Neurobiology, Plasticity, Regeneration
The goal of my research has been to understand the mechanisms that contribute to recovery after spinal cord injury and to use this knowledge to develop rational clinical treatments. Since recovery is likely to be enhanced both by rescuing damaged neurons that otherwise would have died and by permitting the regeneration of injured axons that otherwise would not have grown in the CNS, we study and seek to enhance both neuron survival and regeneration. Our emphasis now is the use of adult derived mesenchymal stem cells as transplants to augment host tissue survival and improve functional recovery following spinal cord injury. We intend to continue experiments in which we assay the effects of transplants with quantitative anatomical tracing techniques and quantitative assays of behavior. The effects of adult-derived stem cells in the repair of spinal cord injury will be particularly interesting because such cells are readily available and could be generated from the individuals own tissue, avoiding the problem of graft rejection of foreign tissue by the host. It will also be of interest to apply these techniques to chronic injury models, since the first clinical trials of transplant efficacy will likely involve spinal cord injured patients with stable deficits.
Tim Himes received his Ph.D. degree from The Medical College of Pennsylvania and his postdoctoral training in Neurobiology and Anatomy was also completed at MCP. Since finishing training, Dr. Himes has been a microbiologist at Philadelphia's Department of Veterans Affairs Medical Center and carries out this research in the Department of Neurobiology and Anatomy at Drexel University College of Medicine.
Shibayama, M., S. Hattori, B.T. Himes, M. Murray, and A. Tessler. 1998.Neurotrophin-3 (NT-3) prevents death of axotomized Clarke's nucleus neurons in adult rat. J. Comp. Neurol.390: 102-111.
Shibayama, M., N. Matsui, B.T. Himes, M. Murray, and A. Tessler. 1998.Critical interval for rescue of axotomized neurons by transplants. NeuroReport.9 (1): 1-4.
Liu, Y., B.T. Himes, J. Solowska-Baird, J. Moul, S. Chow, A. Tessler, E.Snyder, and I. Fischer. 1999. Intraspinal delivery of neurotrophin-3 (NT-3)using stem-like cells genetically modified by recombinant retrovirus. Exp.Neurol.158: 9-26.
Liu, Y., D. Kim, B.T. Himes, S.Y. Chow, H. Jin, M. Murray, A. Tessler, andI. Fischer. 1999. Transplants of fibroblasts genetically modified to express BDNF promote regeneration of adult rat rubrospinal axons. J. Neurosci. 19 (11): 4370-4387.
Sugawara, T., B.T. Himes, M. Kowada, M. Murray, A. Tessler, and W. Battisti.1999. Putative inhibitory extracellular matrix molecules do not prevent dorsal root regeneration into fetal spinal cord transplants. Neurorehab. and Neural Repair 13:135-147.
Ma, D., B.T. Himes, T.B. Shea, and I. Fischer. 2000 Axonal transport of microtubule-associated protein 1B (MAP1B) in the sciatic nerve of adult rat: distinct transport rates of different isoforms. J. Neurosci. 20:2112-2120.
Himes, B.T. and A. Tessler. 2000. Neuroprotection from cell death following axotomy. In N. Ingoglia and M. Murray (eds.) Nerve Regeneration. New York: Marcel Dekker.
Chow, S.Y., J. Moul, C.A. Tobias, B.T. Himes, Y. Liu, M. Obrocka, L. Hodge,A. Tessler, and I. Fischer 2000 Analysis of multipotential stem cells from embryonic rat spinal cord: in vitro characterization and intraspinal grafting. BrainRes. 874:87-106
Himes BT, Liu Y, Solowska JM, Fischer I, Tessler A. 2001. Transplants of cells genetically modified to express neurotrophin-3 (NT-3) rescue axotomized Clarke's nucleus neurons after spinal cord hemisection in adult rats. JNeurosci Res. 65:549-564.
Liu Y, Himes BT, Murray M. Tessler A, Fischer I. 2002. Grafts of BDNF-producing fibroblasts that promote regeneration of axotomized rubrospinal neurons also rescue most neurons from retrograde death and prevent their atrophy. Exp. Neurol. 178(2): 150-164.
Schwartz, ED, Himes, BT. 2003. New model of minimally invasive experimental spinal cord injury. Am. J. Neuroradiol. 24(2): 166-168.
Bakshi, A., O. Fisher, T. Dagci, B.T. Himes, I. Fischer and A. Lowman. 2004. Mechanically engineered hydrogel scaffolds for axonal growth and angiogenesis after transplantation in spinal cord injury. J. Neurosurg. Spine 1(3):322-329.
Neuhuber B., B.T. Himes, J.S. Shumsky, G. Gallo and I. Fischer. 2005. Axon growth and recovery of function supported by human bone marrow stromal cells in the injured spinal cord exhibit donor variations. Brain Res. 1035(1):73-85.
Swanger S.A., B. Neuhuber, B.T. Himes, A. Bakshi and I. Fischer. 2005. Analysis of allogeneic and syngeneic bone marrow stromal cell graft survival in the spinal cord. Cell Transplantation. 14(10):775-786.
Tutunculer B, G. Foffani, B.T. Himes and K.A. Moxon. 2006. Structure of the Excitatory Receptive Fields of Infragranular Forelimb Neurons in the Rat Primary Somatosensory Cortex Responding To Touch. Cerebral Cortex 16(6):791-810.
Himes B.T., G.C. Kopen, C. Coleman, R. Kushner, S. Swanger, B. Neuhuber, A. Bakshi, J.S. Shumsky, J. Wagner, and I. Fischer. 2006. Recovery of function following grafting of human bone marrow stromal cells into the injured spinal cord. Neurorehabilitation and Neural Repair. 20(2):278-296.
Kao T, J. Shumsky, S. Jacob-Vadakot, B.T. Himes, M. Murray, K. Moxon. 2006. Role of the 5-HT2C receptor for improving weight supported stepping in adult rats spinalized as neonates. Brain Res. 1112:159-168.
Park, K.I., B.T. Himes, P.E. Stieg, A. Tessler, I. Fischer and E.Y. Snyder. 2006. Neural stem cells may be uniquely suited for combined gene therapy and cell replacement: Evidence from engraftment of Neurotrophin-3-expressing stem cells in hypoxic-ischemic brain injury. Exp. Neurol. 199(1):179-190.
Solowska, J.M., Morfini, G., Falnikar, A., Himes, B.T., Brady, S.T., Huang, D. and Baas, P.W. 2008. Quantitative and functional analyses of spastin in the nervous system: implications for hereditary spastic paraplegia. J. Neurosci. 28(9):2147-2157.