Leif A. Havton, M.D., Ph.D.

Professor

Department of Neurology

David Geffen School of Medicine at UCLA

Dr. Havton’s current position is as Professor in the Department of Neurology at the David Geffen School of Medicine at UCLA. He is a clinical neurologist and basic neuroscientist. Dr. Havton graduated from Umea University School of Medicine, Sweden, with an MD in 1988 and a PhD in Anatomy in 1989. His PhD thesis described new forms of regenerative synaptogenesis by supernumerary axons in motoneurons and plasticity of spinal cord reflexes after a peripheral nerve injury. Dr. Havton completed postdoctoral research training at UCSF in San Francisco, CA and performed comparative studies on the morpho-physiology of the somatosensory thalamus in rodent and large mammalian models. He completed an internship in internal medicine at St. Mary’s Hospital and Medical Center in San Francisco, CA, in 1992 and residency training in neurology at Stanford University Medical Center in 1995. Dr. Havton stayed on as clinical faculty at a Stanford University Teaching Hospital between from 1995 to 2000. He joined the faculty of the Department of Neurology at UCLA in 2000. Between 2010 and 2015, Dr. Havton was on the faculty at UC Irvine anda member of the UC Irvine Stem Cell Research Center and the Reeve-Irvine Spinal Cord Injury Research Center. In 2015, Dr. Havton returned to the Department of Neurology at UCLA. His research lab studies spinal cord injury in basic and translational research models with a special interest in the repair of cauda equina and conus medullaris forms of spinal cord injury.

Research Description and Approach

The Havton laboratory studies neural repair of autonomic, motor, and sensory functions after spinal cord injury. The laboratory has a special interest in studies of the lumbosacral portion of the spinal cord its associated nerve roots, the cauda equina. The studies are translational and include multiple outcome measures to assess, for instance, autonomic function, somatosensory and visceral pain, and locomotion. The Havton laboratory also collaborates extensively with multiple laboratories in excellent academic institutions across North America and Europe.

The Havton laboratory uses a multi-disciplinary approach for studies at the systems, cellular, and molecular levels. Research strategies include behavioral assessments, electrophysiological techniques, gene expression studies, immunohistochemistry, and anatomical tract tracing at both the light and electron microscopic levels. The studies are translational and aim at finding novel approaches to ultimately improve neurological function after spinal cord and nerve root injury.

The Havton laboratory has received funding from multiple federal, state, and foundation sources. Current research support includes grants from the National Institutes of Health, the Department of Defense Spinal Cord Injury Research Program, the Veterans Affairs, the California Institute for Regenerative Medicine, and the Dr. Miriam and Sheldon G. Adelson Medical Research Foundation.

Selected/Recent Publications

– Chang HH, Havton LA. Serotonergic 5-HT(1A) receptor agonist (8-OH-DPAT) ameliorates impaired micturition reflexes in a chronic ventral root avulsion model of incomplete cauda equina/conus medullaris injury. Exp Neurol. 2013 Jan;239:210-7. doi: 10.1016/j.expneurol.2012.10.015. Epub 2012 Oct 23.

– Carlstedt T, Havton L. The longitudinal spinal cord injury: Lessons from intraspinal plexus, cauda equina and medullary conus lesions. Handb Clin Neurol. 2012;109:337-54.

– Lu P, Wang Y, Graham L, McHale K, Gao M, Wu D, Brock J, Blesch A, Rosenzweig ES, Havton LA, Zheng B, Conner JM, Marsala M, Tuszynski MH. Long-distance growth and connectivity of neural stem cells after severe spinal cord injury. Cell. 2012 Sep 14;150(6):1264-73.

– Lu P, Blesch A, Graham L, Wang Y, Samara R, Banos K, Haringer V, Havton L,Weishaupt N, Bennett D, Fouad K, Tuszynski MH.
Motor axonal regeneration after partial and complete spinal cord transection. J Neurosci. 2012 Jun 13;32(24):8208-18.

– Chang HH, Havton LA. Modulation of the visceromotor reflex by a lumbosacral ventral root avulsion injury and repair in rats. Am J Physiol Renal Physiol. 2012 Sep;303(5):F641-7.

– Havton LA. A lumbosacral ventral root avulsion injury and repair model for studies of neuropathic pain in rats. Methods Mol Biol. 2012;851:185-93.

– Wu L, Wu J, Chang HH, Havton LA. Selective plasticity of primary afferent innervation to the dorsal horn and autonomic nuclei following lumbosacral ventral root avulsion and reimplantation in long term studies. Exp Neurol. 2012 Feb;233(2):758-66. Epub 2011 Dec 8.

– Chang HH, Havton LA. Systemic administration of fluorogold for anatomical pre-labeling of autonomic and motor neurons in the rat spinal cord compromises urodynamic recordings in acute but not long-term studies. Neurourol Urodyn. 2012 Jan;31(1):162-7. doi: 10.1002/nau.21184. Epub 2011 Aug 8.

– Zai L, Ferrari C, Dice C, Subbaiah S, Havton LA, Coppola G, Geschwind D, Irwin N, Huebner E, Strittmatter SM, Benowitz LI.
Inosine augments the effects of a Nogo receptor blocker and of environmental enrichment to restore skilled forelimb use after stroke. J Neurosci. 2011 Apr 20;31(16):5977-88.

– Ichiyama RM, Broman J, Roy RR, Zhong H, Edgerton VR, Havton LA. Locomotor training maintains normal inhibitory influence on both alpha- and gamma-motoneurons after neonatal spinal cord transection. J Neurosci. 2011 Jan 5;31(1):26-33.

Source: University of California, Irvine (http://www.anatomy.uci.edu/havton.html)

Dr.François Giuliano, M.D, Ph.D. Department of Physical Medicine and Rehabilitation, Raymond Poincaré Hospital, Garches, France.

François Giuliano, MD, PhD, certified in urology, is Professor of Therapeutics at the Versailles Saint Quentin en Yvelines – University, and has a specialised urological practice in the Department of Physical Medicine and Rehabilitation at the Raymond Poincaré Academic Hospital of Garches, France. His practice focuses on non-malignant diseases of the bladder and prostate and on sexual medicine, especially associated with neurological diseases.

FG’s major research interests include the pathophysiology, diagnosis and management of lower urinary tract and sexual dysfunction especially when caused by neurological conditions. He has an extensive experience conducting clinical trials and is a recognized authority on the study of male functional urology and sexual medicine.

He runs an active research laboratory which investigates the physiological and pharmacological mechanisms controlling sexual and lower urinary tract functions, with a particular interest in the neural control. He is a widely published author in peer-reviewed journals (over 250 original papers and review articles), and has edited and contributed to several books. He has won several national and international awards.

His research group has designed preclinical models to investigate the pathophysiology of neurogenic detrusor overactivity especially after spinal cord injury since 10 years. FG’s group has a widely recognized expertise in the preclinical investigation of innovative treatment for neurogenic detrusor overactivity. As a recognition of this expertise, FG has partnered with many pharmaceutical companies to perform proof of concept studies in this field.

FG participated in the clinical development of numerous compounds for male sexual dysfunction and lower urinary tract symptoms, and especially those he had investigated pre-clinically.  He was involved as principal investigator in numerous phase II and phase III clinical trials. In particular, he led the three main international clinical trials for erectile dysfunction in spinal cord injured patients.

FG is the current president-elect of the European Society for Sexual Medicine and the deputy director of the of the Inserm Unit 1179, leading the team Biotherapy & Pharmacology of Neurogenic Uro-Genito-Sexual Dysfunctions.

