18 GOALS FOR FELLOWSHIP TRAINING AND CAREER My long-term goal is to become an independent researcher and make significant contributions to our understanding of central nervous system (CNS) trauma, specifically trauma to the spinal cord My predoctoral work focused on the initial excitotoxic events and development of chronic central pain following contusion spinal cord injury using biochemical, molecular, and behavioral outcomes However, in order to become an independent investigator of spinal cord injury, I need a greater knowledge of nerve regeneration after CNS injury During this fellowship I will examine why the CNS fails to initiate new axonai growth by evaluating expression of growth associated genes after injury This requires learning new techniques, such as in situ hybridiazation, viral vector delivery, in vitro and in rive assays of axonal growth, models of nerve regeneration and a new model of spinal cord injury (dorsal column lesion) The training received during this fellowship will allow me to acquire the knowledge and technical skills I need to become independent SPONSOR 19 NAMEANDDEGREE(S) Clifford J Woolf, MD, Phi) 20 POSITION/RANK Richard J K.itz Professor of Anesthesia Research 21 RESEARCHINTERESTS/AREAS Neural Regeneration / Neurobiology of Pain DESCRIPTION (Do not exceed space provided) Loss of function following injury to the central nervous system (CNS) is due to a failure of axons within the CNS to re-grow This is in contrast to the peripheral nervous system (PNS) where re-growth occurs Despite years of study, the mechanisms resgonsible for the ability of the PNS, but failure oft.he CNS to regenerate remain poorly understood Recently, advances in gene expression technology have made it possible to screen and identify thousands of gene expression profiles simultaneously using high density DNA microarrays Using this new technology, genes that appear to regulate neuronal growth have been identified, however, identification by microarrays is inadequate evidence to draw conclusions about functional significance Further characterization of these putative growth associated genes (GAGs) is therefore reqnired The aim of this study is to use the unique properties of dorsal root ganglion (DRG) neurons to validate mad characterize putative GAGs identified by microarry analysis Expression profiles of putative DRG GAGs that have the following characteristics will be examined (i) upregulated during development, (it) down regulated or not expressed in adult, (iii) upregulated after peripheral injury, and (iv) not expressed or down regulated after a central lesion The expression profiles of putative DR(; GAGs will be validated by slot, Northern, and Western blots, immunocytochemistry, and by in situ hybridization to determine cellular localization Genes that fulfill the criteria for a growth promoting GAG will be examined in vitro and in rive for their ability to regulate axonal growth and regeneration after CNS injury These restdts will increase our understanding of the reasons for failure of central regeneration and may offer novel therapeutic opportunities to treat CNS injuries PHS 416-1 (Rev 12/98) Form Page 2 BB CC Individual NRSA Application Table of Contents ========================================Section End===========================================
