New Jersey Commission on Spinal Cord Research (NJCSCR) NEW JERSEY COMMISSION ON SPINAL CORD RESEARCH (NJCSCR) This data was compiled in compliance with the New Jersey Commission on Spinal Cord Research's statutory mandate, N.J.S.A. 52:9E-1, "…to compile a directory of spinal cord research being conducted in the State." The information contained within this directory is not all-inclusive. The research projects and researchers listed in this directory are all based in the State of New Jersey, and have applied to and received funding during the fiscal year 2002 grant cycle. The research projects are not categorized, or listed in any particular order. This directory is not a complete listing of all scientific research being performed within the State of New Jersey due to the proprietary nature of the research being conducted at various institutions throughout the State. In addition, institutions are not obligated to share their research information with the New Jersey Commission on Spinal Cord Research. Please feel free to contact the New Jersey Commission on Spinal Cord Research at PO Box 360, Health & Agriculture Building, Market and Warren Streets, Trenton, New Jersey, 08625. The Commission's office can be reached by telephone at 609-292-4055, by fax at 609-943-4213, or by e-mail at For information on the New Jersey Commission on Spinal Cord Research's grant award process, grant applications, and deadlines, please see: www.state.nj.us/health/spinalcord/ 2002 MEMBERSHIP INFORMATION Susan P. Howley, Chairperson COMMISSION PERSONNEL Christine Traynor PRINCIPAL INVESTIGATOR - CRISTA L. ADAMSON, Ph.D. Project Title - Vaccination Therapies of Rat Spinal Cord Injury This application explores a newly discovered approach to promote regeneration of the spinal cord and restoration of function after spinal cord injury by activating selected immune function through immunization using spinal cord homogenates, myelin basic protein, and glatiramer acetate as antigens. This is a timely project addressing a promising therapeutic measure. Recent studies suggest that humeral and cellular immunity play a major role in spinal cord injury, but these studies have left several gaps that must be filled before therapies can be taken to clinical trial for chronic spinal cord injury. The Principal Investigator will be utilizing a well-characterized and standardized rat spinal cord contusion model, and will investigate the effects of spinal cord homogenates (SCH), myelin basic protein (MBP), glatiramer acetate (Copaxone CPX), and incomplete Freund's adjuvant controls (IFA) vaccination of rats, before, shortly after, and six weeks after injury. The rat spinal cord contusion model has many advantages over other models, as it produces very consistent injuries that are very similar to human spinal cord injury. Well-defined behavioral measures are available for the model. Contusions eliminate the corticospinal tract (CST) located close to the center of the cord, and this is useful for assessing regeneration of at least one important descending motor tract. Thus, it is an appropriate choice for a model to confirm and extend the findings from other recent studies that have been completed. The proposal's experiments will confirm or refute the hypotheses that SCH, MBP, and CPX vaccinations promote regeneration and locomotor recovery in a well-standardized rat spinal cord contusion model. They should also be able to determine the respective roles of humeral and cellular immune responses to these vaccines. This data will help move these potential exciting therapies closer to clinical trial. Contact Information: PRINCIPAL INVESTIGATOR - GAIL FORREST, Ph.D. Project Title - Effect of Body Weight Supported Walking in Incomplete SCI: Physiological and Performance Effects This proposal addresses two major problems of spinal cord injury subjects, mobility and cardiovascular autonomic function. This proposal will evaluate independent walking after incomplete spinal cord injury through body weight support treadmill training. Although the primary purpose of rehabilitation is to regain walking, many individuals with spinal cord injury do not regain the ability to walk. Any walking improvements are limited by insufficient muscle activity to promote stepping, maintain balance and cope with weight bearing problems. Typically, traditional rehabilitation includes stretching, strengthening and functional gait with assistive devices; however, gait performance plateaus and is followed by minimal improvements. Recently researchers have suggested and demonstrated that a preferred alternative to traditional rehabilitation is treadmill training where the body is supported by an overhead harness attached to the trunk. Treadmill training with body weight support has the potential to restore walking independence. The suggestion is that the spinal cord can perform on its own without input from the brain. Research suggests that the spinal cord neuronal circuits may "learn" or be retrained by rhythmic loading and unloading of limbs during locomotion with body weight support while walking on a treadmill. The ultimate goal is to allow the individual to walk overground with increased walking velocity and coordination. The main aim of this study is to investigate the effectiveness of progressive treadmill training with body weight support while treadmill walking for incomplete spinal cord injury compared to a traditional training rehabilitation intervention. The Principal Investigator will also investigate how training can lead to independent overground walking. This study may validate previous research findings regarding the efficacy of the training method. Replication of these studies is immensely important. Contact Information: PRINCIPAL INVESTIGATOR - WILMA J. FRIEDMAN, Ph.D. Project Title - p75 - Medicated Cell Death After Spinal Cord Injury This proposal seeks to