Distinguished Professor, Department of Neurobiology,

Distinguished Professor, Department of Integrative Biology and Physiology

Distinguished Professor, Department of Neurosurgery

Member, Brain Research Institute University of California, Los Angeles

 

Professional Degrees

1962    B.S., Biology and Physical Education, East Carolina University

1963    M.S., Physical Education, University of Iowa

1968    Ph.D., Exercise Physiology, Michigan State University

 

Educational Appointments and Professional Experience

2012-present      Distinguished Professor, Department Neurosurgery, UCLA

2010-present      Distinguished Professor, Department Integrative Biology & Physiology, UCLA

2002-2003          Acting Director of the Brain Research Institute, University of California, Los Angeles

1999-present      Distinguished Professor, Department of Neurobiology, UCLA

1999-2010          Distinguished Professor, Department of Physiological Science, UCLA

1996-2001          Vice Chair, Department of Physiological Science, UCLA

1989-1999          Professor, Department of Physiological Science, UCLA

1985-1989          Professor and Chair, Department of Kinesiology, UCLA

1976-1989          Professor, Department of Kinesiology, UCLA

1972-1976          Associate Professor, Dept. of Kinesiology, UCLA

1968-1971          Assistant Professor, Department of Kinesiology, UCLA

 

Honors and Awards (Past 10 years)

2014                  Step-By-Step Foundation Award

2014                  ACRM John Stanley Coulter Lecture Award

2013                  Magoun Distinguished Lecture: Outstanding Achievement by BRI Member

2013                  Experimental Biology: Environmental and Exercise Honor Award

2012                   J. Allyn Taylor International Prize in Medicine – Spinal Cord Injury

2011                   Popular Mechanics Breakthrough Award

2009-2011          National Academy of Sciences: Decadal Survey: Animal and Human Biology Panel

2008                   President’s Lecture at the American College of Sports Medicine,

2004                   Edward F. Adolph Distinguished Lecturer of the American Physiological Society,Environmental and Exercise Physiology Section

 

Papers Published (Past 5 years, over 460 total)

