The mammalian nervous system is composed of approximately 10 to the 11th different neurons each of which make very specific connections to other neurons or effector organs. Dr. Arthur Brown initially focused his research on the function of Eph receptors in axon guidance. Using embryonic stem cell technologies, he has engineered mice with altered Eph receptor expression and helped to prove the Eph receptors guide axons to their synaptic targets. The unexpected finding that one of the Eph receptor mouse mutants has a severe heart defect, allowed Dr. Brown to extend his studies of Eph receptors into the field of cardiac development and to demonstrate that the molecular control of cell movements and morphogenesis in the heart and developing nervous system are conserved.
More recently, Dr. Brown has combined his interests in neurological disease and neurodevelopment by initiating studies to address the role of embryonic genetic programs in regeneration and recovery from spinal cord injury. Dr. Brown has two major projects investigating therapeutic strategies to effect repair and regeneration after spinal cord injury. The first project is focused on manipulating gene expression in the injured spinal cord to up-regulate the expression of regeneration-promoting genes and to down-regulate the expression of regeneration-inhibiting genes.
The second project is based on the premise that stem cells, by virtue of their embryonic nature, may be able to rejuvenate and effect repair in the injured spinal cord. In this exciting project, bone marrow-derived stem cells are being evaluated for their potential therapeutic effect on regeneration and repair after spinal cord injury.
• Brown, A., Ricci, M.J. and Weaver, L.C. (2007) . NGF mRNA is expressed in the dorsal root ganglia after spinal cord injury in the rat. Experimental Neurology , Feb 3; [Epub ahead of print] PMID: 17335812.
• Gris, P., Tighe, A., Levin, D., Sharma, R. and Brown, A. (2007) . Transcriptional regulation of scar gene expression in primary astrocytes. Glia : in press.
• Stephen, L.E., Fawkes, A., Pniak, K., Pniak, A., Lemke, G., and Brown, A. (2007) A critical role for the EphA3 receptor tyrosine kinase in heart development. Developmental Biology 302: 66-79.
• Brown, A., Jacob, J.E., (2006) . Autonomic Dysreflexia in mouse models of spinal cord injury: strain differences, genetics and mechanisms in autonomic dysfunction after spinal cord injury. Progress in Brain Research 152: 299-313.
• Jacob, J.E., Gris, P., Fehlings, M.G., Weaver, L.C. and Brown, A. (2003) Automatic dysreflexia after spinal cord transection and compression in 129Sv, c57BL and Wallerian degeneration slow mutant mice. Experimental Neurology 183: 136-146.
• Vaidya, A., Pniak, A., Lemke, G. and Brown, A. (2003) . Epha3 Null Mutants do not Demonstrate Motor Axon Guidance Defects. Molecular and Cellular Biology 23: 8092-8098.
• Gris, P., Murphy, S., Jacob, J.E., Atkinson, I. and Brown, A. (2003) . Differential Gene Expression Profiles in Embryonic, Adult-Injured and Adult-Uninjured Spinal Cords. MCN , 24: 555-567.
• Brown, A., Yates, P., Burrola, P., Ortuno, D., Vaidya, A., Jessell, T.M., Pfaff, S., O'Leary, D.D.M. and Lemke, G. (2000) . Topographic innervation from the retina to the brain is controlled by relative but not absolute levels of EphA receptor signalling. Cell 102: 77-88.