determine whether the p75 receptor mediates cell death after spinal cord injury. This proposal explores an interesting concept that progressive cell loss after spinal cord injury may be mediated by a p75 receptor mechanism. It proposes to determine the relative role of p75 mediated cell death in the absence of signaling via the Trk receptors in inducing neuronal cell death. Following spinal cord injury there is a local induction of numerous cytokines and growth factors due to the inflammatory response to the damage. Many of these growth factors that are induced following injury may be beneficial and assist in recovery of function, however, some of these factors may have detrimental effects and exacerbate cell loss. Neutrophins, specifically nerve growth factor (NGF), are induced in a variety of cell types following injury. Although NGF is well known to support neuron survival acting via the Trk tyrosine kinase receptors, recent studies have demonstrated that NGF can also act via a distinct receptor, p75 to induce cell death. This proposal will investigate whether p75 mediates a similar signal for neurons to die in the spinal cord after damage, as it does in the brain. Results derived from the proposed studies may lead to the discovery of an important mechanism of delayed cell death after spinal cord injury and lead to novel therapeutic strategies to prevent progressive degeneration by blocking the p75 receptor mechanism, or its downstream signaling processes. Contact Information: PRINCIPAL INVESTIGATOR - MARTIN GRUMET, Ph.D. Project Title - Analysis of Cytotoxic Activity Following Spinal Cord Injury This proposal will analyze why cells die following injury, and find ways to improve survival of transplanted cells. This proposal addresses one of the most important elements responsible for the progressive destruction of spinal cord tissue following an initial injury, the local production or accumulation of cytotoxic factors in the damaged cord. Following traumatic spinal cord injury, there is a short period in which neurons (nerve cells) die and a much longer period during which glial cells (the major cells in the brain that are not nerve cells) die. Understanding what causes these cells to die is of great importance for the design and testing of new therapies to improve recovery following injury to the central nervous system. However, little is known about molecular mechanisms that underlie the death of cells in the spinal cord following injury. Therefore, there is a need for in vitro models to study molecules responsible for cell death. By the utilization of a test to measure cell killing activity that is present in extracts of contused, but not normal spinal cord, the intent is to analyze the nature of the cell killing activity. Testing will determine quantitatively how much activity is generated and how long it persists following traumatic spinal cord injury. A glioma cell line will be used to pilot the test as well as neurons, and glia (astrocytes and oligodendrocytes). The sensitivity of neural stem cells (which can give rise to nerve cells) will be evaluated for transplantation to promote nerve regeneration. Parallel studies will be performed to analyze the survival of stem cells transplanted into the spinal cord at various times following contusive injury. The second aim of this proposal is to determine the biochemical nature of cytotoxic activity. Treatments that disrupt proteins, as well as gene chip analysis, will be performed to identify groups of genes that correlate with acute and extended periods of death of neurons and glia, respectively. This combined approach will focus on those molecules that play critical roles in cytotoxicity. Contact Information: PRINCIPAL INVESTIGATOR - RONALD P. HART, Ph.D. Project Title - Sharing and Mining SCI Microarray Data Aim of the proposal is to provide microarray analysis and data mining services for spinal cord researchers. The ability to carry out, analyze and interpret DNA microarray experiments is unarguably important in addressing a large number of questions related to spinal cord injury and repair. This proposal extends an existing infrastructure for microarray production and services, including a microarray database with web-based access for spinal cord injury investigators. Microarrays combine the successes of human genome projects with traditional biochemical research. This technology allows researchers to examine the effects of injury, drugs or transplant therapies on huge numbers of gene responses, so that unexpected results can be identified. The data will be entered in a standard format together with details of the spinal cord injury and outcome. Computerized data-mining techniques will be employed in an attempt to discern patterns of expression that might correlate with improved or poor outcomes. The ability to provide high-quality microarrays in adequate numbers and at a reasonable cost would be a very valuable contribution in itself. Development and maintenance of a widely accessible database compliant with evolving norms for microarray databasing and analysis would be a further substantial contribution. The proposal's development of an infrastructure to support collaborative and interdisciplinary research on spinal cord injuries would support relevant research and would be an important innovation in the field. Contact Information: PRINCIPAL INVESTIGATOR - MICHAEL P. MATISE, Ph.D. Project Title - Cell-Cycle Regulators Controlling Proliferation and Differentiation of Spinal Neurons This proposal will provide basic information regarding the developmental mechanisms that control spinal cord formation. This information is important for advancing toward stem cell based therapies. These studies are concerned with studying the role of proteins that regulate the exit of spinal interneurons from the cell cycle, and thus control differentiation. The