1. Tillakaratne, N.J.K., Guu, J.J., de Leon, R.D., Bigbee, A.J., London, N.J., Zhong, H., Ziegler, M.D., Joynes, R.L., Roy, R.R., and Edgerton, V.R. Functional recovery of stepping in rats after a complete neonatal spinal cord transection is not due to re-growth across the lesion site. Neuroscience 166:23-33, Mar 2010, PMC2820384.
2. Edgerton VR, Roy RR. Spasticity: a switch from inhibition to excitation. Nat Med. 2010 Mar;16(3):270-1.
3. Gerasimenko, Y., Gorodnichev, R., Machueva, E., Pivovarova, E., Semyenov, D., Savochin, A., Roy, R.R., and Edgerton, V.R. Novel and direct access to the human locomotor spinal J. Neuroscience 30(10): 3700-3708 March 2010 PMC2847395
4. Chi, SW., Hodgson, J., Chen, JS., Edgerton, V.R., Shin, DD., Roiz, RA., and Sinha, S. Finite Element Modeling Reveals Complex Strain Mechanics in the Aponeuroses of Contracting Skeletal Muscle. J Biomech. 43:1243-1250 2010 PMC2857665
5. Kim, J.A., Roy, R.R., Kim, S.J., Zhong, H., Haddad, F., Baldwin, K.M. and Edgerton, V.R. Electromechanical modulation of catabolic and anabolic pathways in chronically inactive, but neurally intact, muscle. Muscle Nerve 42(3):410-21 2010 PMC2950751
6. Dy, C., Gerasimenko, Y., Edgerton, V.R., Dyhre-Poulsen, P., Courtine, G., and Harkema, S. Phase dependent modulation of percutaneously elicited multisegmental muscle responses after spinal cord injury. Neurosci. 103(5): 2808-20 May 2010 PMC2867577
7. Brock, J., Rosenzweig, E., Blesch, A., Moseanko, R., Havton, L., Edgerton, V.R., and Tusynski, M. Local and remote growth factor effects after primate spinal cord injury. Neurosci 2010 30(29):9728-37 2010 PMC2927098
8. Ziegler, M.D., Zhong, H, Roy, R.R., and Edgerton, V.R. Why variability facilitates spinal learning. Neurosci 30: 10720-10726. 2010 PMC3046122
9. Kinugasa, R., Hodgson, J.A., Edgerton, V.R., Shin, D.D., and Sinha, S. Reduction in tendon elasticity from unloading is unrelated to its hypertrophy. J Appl Physiol 109(3):870-7, 2010. PMC2944640
10. Lee, Y.S., Zdunowski, S., Edgerton, V.R., Roy, R.R., Zhong, H., Hsiao, I, and Lin, V.W. Improvement of gait patterns in step-trained, complete spinal cord-transected rats treated with a peripheral nerve graft and acidic fibroblast growth factor. Exp Neurol 224(4):429-37, 2010. PMC3036744
11. Rosenzweig, E.S., Courtine, G., Jindrich, D., Brock, J.H., Strand, S., Ferguson, A.R., Nout, Y., Roy, R.R., Miller, D., Beattie, Havton, L.A., Bresnahan, J., Edgerton, V.R., and Tuszynski, M.H. Extensive spontaneous plasticity of corticospinal projections after primate spinal cord injury. Nature Neurosci. 13:1505-1510, 2010. PMC3144760.
12. Joseph, M.J., Bilousova, T., Zdunowski, S., Wu, Z.P., Middleton, B., Boudzinskaia, M., Wong, B., Ali, N., Zhong, H., Yong, J., Washburn, L., Escande-Beillard, N., Dang, H., Edgerton, V.R., Tillakaratne, N., and Kaufman, D. Transgenic mice with enhanced neuronal major histocompatibility complex class I expression recover locomotor function better after spinal cord injury. Neurosci. 89:365-372. 2011. PMC3087178
13. Roy, R.R., Zhong, H., Monti, R.J., Kim, J.A. and Edgerton, V.R. Selectively reshaping a skeletal muscle phenotype: functional overload of cat plantaris. Muscle Nerve. 43(4):489-99. 2011. PMC3058689
14. Ichiyama, R.M., Broman, J., Roy, R.R., Zhong, H., Edgerton, V.R. and Havton, L.A. Locomotor training maintains normal inhibitory influence on motoneurons after spinal cord injury. Neurosci. 31(1):26-33. 2011. PMC3036743.
15. Jindrich, D.L., Courtine, G., Liu, J.J., McKay, H.L., Moseanko, R., Bernot, T.J., Roy, R.R., Zhong, H., Tuszynski, M.H., and Edgerton, V.R. Unconstrained three-dimensional reaching in Rhesus monkeys. Brain Res. 209(1):35-50. 2011. PMC3035773.
16. Johnson, W.L., Jindrich, D.L., Zong, H., Roy, R.R., and Edgerton, V.R. Application of a rat hindlimb model: a prediction of force spaces reachable through stimulation of nerve fascicles. IEEE Trans Biomed Eng.  IN PRESS PMC3090502
17. Ziegler, Matthias D., Hsu, D., Takeoka, A., Zhong, H., Almudena, R.C., Phelps, P.E., Roy, R.R., and Edgerton, V.R. Further evidence of olfactory bulb ensheathing glia facilitating functional axonal regeneration after a complete spinal cord transection. Exp Neuro. 229(1): 109-19. 2011. PMC3085566
18. Harkema, Susan J., Schmidt-Read, M., Lorenz, D., Edgerton, V.R., and Behrman, A.L. Balance and ambulation improvements in individuals with chronic incomplete spinal cord injury using locomotor training-based rehabilitation. Arch Phys Med Rehabil. 2011 Jul 19.
19. Harkema, Susan J., Schmidt-Read, M., Behrman, A.L., Bratta, A., Sisto, S.A., and Edgerton, V.R. Establishing the neurorecovery network: multisite rehabilitation centers that provide activity-based therapies and assessments for neurologic disorders. Arch Phys Med Rehabil. 2011 Jul 19.
20. Harkema, S.J., Schmidt-Read, M., Lorenz, D., Edgerton, V.R., and Behrman, A.L. Balance and ambulation improvements in individuals with chronic incomplete spinal cord injury using locomotor training-based rehabilitation. 93(9):1508-1. Arch Phys Med Rehabil. 2011 Jul 19.
21. Harkema, S.J., Schmidt-Read, M., Behrman, A.L., Bratta, A., Sisto, S.A., and Edgerton, V.R. Establishing the neurorecovery network: multisite rehabilitation centers that provide activity-based therapies and assessments for neurologic disorders. 93(9):1498-507. Arch Phys Med Rehabil. 2011 Jul 20.
22. Edgerton, V.R., and Harkema, S. Epidural stimulation of the spinal cord in spinal cord injury: current status and future challenges. Expert Rev Neurother. 11:1351-3, 2011. PMC3361963.
23. Takeoka, A., Jindrich, D.L., Muñoz-Quiles, C., Zhong, H., van den Brand, R., Pham, D.L., Ziegler, M.D., Ramón-Cueto, A., Roy, R.R., Edgerton, V.R., and Phelps, P.E. Axon regeneration can facilitate or suppress hindlimb function after olfactory ensheathing glia
    J Neurosci. 31:4298-310, 2011. PMC3327612
24. Johnson, W.L., Jindrich, D.L., Zong, H., Roy, R.R., and Edgerton, V.R. Application of a rat hindlimb model: a prediction of force spaces reachable through stimulation of nerve fascicles. IEEE Trans Biomed Eng. 58:3328-38, 2011. PMC3090502
25. Shah, P.K., Song, J., Kim, S., Zhong, H., Roy, R.R., and Edgerton, V.R. Rodent estrous cycle response to incomplete spinal cord injury, surgical interventions, and locomotor training. Behav Neurosci.125:996-1002, 2011. PMC3361964.
26. Nandra, M.S., Lavrov, I.A., Edgerton, V.R, and Tai, Y.C. A parylene-based microelectrode array implant for spinal cord stimulation in rats. Conf Proc IEEE Eng Med Biol Soc. 23:1007-1010, 2011. PMC3154740
27. Nagatomo, F., Roy, R.R., Takahashi, H., Edgerton, V.R., and Ishihara, A. Effect of exposure to hyperbaric oxygen on diabetes-induced cataracts in mice. J Diabetes. 3:301-8, 2011.
28. Musienko, P., van den Brand, R., Märzendorfer, O., Roy, R.R., Gerasimenko, Y., Edgerton, V.R., and Courtine, G. Controlling specific locomotor behaviors through multidimensional monoaminergic modulation of spinal circuitries. J Neurosci 31:9264-78, 2011. PMCID:PMC3422212
29. Kinugasa, R., Hodgson, J.A., Edgerton, V.R., and Sinha, S. Asymmetric deformation of contracting human gastrocnemius muscle. J Appl Physiol. 112:463-470, 2012. PMCID:PMC3289422
30. Gorodnichev, R.M., Pivovarova, E.A., Puhov, A., Moiseev, S.A., Savochin, A.A., Moshonkina, T.R., Chsherbakova, N.A., Kilimnik, V.A., Selionov, V.A., Kozlowskaya, I.B., Edgerton, V.R., and Gerasimenko, Y.P. Transcutaneous electrical stimulation of the spinal cord: A noninvasive tool for the activation of stepping pattern generators in humans. Human Physiol 38:158-167, 2012.
31. Musienko, P., Courtine, G., Tibbs, J.E., Kilimnik, V., Savochin, A., Garfinkel, A.,  Roy, R.R., Edgerton, V.R., and Gerasimenko, Y. Somatosensory control of balance during locomotion in decerebrated cat. J Neurophysiol. 107:2072-2082, 2012.
32. Gad, P., Woodbridge, J., Lavrov, I., Zhong, H., Roy, R.R., Sarrafzadeh, M., and Edgerton, V.R. Forelimb EMG-based trigger to control an electronic spinal bridge to enable hindlimb stepping after a complete spinal cord lesion in rats. 9(1):38. J Neuro Eng Rehab. 2012 June 12.
33. Edgerton, V.R. and Roy, R.R. A new age for rehabilitation. Eur J Phys Rehabil Med. 48:99-109. 2012 Mar 12
34. Johnson, W.L., Jindrich, D.L., Roy, R.R., and Edgerton, V.R. Quantitative metrics of spinal cord injury recovery in the rat using motion capture electromyography and ground reaction force measurement. J Neurosci Methods 206:65-72, 2012.
35. Sinha, S., Shin, D.D., Hodgson, J.A., Kinugasa, R., and Edgerton V.R. Computer-controlled, MR-compatible foot-pedal device to study dynamics of the muscle tendon complex under isometric, concentric, and eccentric contractions. J Magn Reson Imaging. 36:498-50.4 2012 Mar 5.
36. Nout, Y.S., Rosenzweig, E.S., Brock, J.H., Strand, S.C., Moseanko, R., Hawbecker, S., Zdunowski, S., Nielson, J.L., Roy, R.R., Courtine, G., Ferguson, A.R.,Edgerton, V.R., Beattie, M.S., Bresnahan, J.C., and Tuszynski, M.H. Animal models of neurologic disorders: A honhuman primate model of spinal cord injury. 9:380-92. 2012 Mar. 17. PMC3337011
37. Nout, Y.S., Ferguson, A.R., Strand, S.C., Moseanko, R., Hawbecker, S., Zdunowski, S., Nielson, J.L., Roy, R.R., Zhong, H., Rosenzweig, E.S., Brock, J.H., Courtine, G.,Edgerton, V.R., Tuszynski, M.H., Beattie, M.S., and Bresnahan, J.C. Methods for functional assessment after C7 spinal cord hemisection in the Rhesus monkey. Neurorehabil Neural Repair. 26:556-69. 2012 Feb 13. PMC3468651
38. Shah, P., Gerasmenko, Y., Shyu, A., Zhong, H., Roy, R.R., and Edgerton, V.R. Variability in step training enhances locomotor recovery after a spinal cord injury. Eur J Neurosci. 36:2054-62. 2012 May 16. PMC3389255
39. Hodgson, J.A., Chi, S.W., Yang, J.P., Chen, J.S.,Edgerton, V.R., and Sinha, S. Finite element modeling of passive material influence on the deformation and force output of skeletal muscle. J Mech Behav Biomed Mater. 9:163-83, 2012.
40. Roy, R.R., and Edgerton, V.R. Neurobiological perspective of spasticity as occurs after a spinal cord injury. Experimental Neurology. 235: 116–122, 2012.
41. Zhong, Roy, R.R., Nakada K.K., Zdunowski, S., Khalili, N., de Leon R.D., and Edgerton, V.R. Accomodation of the spinal cat to a tripping perturbation. Frontiers in Physiology. 3: 1-10, 2012. PMC3340914
42. Harkema, S.J., Schmidt-Read, M., Lorenz, D., Edgerton, V.R., Behrman, A.L. The authors respond: balance and ambulation improvements in individuals with chronic incomplete spinal cord injury using locomotor training-based rehabilitation. Archives of Physical Medicine and Rehabilitation. 93: 919-921, 2012.
43. Harkeman, S.J., Schmidt-Read, M., Lorenz, D.J., Edgerton, V.R., and Behrman, A.L.. Balance and Ambulation Improvements in Individuals With Chronic Incomplete Spinal Cord Injury Using Locomotor Training–Based Rehabilitation. Arch Phys Med Rehabil 93 (9): 1508-1517, 2012.
44. Harkeman, S.J., Schmidt-Read, M., Behrman, A.L., Bratta, A., Sisto, S.A., and Edgerton, V.R. Establishing the NeuroRecovery Network: Multisite Rehabilitation Centers That Provide Activity-Based Therapies and Assessments for Neurologic Disorders. Arch Phys Med Rehabil 93 (9): 1498-1507, 2012.
45. Roy, R.R., Harkeman, S.J., and Edgerton, V.R. Basic Concepts of Activity-Based Interventions for Improved Recovery of Motor Function After Spinal Cord Injury. Arch Phys Med Rehabil 93 (9): 1487-1497, 2012.
46. Joseph, M.S., Ying, Z., Zhuang, Y., Zhong, H., Wu, A., Bhatia, H.S., Cruz, R., Tillakaratne, N.J., Roy, R.R., Edgerton, V.R., and Gomez-Pinilla, F. Effects of diet and/or exercise in enhancing spinal cord sensorimotor learning. PLos One 7:e41288, 2012. PMC3401098
47. Gad, P., Choe, J., Zhong, H., Roy, R.R., Tai, Y. C., Edgerton, V.R. Development of a multi-electrode array for spinal cord epidural stimulation to facilitate stepping and standing after a complete spinal cord injury in adult rats. J Neuroeng Rehabil 10(1):2, 2013. PMC3599040
48. Gad P, Lavrov IA, Shah P, Zhong H, Roy RR, Edgerton VR, Gerasimenko Y. Neuromodulation of motor-evoked potentials during stepping in spinal rats. J Neurophysiol. 2013 Jun 12.
49. Csapo R, Hodgson JA, Kinugasa R, Edgerton VR, Sinha S. Ankle morphology amplifies calcaneus movement relative to triceps surae muscle shortening. J Appl Physiol. 115(4): 468-473, 2013. PMC 3742942
50. Musienko, P.E., Gorskii, O.V., Kilimnik, V.A., Kozloviskaia, I.B., Courtine, G., Edgerton, V.R., and Gerasimenko, I.P. Neuronal control of posture andlocomotion in decerebrated and spinalized animals. Ross Fiziol Zh Im I M Sechenova. 99(3): 392-405, 2013.
51. Shah, P.K., Garcia-Alias, G., Choe, , Gad, P., Gerasimenko, Y., Tillakaratne, N., Zhong, H., Roy, R.R., and Edgerton, V.R. Use of quadrupedal step training to re-engage spinal interneuronal networks and improve locomotor function after spinal cord injury. Brain. 136(Pt:11)3362-3377. 2013. PMC3808689
52. Baldwin, K.M., Haddad, F., Pandorf, C.E., Roy, R.R., and Edgerton, V.R. Alterations in muscle mass and contractile phenotype in response to unloading models: role of transcriptional/pretranslational mechanisms. Front Physiol. 4:284. doi: 10.3389/fphys.2013.00284
53. Gad, P., Choe, J., Shah, P., Alias, G.G., Rath, M., Gerasimenko, Y., Zhong, H., Roy, R.R., and Edgerton, V.R. Sub-threshold spinal cord stimulation facilitates spontaneous motor activity in spinal rats. Neuroeng Rehabil. 10:108 doi:10.1186/1743-0003-10-108, 2013.
54. Sayenko, D.G., Angeli, C.A., Harkema, S.J., Edgerton, V.R., and Gerasimenko, Y.P. Neuromodulation of evoked muscle potentials induced by epidural spinal cord stimulation in paralyzed individuals. Neurophysiol. 111:1088-1099, 2014.
55. Kinugasa, R., Oda, T., Komatsu, T., Edgerton, V.R., Sinha, S. Interneurosis shear strain modulates behavior of myotendinous junction of the human triceps surae. Physiol Rep., 2013, 1no. e00147DOI: 10.1002/phy2.147
56. Curzi, D., Lattanzi, D., Ciuffoli, S., Burattini, S., Grineland, R.E., Edgerton, V.R., Roy, R.R., Tidball, J.G., Falcieri, E. Growth hormone plus resistance exercise attenuate structural changes in rat myotendinous junctions resulting from chronic unloading. Eur. J. Histochem. v. 57 (4), 2013. PMC3896039
57. Angeli, C., Edgerton V.R., Gerasimenko Y., Harkema S. Altering spinal cord excitability enables voluntary movements after chronic complete paralysis in humans. Brain. 2014 137(Pt 5):1394-409.
58. Ohira, T., Ohira, T., Kawano, F., Shibaguchi, T., Okabe, H., Goto, K., Ogita, F., Sudoh, M., Roy, R.R., Edgerton, V.R., Cancedda, R., and Ohira, Y. Effects of gravitational loading levels on protein expression related to metabolic and/or morphologic properties of mouse neck muscles. Rep. 2014 2:e00183.
59. Nielson JL, Guandique CF, Liu AW, Burke DA, Lash AT, Moseanko R, Hawbecker S, Strand SC, Zdunowski S, Irvine K-A., Brock JH, Rosenzweig ES, Nout YS, Gensel JC, Anderson KD, Segal MR, Magnuson DSK, Whittemore SR, McTigue DM, Popovich PG, Rabchevsky AG, Scheff SW, Steward O, Courtine G, Edgerton VR, Tuszynski MH, Beattie MS, Bresnahan JC, Ferguson AR. Development of a Database for Translational Spinal Cord Injury Research. J Neurotrauma. 31(21):1789-99 2014.
60. Tillakaratne, N.J.K., Duru, P., Fujino, H., Zhong, H., Xiao, M.S., Edgerton, V.R., and Roy, R.R. Identification of Interneurons activated at different inclines during treadmill locomotion in adult rats. Neurosci. Res. 92(12):1714-22. 2014
61. Gad, P.N., Roy, R.R., Zhong, H., Lu, D.L., Gerasimenko, Y.P., and Edgerton, V.R. Initiation of Bladder Voiding with Epidural Stimulation in Paralyzed, Step Trained Rats. PLOS ONE 9(9): e108184. doi:10.1371/journal.pone.0108184. 2014
62. Gerasimenko YP, Gorodnichev R, Puhov A, Moshonkina T, Savochin A, Selionov VA, Roy RR, Lu DC,Edgerton VR. Initiation and modulation of locomotor circuitry output with multi-site transcutaneous electrical stimulation of the spinal cord in non-injured humans.  J Neurophysiol. 2014 113(3):834-42,
63. García-Alías G, Truong K, Shah PK, Roy RR,Edgerton VR. Plasticity of subcortical pathways promote recovery of skilled hand function in rats after corticospinal and rubrospinal tract injuries. Exp Neurol. 2015 (in-press)
64. Duru P., Tillakaratne N.J.K,  Kim J.A, Zhong H., Stauber S., Pham T., Xiao M.S., Edgerton V.R., Roy R.R. Spinal neuronal activation during locomotor-like activity enabled by epidural stimulation and 5-HT agonists in spinal rats. J Neurosci Res, 2015 (in- press).
65. Gad P., Roy R.R., Choe J., Creagmile J., Zhong H., Gerasimenko Y., and Edgerton V.R. Electrophysiological biomarkers of neuromodulatory strategies to recover motor function after spinal cord injury. Neurophysiol. 2015 (accepted).
66. Lavrov I., Musienko P.E., Selionov V.A., Zdunowski S., Roy R.R., Edgerton V.R., and Gerasimenko Y. Activation of spinal locomotor circuits in the decerebrated cat by spinal epidural and/or intraspinal electrical stimulation. Brain Research 1600:84-92. 2015

