and regeneration. We are presently doing several lines of experiments to determine what ligands are interacting with E-FABP and to determine whether of the over-expression of E-FABP can protect the cell against fatty acid induced neurotoxicity (Ulloth and De Leon, in preparation).
Relevant publications
De León, M., Nahin, R.L., Molina, C., De León, D.D. and Ruda, M.A. Comparison of c-jun, jun B and Jun D on RNA expression and protein in the rat dorsal root ganglia following sciatic nerve transection. Journal of Neuroscience Research 42:391-401, 1995.
Ruda, MA, Besse, D., Inagaki, S., De León, M. and Ren, K. Nitric oxide expression and regulation in the dorsal root ganglion and spinal cord. Annals New York Academy of Science, 738: 181-190, 1995.
De León, M., AA Welcher, R.H Nahin, Y. Liu, Ruda, M.A, Shooter, E.M. and C.A. Molina. Fatty Acid Binding Protein is induced in Neurons of the dorsal root ganglia after peripheral nerve injury. Journal of Neuroscience Research 44:283-292, 1996
Liu Y, Molina CA, Welcher AA, Longo LD, Marino De León. Expression of DA11, a neuronal-Injury induced fatty acid binding protein, coincides with axon growth and neuronal differentiation during central nervous system development. Journal of Neuroscience Research, 48: 551-562, 1997.
Liu Yi, LD Longo and Marino De Leon. In situ and immunocytochemical localization of E-FABP mRNA and protein during neuronal migration and differentiation in rat brain. Brain Research 852: 16-27, 2000.
Allen GW, J-W Liu and Marino De Leon. Depletion of a fatty acid-binding protein impairs neurite outgrowth in PC12 cells. Molecular Brain Research 29:315-324, 2000.
Allen GW, J-W Liu, MA Kirby and Marino De León. Induction and axonal localization of E-FABP in retinal ganglion cells is associated with axonal growth and regeneration. Journal of Neuroscience Research 66: 396-405, 2001.
Last Revised: Wed, Apr 25, 2007