proposal's aim is to elucidate the molecular genetic pathways that control proliferation and differentiation on spinal cord interneurons in order to determine their potential as therapeutic targets in treating spinal cord injury. Severe traumatic injury to the spinal cord is often accompanied by widespread degeneration of neurons. Current approaches to restoring function following such injuries involve either replacement therapies (transplantation of various types of immature "stem cells"), or encouragement of spared cell populations to divide and/or sprout new connections. In either case, these strategies rely on the ability of spared neurons or transplanted cells to regenerate, as much as possible, the cellular and synaptic complexity that was established during embryogenesis. Successful therapies thus depend to a large extent on accurately re-capitulating events that occur only during embryogenesis, since adult neurons do not divide or rewire their connections on a large scale. Therefore, a thorough understanding of the mechanisms that control neuronal cell proliferation and differentiation in immature neurons during spinal cord development is a prerequisite to therapeutic strategies that seek to attenuate or reverse the affects of spinal cord injury. The experiments in this proposal are designed to address these issues by focusing on the role of an important class of cell cycle regulator in neural differentiation during spinal cord development. The Principal Investigator will employ both standard techniques using mice as the model system, as well as developing a novel method for introducing DNA into cultured mammalian cells for the purposes of manipulating their ability to divide and mature. The knowledge gained from these studies will form an important foundation for the design of therapies to treat human patients with spinal cord injury. Contact Information: PRINCIPAL INVESTIGATOR - JAMES H. MILLONIG, Ph.D. Project Title - Vacuolated Lens (vl) a Mouse Model for Spinal Cord Regeneration The goal of this proposal is to identify mechanisms that produce neuronal growth in the adult central nervous system. Understanding the molecular nature of this mutation may lead to methods to promote and enhance the survival and proliferation of such cells in the spinal cord. Alternatively, it may lead to methods to generate spinal neurons from stem cells destined for transplant to an injured cord. The ultimate goal of spinal cord regeneration research is to restore motor and sensory function in individuals that have lost these capabilities due to disease or injury. This theoretically can be accomplished by using stem cells. The stem cells would be introduced into the adult spinal cord so that new neurons can be incorporated into functional circuits. For this to work, however, the stem cells must be instructed to a spinal cord fate. Thus, the signals that control this process during embryogenesis need to be elucidated. For this reason, the study of spinal cord development is important for the future success of stem cell mediated regeneration research. The Principal Investigator's laboratory studies naturally occurring mouse mutations as a means of understanding spinal cord development, recent research has focused on a spontaneous mouse mutation called vacuolated lens (vl). It was discovered that dorsal sensory and ventral motor neurons are overproduced in mutant embryos. The goal of this proposal is to determine the cellular and molecular causes of this phenotype so that stem cells restricted to a spinal cord lineage can be overproduced as a novel regeneration therapy. Contact Information: PRINCIPAL INVESTIGATOR - RICHARD S. NOWAKOWSKI, Ph.D. Project Title - Cell Proliferation in the CNS after Spinal Cord Injury This proposal seeks to characterize the dynamics of cell division after lateral hemi-section-induced spinal cord injury in a much more rigorous way than has been carried out thus far in the literature. The Principal Investigator will describe the location and time course of cell proliferation, and characterize the cell types generated at different times and locations in accordance with this information. The information gained from these studies may provide insight into the cellular basis of inflammation and glial scar formation after spinal cord injury, and provide a better understanding of injury parameters that may affect the design of clinical therapeutics. Cell proliferation will be characterized rigorously after an experimental injury to the spinal cord. After traumatic injury to the spinal cord, the cells in the vicinity of the injury respond by proliferating. This proliferative response in the central nervous system (CNS) is different from the proliferative response found in other tissues such as skin because it does not directly contribute to healing. In addition, because neurons have axons that interconnect distant parts of the CNS, the proliferative reaction to an injury is not necessarily confined to the immediate vicinity of the injury. The goal of this project is to characterize rigorously and precisely where and when cell proliferation occurs in the CNS after an injury to the spinal cord and what kinds of CNS cells are involved in the proliferative response. This project is significant because a specific catalog of the sites and time course of the cell proliferation and cell types involved that occur after a spinal cord injury is not available. This information will be useful to understand how the "scar" that forms after CNS injury forms, and why CNS regeneration is generally not successful. In addition, knowledge of when and where cell proliferation occurs is necessary base knowledge for certain types of therapies that will use retroviruses as a delivery mechanism for genetic engineering that may facilitate recovery of function after a spinal cord injury. Contact Information: |