 

Invited Book Chapters and Reviews (past 10 years)

1. Edgerton, V.R., Tillakaratne, N.J.K., Bigbee, A.J., de Leon, R.D., and Roy, R.R. Locomotor recovery potential after spinal cord injury. IN: Neuro-Behavioral Determinants of Interlimb Coordination. Chapter 3.  P. Swinnen and J. Duysens (eds.), Kluwer Academic Publishers, Dordrecht, Netherlands, pp. 53-91, 2004.
2. Edgerton, V.R., Tillakaratne, N.J.K., Bigbee, A.J., de Leon, R.D., and Roy, R.R. Plasticity of the spinal circuitry after injury. In: Rev. Neurosci. Volume 27, 2004, pp. 145-167
3. Edgerton, V.R. and Roy, R.R. The Nervous System and Movement. ACSM’s Advanced Exercise Physiology. C. Tipton (ed.), Lippincott Williams and Wilkins, Philadelphia, pp. 41-94, 2006.
4. Ichiyama, R.M., Roy, R.R., and Edgerton, V.R. Assessment of sensorimotor function after spinal cord repair. IN: Textbook of Neural Repair and Rehabilitation: Neural Repair and Plasticity. Volume 1, Chapter 30, M.E. Selzer, S. Clarke, L.G. Cohen, P.W. Duncan and F.H. Gage (eds), Cambridge University Press, New York, pp. 548-562, 2006.
5. Edgerton, V.R. and Roy, R.R. Sensorimotor plasticity and control of movement following spinal cord injury. IN: Encyclopedia of Neuroscience. Volume 8, L.R. Squire (ed.), Academic Press, Oxford, pp. 629-635, 2009.
6. Roy, R.R., and Edgerton, V.R. Skeletal muscle architecture. IN: Encyclopedia of Neuroscience.  D. Binder, N. Hirokawa, and U. Windhorst (eds).  Springer-Verlag, Berlin Heidelberg, pp. 3702-3707, 2009.
7. Fong, A.J., Roy, R.R., Ichiyama, R.M., Lavrov, , Courtine, G., Gerasimenko, Y., Tai, Y.C., Burdick, J., and Edgerton, V.R. Recovery of control of posture and locomotion after a spinal cord injury: Solutions staring us in the face.  IN: Neurotherapy: Progress in Restorative Neuroscience and Neurology: Prog. Brain Res. Volume 175, Chapter 30. J. Verhaagen, E.M. Hol, I. Huitenga, J. Winjnholds, A.B. Bergen, G.J. Boer, and D.F. Swaab (eds.), Elsevier Science B.V., Netherlands, pp. 393-418, 2009 PMC2904312
8. Edgerton, V.R., Harkema, S.J., and Roy, R.R. Retraining the human spinal cord: Exercise interventions to enhance recovery after a spinal cord injury. In: Spinal Cord Medicine Principles and Practice, Second edition, Chapter 72. W. Lin (ed), Demos Medical Publishing, LLC, New York, 2010, pp. 939-949.
9. Edgerton, V.R. and Roy, R.R. The nervous system and movement. IN: ACSM’s Advanced Exercise Physiology, Second edition, Chapter 2. P.A. Farrell, M.J. Joyner, V.J. Caiozzo (eds), Lippincott Williams and Wilkins, Philadelphia, 2011, pp. 37-96.
10. Courtine, G., van den Brand, R., Roy, R.R., Edgerton, V.R. Multisystem Neruorehabilitation in Rodents with Spinal Cord Injury. IN: Neurorehabilittion Technology, Part 1. V. Eietz, T. Nef, W.Z. Rymer (eds), Springer Ltd, London, 2012, pp. 3-22.
11. Kim, J.A., Roy, R.R., and Edgerton, V.R. Neuromechanical Interactions that Control Muscle Function and Adaptation. Muscle: Fundamental Biology and Mechanisms of Disease. Elsevier, New York, 2012, pp. 789-800.

 

Books Published

1. Edington,D.W and V. R. Edgerton. Biology of Exercise, Houghton Mifflin, 1976
2. Edington,D.W and V. R. Edgerton. Biology of Exercise, Houghton Mifflin, 1976; (translated in Japanese by Yoshi Ohira, 1991)
3. Stevens, S.L., Haines, D.E., Meyer, D.M. and Edgerton, V.R. An Atlas and Source Book of the Lesser Bushbaby, Galago senegalensi  CRC Press, Boca Raton, Florida, 1981.
4. Cole, Ted and Edgerton, V.R. Medical Rehabilitation Research:  A Report of the Panel on Physical Medicine and Rehabilitation Research.  Co-Chairs to the Advisory Committee to the Director, National Institute of Health, Bethesda, Maryland, 1989.
5. Shimamura, S. Grillner and V.R. Edgerton. Neurobiological Basis of Human Locomotion.  Japan Scientific Societies Press, Tokyo, 1991.

 

 

Dr. rer. nat. Karim Fouad (Dipl. Biol.), Professor University of Alberta, Faculty of Rehabilitation Medicine Department of Physical Therapy, and Centre for Neuroscience, Edmonton, AB.

Scientific career:

2009-present: Professor, Department of Physical Therapy in the Faculty of Rehabilitation Medicine and Centre for Neuroscience

2009-2015: Professor, Faculty of Rehabilitation Medicine

2007-2014: Senior Scholar, Alberta Heritage Foundation for Medical Research

2005-2009: Associate Professor, Faculty of Rehabilitation Medicine

2002-2007: Scholar, Alberta Heritage Foundation for Medical

2001-2005: Assistant Professor, Faculty of Rehabilitation Medicine University of Alberta, Edmonton, Canada,

1997-2001: Post-Doctoral Fellow/Research Associate, Brain Research Institute and Swiss Paraplegic Centre Balgrist, University and ETH Zürich, Switzerland,

1995-1997: Post-Doctoral Researcher, University of Alberta, Edmonton, Canada

1991-1995: Graduate studies, University of Konstanz, Germany

1986-1991: Diploma (Biology), University of Konstanz, Germany

 

Funding history: (Principal Investigator unless otherwise noted)

2014: Equipment grant form the Alberta Paraplegic Foundation

2013-2018: Co-PI onGrant from the Canadian Institute for Health Research: Patterned electrical stimulation of the arms and legs to improve walking after spinal cord injury

2012-2015: Grant from the International Spinal Research Trust, UK: Activating neuron-intrinsic programs in sensory and cortico spinal neurons for axonal regeneration

2012-2017: Grant from the Canadian Institute for Health Research: Roles of cAMP and training in the recovery of reaching after spinal cord injury

2012-2017: Grant from the Canadian Institute for Health Research: Recovery of locomotion mediated by interneuron regeneration following complete spinal cord injury

2009-2011: Grant from Wings for Life, Austria: Mutli-component treatment to promote axonal regeneration: rat studies to parallel primate experiments

2008-2011: Grant from the International Spinal Research Trust, UK: Rewiring the central nervous system following spinal cord injury using neurotrophins and rehabilitative training

2007-2008: Research Agreement with Wyeth Pharmaceuticals, USA: Testing TrkB agonist

2007-2014: Alberta Heritage Foundation for Medical Research – Salary Award: Combining axonal growth promoting treatments with rehabilitative training

2006: Major Equipment Grant from AHFMR

2006-2008: Grant from the Christopher and Dana Reeve Foundation, USA: Cyclic AMP and training to promote regeneration and functional recovery after spinal cord injury

2005-2007: Co-investigator on a grant from the Christopher and Dana Reeve Foundation: Retraining of walking skills after spinal cord injury

2005-2010: Grant from the Canadian Institute for Health Research: Combining axonal growth promoting treatments with rehabilitative training

2005-2010: Grant from the Natural Science and Engineering Council of Canada: Integrating neural stem cells into injured neuronal networks

2005: Grant from the Canadian Institute for Health Research: Combining axonal growth promoting treatments with rehabilitative training

2004: Small Faculty Research ProgramGrant, University of Alberta

2003-2006: Grant from the International Spinal Research Trust, UK: Enhancing the role of propriospinal interneurons in the recovery of motor function after spinal cord injury

2003: New Opportunities Award from the Canadian Foundation for Innovation: Combining axonal growth promoting treatments with rehabilitative training

2002-2004: AHFMR: Combining axonal growth promoting treatments with training

1995-1997: Postdoctoral Fellowship from the German Research Council: Plasticity in afferent pathways controlling locomotion (salary award)

 

Publications: (last 5 years only, students underlined)

Peer reviewed articles:

FenrichKK, May Z, Hurd C, Bennett DJ, Boychuk C, Whishaw IQ and Fouad K (2014) Improved single pellet grasping using automated ad libitum full-time training robot. Behav Brain Res 16, 281:137-148

Helmbrecht MS, Soellner H, Truckenbrodt AM, Sundermeier J, Cohrs C, Hans W, de Angelis MH, Feuchtinger A, Aichler M, Fouad K, Huber AB (2014) Loss of Npn1 from motor neurons causes postnatal deficits independent from Sema3A signaling. DevBiol S0012-1606(14)00612-5

Fouad K and Hurd C (2014) Repairing the injured spinal cord: sprouting versus regeneration. Is this a realistic match?Neural Regen Res 9, 462

Weishaupt N, Mason AL, Hurd C, May Z, Zmyslowski DC, Galleguillos D, Sipione S, Fouad  (2014) Vector-induced NT- 3 expression in rats promotes collateral growth of injured cortico spinal tract axons far rostral to a spinal cord injury. Neuroscience 272: 65-75

Fouad K, Hurd C and Magnuson DS (2013) Functional testing in animal models of spinal cord injury: not as straight forward as one would think. Front IntegNeurosci. 7, 85.

Sist B, Fouad K, and Winship IR (2013) Plasticity beyond peri-infarct cortex: Spinal up regulation of structural plasticity, neurotrophins, and inflammatory cytokines during recovery from cortical stroke. ExpNeurol252, 47-56

Fouad K, Bennett DJ, Vavrek R and Blesch A (2013) Long-Term Viral Brain-Derived Neurotrophic Factor Delivery Promotes Spasticity in Rats with a Cervical Spinal Cord Hemisection. Front Neurol, 19;4:187.

Hurd C, Weishaupt N and Fouad K (2013) Anatomical correlates of recovery in single pellet

reaching in spinal cord injured rats. ExpNeurol247:605-14

Li Y, Li L, Stephens MJ, Zenner D, Murray KC, Winship I, Vavrek R, Baker GB, Fouad K and Bennett DJ (2013) Synthesis, transport and metabolism of serotonin formed from exogenously applied 5-HTP after spinal cord injury in rats. J Neurophysiol 111, 145-63

Weishaupt N, Krajacic A and Fouad K (2013) Lipopolysaccharide can induce errors in anatomical measures of neuronal plasticity by increasing tracing efficacy.NeurosciLett556, 181-5.

Weishaupt N, Hurd C, Wei DZ and Fouad K(2013) Reticulospinal plasticity after cervical spinal cord injury in the rat involves withdrawal of projections below the injury. ExpNeurol247:241-9

Weishaupt N,Vavrek R and Fouad K (2013) Training following unilateral cervical spinal cord injury in rats affects the contralesional forelimb. NeurosciLett, 28;539:77-81.

Weishaupt N, Li S, Di Pardo A, Sipione S and Fouad K (2013) Synergistic effects of BDNF and rehabilitative training on recovery after cervical spinal cord injury. Behav Brain Res 15; 239:31-42.

Lu P, Blesch A, Graham L, Wang Y, Samara R, Banos K, Haringer V, Havton L, Weishaupt N, Bennett D, Fouad K and Tuszynski MH (2012) Motor axonal regeneration after partial and complete spinal cord transection. J Neurosci, 13, 8208-18.

Sławińska U, Rossignol S, Bennett DJ, Schmidt BJ, Frigon A, Fouad K and Jordan LM (2012) Comment on «Restoring voluntary control of locomotion after paralyzing spinal cord injury». Science 19; 338 (6105):32

Di Pardo A, Maglione V, Alpaugh M, Horkey M, Atwal RS, Sassone J, CiammolaA, Steffan JS, Fouad K, Truant R and Sipione S (2012) Ganglioside GM1 induces phosphorylation of mutant Huntington and restores normal motor behavior in Huntington’s disease mice. PNAS, 109: 3528-33

Henderson AK, Galic MA, Fouad K, Dyck RH, Pittman QJand Teskey GC (2011) Larger cortical motor maps after seizures. Eur J Neurosci 34, 615-21.

Fouad K, Rank MM,Vavrek R, Murray KC, Sanelli L and Bennett DJ (2010) Locomotion after spinal cord injury depends on constitutive activity in serotonin receptors. J Neurophysiol 104: 2975-84.

Krajacic A, Weishaupt N, Girgis J and Fouad K (2010) Training-induced plasticity in rats with cervical spinal cord injury: Effects and side effects. Behav Brain Res, 214, 323-33.

Fouad K, Vavrek R and Cho S. (2010) A TrkB antibody agonist promotes plasticity following cervical spinal cord injury in adult rats.J Neurotrauma, Jul 2, Epub ahead of print.

Weishaupt N, Silasi G, Colbourne F and Fouad K (2010) Secondary damage in the spinal cord following motor cortex injury in rats.J Neurotrauma, 27, 1387-97.

Murray KC, Nakae A, Stephens MJ, Rank M, D’Amico J, Harvey PJ, Li X, Harris RL, Ballou EW, Anelli R, Heckman CJ, Mashimo T, Vavrek R, Sanelli L, Gorassini MA, Bennett DJ, and Fouad K (2010) Recovery of motoneuron and locomotor function after spinal cord injury depends on constitutive activity in 5-HT(2C) receptors. Nature Med, Jun; 16(6), 694-700.

Fouad K, GhoshM, VavrekR, Tse AD and Pearse DD (2009) Dose and chemical modification considerations for continuous Cyclic AMP analog delivery to the injured CNS. J Neurotrauma, 26, 733-740.

Fouad K, Pearse DD, Tetzlaff W and Vavrek R (2009) Combined cell implantation and chondroitinase delivery prevents deterioration of bladder function in rats with complete spinal cord injury. Spinal Cord, 47, 727-732.

Mussleman KE, Fouad K, Misiaszek JE and Yang JF (2009) Training of walking skills overground and on the treadmill: case series on individuals with incomplete SCI. PhysTher89, 601-11.

Krajacic A, GhoshM, PuentesR, PearseDD and Fouad K (2009) Advantages of delaying the onset of rehabilitative reaching training in rats with incomplete spinal cord injury. Eur J Neurosci, 29, 641-651.

 

Book chapters and reviews:

Fouad K, Forero, J and Hurd C (2015) A simple analogy for nervous system plasticity after injury.Exerc Sport Sci Rev, Epub ahead of print

Zheng B, and Fouad K (2013) Myelin associated growth inhibitors. In: Selzer M, Clarke S, Cohen L, Duncan P and Gage F, eds, Textbook of Neural Repair & Rehabilitation, 2^nd edition; Cambridge University Press, in press.

Dietz V, and Fouad K (2013) Restoration of sensorimotor functions after spinal cord injury. Brain. 37, 654-67

Weishaupt N,Blesch A, Fouad K (2012) BDNF: The career of a multifaceted neurotrophin in spinal cord injury. ExpNeurol 238, 254-64.

Fouad K, Bennett, Fischer H and A Bueschges (2012) Comparative Psychology of Motor Systems. In: Nelson RJ, Gallagher M and Weiner IB, eds, Handbook of Psychology, Volume 4: Biological Psycology, Wiley, in press.

Fouad K and Tetzlaff W (2011) Rehabilitative training and plasticity following spinal cord injury.ExpNeurol, Epub ahead of print.

Onifer S, Smith G and Fouad K (2011) Plasticity after spinal cord injury: relevance to recovery and approaches to facilitate it.  Neurotherapeutics 34, 283-93.

Kwon BK, Okon EB, Plunet W, Baptiste D, Fouad K, Hillyer J, Weaver LC, Fehlings MG, Tetzlaff W. (2010) A Systematic Review of Directly Applied Biologic Therapies for Acute Spinal Cord Injury. J Neurotrauma. Jun 16. [Epub ahead of print].

Fouad K, Krajacic A, and Tetzlaff W (2010) Spinal cord injury and plasticity: Opportunities and challenges. Brain Res Bull. 84. 337-342].

Tetzlaff W, Fouad K and Kwon B (2009) Be careful what you train for. Nature Neuroscience, 12, 1077-9.

M.D, Ph.D, F.A.C.S., F.R.C.S.(C) Clinical Professor, Department of Neurological Surgery. Miami Project, USA.

 

J Guest MD, PhD. FACS is a board certified neurosurgeon who received his scientific, PhD, training under the mentorship of Richard and Mary Bunge from 1993-1996. Dr. Guest has been active in translational research of cell therapy and neuroprotection. He helped lead the Miami Project group in acquiring an IND through the US FDA to conduct trials of autologous Schwann cell transplantation in subjects with subacute SCI, and subsequently into those with chronic SCI. Dr. Guest serves as an advisor or reviewer for several entities including the FDA and the California Institute of Regenerative Medicine. He is site PI for the North American Clinical Trials Network. His research focus has been on the translational testing of cell transplantation in large animal models. Key recent publications include:

1.  Soderblom, C., D. H. Lee, A. Dawood, M. Carballosa, A. Jimena Santamaria, F. D. Benavides, S. Jergova, R. M. Grumbles, C. K. Thomas, K.  K. Park, J. D. Guest, V. P. Lemmon, J. K. Lee and P. Tsoulfas (2015). «3D Imaging of Axons in Transparent Spinal Cords from Rodents and  Nonhuman Primates.» eNeuro 2(2).
2. Guest, J., A. J. Santamaria and F. D. Benavides (2013). «Clinical translation of autologous Schwann cell transplantation for the treatment of spinal cord injury.» Curr Opin Organ Transplant 18(6): 682-689.
3. Grossman, R. G., M. G. Fehlings, R. F. Frankowski, K. D. Burau, D. S. Chow, C. Tator, A. Teng, E. G. Toups, J. S. Harrop, B. Aarabi, C. I. Shaffrey, M. M. Johnson, S. J. Harkema, M. Boakye, J. D. Guest and J. R. Wilson (2014). «A prospective, multicenter, phase I matched-comparison group trial of safety, pharmacokinetics, and preliminary efficacy of riluzole in patients with traumatic spinal cord injury.» J Neurotrauma 31(3): 239-255.
4. Grossman, R. G., R. F. Frankowski, K. D. Burau, E. G. Toups, J. W. Crommett, M. M. Johnson, M. G. Fehlings, C. H. Tator, C. I. Shaffrey, S. J. Harkema, J. E. Hodes, B. Aarabi, M. K. Rosner, J. D. Guest and J. S. Harrop (2012). «Incidence and severity of acute complications after spinal cord injury.» J Neurosurg Spine 17(1 Suppl): 119-128.

 

Dr. Jerry Silver. Professor Department of Neurosciences Case Western Reserve University, USA.

Dr. Silver received his Ph.D. from Case Western Reserve in 1974 and was the recipient of the Herbert S. Steuer Memorial Award for Meritorious Original Research in Anatomy. He did post-doctoral work at Harvard University in the Department of Neurosciences at The Children’s Hospital and in the Neuropathology Department at Harvard Medical School.  Dr. Silver is currently Professor in the Department of Neurosciences at the Case Western Reserve University School of Medicine and adjunct Professor in the Department of Neurosurgery at the Cleveland Clinic Foundation. Dr. Silver is a recipient of several prestigious awards. In 2003 he was awarded the Ameritec Prize for significant accomplishments toward a cure for paralysis. This prize was established in 1987 specifically to recognize scientists whose research advances the search towards a cure for paralysis.  In 2003 he was also honored with the Christopher Reeve-Joan Irvine Research Medal  (The Reeve-Irvine Medal) for critical contributions that may lead to the promotion of repair of the damaged spinal cord.  The prize acknowledges the most meritorious science, a proven body of work that has withstood the test of time and scrutiny, as well as other enriching contributions to the field.  In 2004 Dr. Silver received a Jacob Javits Neuroscience Investigator Award for his long-standing grant entitled “Factors affecting regeneration through the glial scar.” This is a highly prestigious award that recognizes a select group of NIH grantees who have made seminal contributions to their field of neuroscience, have contributed exemplary service to the NIH, and who show great promise for continuing their cutting edge research well into the future. Dr. Silver was named the recipient of the 2008 Erica Nader Award, which is given through the American Spinal Injury Association (ASIA).  The award honors “breakthrough research in the field of spinal cord injury”.  In 2011 he was honored to become a fellow of the American Association for the Advancement of Science (AAAS). Dr. Silver has served on a number of editorial boards including the journals Glia, The Journal of Neurocytology, Developmental Neurobiology, The Journal of Neuroscience and Experimental Neurology (where he is a Section Editor). He regularly reviews articles for over 35 high impact journals and he reviews grants for 18 national and international organizations.  He has served on a variety of NIH study sections since 1982 including the Neurobiology Review Group, Neurology B2, The Visual Sciences C Study Section, and the Clinical Neurology, Neurotransmitters and Transplantation Study Section.   He has been appointed as a regular member of the Scientific Advisory Council of the Christopher Reeve Foundation and of the Scientific Board of the International Spinal Research Trust (England).  He has served as lead or senior author on more than 160 publications.

Dr. Marina Mata, Professor of Neurology, University of Michigan School of Medicine, Physician at the affiliated VA Ann Arbor Healthcare System, USA.

Dr. Marina Mata is Professor of Neurology at the University of Michigan Medical School in Ann Arbor MI. She graduated from the University of Barcelona Medical School, trained in Medicine at Valle d’Hebron Hospital in Barcelona and in Neurology at the University of Michigan. Dr. Mata completed a research fellowship at the US National Institutes of Health as a Fogarty Fellow, and a second post-doc at the University of California in San Francisco.

Dr. Mata’s research has been focused on the neurobiology of axons, their response to injury and strategies for neural repair. She has been a pioneer in the use of herpes simplex virus-based vectors for gene delivery in models of spinal cord injury, peripheral neuropathy and pain. She participated in the first human clinical trials using HSV-based vectors for the treatment of intractable pain, and will discuss preclinical data towards development of treatment for SCI using the HSV vector platform.

Dr. Phillip Popovich, PhD Professor, Director Department of Neuroscience , Center for Brain and Spinal Cord Repair Ray W. Poppleton Designated Research Chair Wexner Medical Center at The Ohio State University (USA)

BIOGRAPHICAL SKETCH

Provide the following information for the Senior/key personnel and other significant contributors.
Follow this format for each person.  DO NOT EXCEED FIVE PAGES.

NAME: Phillip G. Popovich

eRA COMMONS USER NAME (credential, e.g., agency login): POPOVICH02

POSITION TITLE: Professor

EDUCATION/TRAINING (Begin with baccalaureate or other initial professional education, such as nursing, include postdoctoral training and residency training if applicable. Add/delete rows as necessary.)

INSTITUTION AND LOCATION	DEGREE (if applicable)	Completion Date MM/YYYY	FIELD OF STUDY
The Pennsylvania State University	B.S.	1990	Biology/Physiology
The Ohio State University	PhD	1995	Physiology (Spinal Cord Injury/SCI)
The Ohio State University	Postdoctoral Fellowship	1997	Immunology
The Ohio State University	Research Scientist	1999	Neuroimmunology and SCI

A. Personal Statement

I received my PhD in Physiology with an emphasis on understanding the neuro-immune consequences of traumatic spinal cord injury (SCI). My post-doc training emphasized didactic and experimental training in Immunology. As such, my research training is interdisciplinary and all research programs in my laboratory approach the problem of SCI from a “systems” or whole-body perspective. My entire career has been focused on the problem of SCI and over the years, I have established collaborations throughout the world with colleagues that have sought my neuroimmunology expertise in their research programs. At Ohio State, I serve as Director for the Center for Brain and Spinal Cord Repair (CBSCR). The CBSCR is a group of scientists with research and clinical expertise focused primarily in SCI; however, a growing nucleus of researcher also have started working on models and problems related to traumatic brain injury (TBI). At OSU, we have a strong and diverse technical infrastructure for both SCI and TBI research and an extensive surgical, animal care and behavioral core facility that serves this research group. I have been continuously funded by the NIH since the inception of my lab and currently serve as PI or co-Investigator on multiple NIH- and DoD-funded grants focused on areas related to neuroimmunology and SCI. Below, are four citations from my lab that illustrate my lab’s expertise in modeling SCI, manipulation of innate and adaptive immunity and systems-level biology with translational applicability to the problem of SCI.

 

1. POPOVICH, P.G., Guan, Z., Wei, P., Yu, J.Y., Huitinga, I., van Rooijen, N., Stokes, B.T. Depletion of hematogenous macrophages promotes partial hindlimb recovery and neuroanatomical repair after experimental spinal cord injury. Neurol., 158(2):351-365, 1999. PMID:10415142
2. Jones, T.B., Basso, D.M., Sodhi, A., Pan, J.Z., Hart, Hart, R.P., MacCallum, R.C., Lee, S., Whitacre, C.C., POPOVICH, P.G. Pathological central nervous system autoimmune disease is triggered by traumatic spinal cord injury: implications for autoimmune vaccine therapy, Neuroscience, 22: 2690-2700, 2002. PMID:11923434
3. Kigerl, K.A., Gensel, J.C., Ankeny, D.P., Alexander, J.A. Donnelly, D.J. and POPOVICH, P.G. Identification of two distinct macrophage subsets with divergent effects causing either neurotoxicity or regeneration in the injured mouse spinal cord, Neurosci., 29(43):13435-44, 2009. PMID:19864556 PMC:2788152
4. Zhang, Y., Guan, Z, Reader, B, Shawler, T., Mandrekar-Colucci, S., Huang, K., Weil, Z., Bratasz, A., Wells, J., Powell, N.D., Sheridan, J.F., Whitacre, C.C., Rabchevsky, A.G., Nash, M.S. and POPOVICH, P.G. Autonomic dysreflexia suppresses immune function after spinal cord injury. Neurosci., 33 12970-12981, 2013.

B.Positions and Honors

Positions and Employment

1995-1997 – Sandoz Research Scholar, The Sandoz Corporation and The Ohio State University (OSU)

1997-1999 – Adjunct Assistant Professor, Dept. Medical Microbiology & Immunology, OSU

1999-2004 – Assistant Professor (Tenure Track), Dept of Molecular Virology, Immunology & Medical Genetics (MVIMG), OSU

2003-4   Assistant Professor (Joint Appointment), Department of Neuroscience, OSU

2004-8   Associate Professor (with Tenure), Depts. MVIMG and Neuroscience, OSU

2006-     Ray W. Poppleton Research Designated Chair

2006-     Director, OSU Center for Brain and Spinal Cord Repair (CBSCR)

2008-     Professor, Neuroscience and Neurosurgery, The Ohio State University

2013:      Visiting Professor, Deutsches Zentrum fur Neurodegenerative Erkrankungen (DZNE)/German Center for Neurodegenerative Diseases, Bonn, Germany

Other Experience and Professional Memberships

1998-2000 – Reviewer, Paralyzed Veterans of America – Spinal Cord Research Foundation Research Grants

2001-2008 – Reviewer, California Roman Reed Initiative to fund SCI Research

1999, 2002-4 – Ad-Hoc Review, NIH Brain Disorders & Clinical Neuroscience-2 (BDCN-2) Study Section

2004-2008 – Member, NIH Clinical Neuroplasticity and Neurotransmitters Study Section (CNNT)

2001 – Reviewer, Canadian Institutes of Health Research

2002, 2003 – Reviewer, Christopher Reeve Paralysis Foundation

2004 – Reviewer, International Spinal Research Trust (Spinal Cord Foundation, UK) (2004-)

2007-12 – Ad-hoc Reviewer, Craig H. Neilsen Foundation

2007-13 – Reviewer, Wings for Life Foundation

2004-2008; 2013-present – Councilor, National Neurotrauma Society

2007 – Vice President, National Neurotrauma Society

Editorial Board: Experimental Neurology (2009), Journal of Neurodegeneration and Regeneration (2008); Associate Editor, BMC Neurology (2009-)

2007- Reviewer, Department of Defense Post-Traumatic Stress Disorder and Traumatic Brain Injury

2009-present: Member, Advisory Board, VA SCI Translational Collaborative Centers

2011-12                Strategic Planning Committee, National Neurotrauma Society

2010-present: Member, Scientific Advisory Board: Mission Connect

2012-present: Member, Scientific Review Board (standing member): Craig H. Neilsen Foundation

2012-15:               Member, Scientific Advisory Board: Unite 2 Fight Paralysis

2015-present: Chair, Scientific Advisory Board: Unite 2 Fight Paralysis

 

Honors

1993-95: NINDS Neural Development, Plasticity, and Regeneration Training Grant Award

1995-97: Special Medical Research Fellowship, The Sandoz Corporation and The Ohio State University

1997:     Michael E. Goldberger Award for Research in Neural Regeneration

1999:     US Patent: (#5,932,563) – Methods for Treating Spinal Cord Injury

2003:     Excellence in Teaching Award, OSU College of Medicine and Dept. MVIMG

2006:     Ray W. Poppleton Research Designated Chair

2013:     Fellow, American Association for the Advancement of Science (AAAS)

C.Contribution to Science

Microglia, Macrophages and Spinal Cord Injury (Innate Immunity)

My lab published the first papers documenting the time course, composition, distribution and functional implications of infiltrating leukocytes in spinal cord contusion models of SCI using various rat and mouse strains. Using both rat and mouse models of SCI, we discovered that resident CNS macrophages (microglia) dominate the lesion and surrounding spinal tissue for up to 3 days prior to the onset of monocyte infiltration into the injured spinal cord. Also, as monocytes differentiate into macrophages, they become phenotypically and functionally distinct  cells that persist indefinitely at the site of trauma.  Depletion of circulating monocytes, beginning at one day post-injury and continuing through the first week post-injury, confers significant neuroprotection and improves functional recovery. Importantly, those pre-clinical data have been independently replicated in many laboratories using various species and SCI models and different mechanisms of macrophage depletion. These collective data also have served as benchmarks or guidelines for other laboratories that subsequent described neuroinflammatory changes in injured human spinal cord specimens.

1. POPOVICH, P.G., Wei, P., Stokes, B.T. The cellular inflammatory response after spinal cord injury in Sprague-Dawley and Lewis rats. Comp. Neurol., 377(3), 443-464, 1997. PMID:8989657
2. POPOVICH, P.G., Guan, Z., Wei, P., Yu, J.Y., Huitinga, I., van Rooijen, N., Stokes, B.T. Depletion of hematogenous macrophages promotes partial hindlimb recovery and neuroanatomical repair after experimental spinal cord injury. Neurol., 158(2):351-365, 1999.
3. POPOVICH, P.G. and Hickey, W.F. Bone-marrow chimeric rats reveal the unique distribution of resident and recruited macrophages in the contused rat spinal cord, Neuropathol. Exp. Neurol., 60(7) 676-685, 2001. PMID:11444796
4. Kigerl, K.A., Gensel, J.C., Ankeny, D.P., Alexander, J.A. Donnelly, D.J. and POPOVICH, P.G. Identification of two distinct macrophage subsets with divergent effects causing either neurotoxicity or regeneration in the injured mouse spinal cord, Neurosci., 29(43):13435-44, 2009. PMID:19864556 PMC:2788152

 

Lymphocytes, Autoantibodies and Spinal Cord Injury (adaptive immunity)

During my PhD dissertation research, I developed the hypothesis that SCI enhances bidirectional communication between the CNS and lymphocytes in peripheral lymphoid tissues. Applying concepts and laboratory techniques used in the animal model for multiple sclerosis, I found that SCI activates T lymphocytes that recognize myelin-basic protein (MBP) and that these T cells, once activated, migrate into the intact CNS where they cause pathology and neurological impairment. From those studies, I concluded that sterile CNS trauma triggers an autoimmune process, a response that I designated “trauma-induced autoimmunity”. That observation served as the basis for independent follow-up studies in human SCI (Kil et al., 1999). T cells release factors that directly influence neuron survival and function; however, indirect effects also are mediated via activation of other leukocytes including B lymphocytes and macrophages. Novel data from my lab showed that a mid-thoracic SCI activates B lymphocytes leading to an increase in circulating autoantibodies with pathogenic potential. In collaboration with others, we confirmed that similar autoantibody responses occur in SCI humans.

1. POPOVICH, P.G., Stokes, B.T., Whitacre, C.C. The concept of autoimmunity following spinal cord injury: possible roles for T-Lymphocytes in the traumatized CNS. J. Neurosci. Res., 45, 349-363, 1996. PMID:8872895
2. Jones, T.B., Basso, D.M., Sodhi, A., Pan, J.Z., Hart, Hart, R.P., MacCallum, R.C., Lee, S., Whitacre, C.C., POPOVICH, P.G. Pathological central nervous system autoimmune disease is triggered by traumatic spinal cord injury: implications for autoimmune vaccine therapy, J. Neuroscience, 22: 2690-2700, 2002. PMID:11923434
3. Hayes, K.C., Hull, T.C.L., Delaney, G.A., Potter, P.J., Sequeira, K.A.J., Campbell, K., POPOVICH, P.G. Elevated serum titers of proinflammatory cytokines and CNS autoantibodies in patients with chronic spinal cord injury, J. Neurotrauma, 19(6): 753-761, 2002. PMID:12165135
4. Ankeny, D.P., Guan, Z. and POPOVICH, P.G. B cells produce pathogenic antibodies and impair recovery after spinal cord injury in mice, J. Clin. Invest., 119(10):2909-9, 2009. PMID:19770513 PMC:2752085

 

Autonomic Control of Immune Function after SCI

In contrast to mid-thoracic SCI, which potentiates autoimmunity (see above), injury to the upper thoracic or cervical spinal cord impairs immune function, potentially explaining why the incidence of infectious morbidity and mortality is high in this SCI population. My lab showed that SCI at T3 spinal level (but not T9) increases circulating levels of glucocorticoids (GCs) and causes profound dysregulation of the sympathetic nervous system (SNS) resulting in enhanced leukocyte apoptosis and subsequent immune suppression. Synergistic activation of leukocyte glucocorticoid receptors (GRs) and beta-2 adrenergic receptors (β2ARs) were identified as mechanisms underlying SCI-induced apoptosis and immune suppression; systemic injections of selective GR and β2AR antagonists block acute SCI-induced immune suppression. This is clinically important since immune suppression is a chronic problem in both animals and people with SCI and the mechanisms underlying this pathology are unknown. My lab also found that autonomic dysreflexia, a life-threatening complication that is unique to high-level SCI, may be a mechanism that explains chronic SCI-induced immune depression.

1. Lucin, K.M., Sanders, V.M., Jones, T.B., Malarkey, W.B., POPOVICH, P.G. Impaired antibody synthesis after spinal cord injury is level-dependent and is due to sympathetic nervous system dysregulation, Experimental Neurology, 207(1):74-84, 2007. PMID:17597612 PMC:2023967
2. Zhang, Y., Guan, Z, Reader, B, Shawler, T., Mandrekar-Colucci, S., Huang, K., Weil, Z., Bratasz, A., Wells, J., Powell, N.D., Sheridan, J.F., Whitacre, C.C., Rabchevsky, A.G., Nash, M.S. and POPOVICH, P.G. Autonomic dysreflexia suppresses immune function after spinal cord injury. J. Neurosci., 33 12970-12981, 2013.
3. Rabchevsky, AG, Patel, SP, Lyttle, TS, Eldahan, KC, O’Dell, CR, Zhang, Y, POPOVICH, PG, Kitzman, PH and Donohue, KD. Gabapentin alleviates muscle spasticity and both induced as well as spontaneous autonomic dysreflexia after complete spinal cord injury. Frontiers in Physiol., 3:1-12, 2012.

 

Replication

More than 10 years ago, the NIH issued a call for “SCI replication” contractors. In 2008, my collaborators and I were awarded one of two NIH contracts designed to replicate promising published data in the field of SCI. Designated as an “NIH Facility of Research Excellence in Spinal Cord Injury – Replication”, our group performed five replication experiments. We successfully replicated one published pre-clinical study and partially replicated two others. As a result of this experience, my colleagues and I have helped to establish new reporting and experimental design criteria that we hope will improve experimental rigor and transparency in data reporting with the goal of improving replication success and clinical translation of experimental findings in the field of SCI research.

4. POPOVICH, P.G., Gensel, J.C. and Tovar, C.A. Independent evaluation of the effects of glibenclamide on reducing progressive hemorrhagic necrosis after cervical spinal cord injury. Exp. Neurol., Ahead of Press, 2010. PMID:21145891
5. Steward, O., POPOVICH, P.G., Dietrich, W.D. and Kleitman, N. Replication and reproducibility in spinal cord injury research, Exp. Neurol., 233(2):597-605, Feb 2012. PMID:22078756
6. Lemmon, VP, Ferguson, AR, POPOVICH, PG, Xu, XM, Snow, DM, Igarashi, M, Beattie, CE, Bixby, JL. Minimum Information About a Spinal Cord Injury Experiment (MIASCI) – a proposed reporting standard for spinal cord injury experiments. J. Neurotrauma., Aug 1;31(15):1354-61. doi: 10.1089/neu.2014.3400. Epub 2014 Jul 11. PMID: 24870067
7. Nielson, J.L., Guandique, C.F., Liu, A.W., Burke, D.A., Lash, A.T., Moseanko, R, Hawbecker, S., Strand, S.C., Zdunowski, S., Irvine, K.-A., Brock, J.H., Nout-Lomas, Y.S., Gensel, J.C., Anderson, K.D., Segal, M.R., Rosenzweig, E.S., Magnuson, D.S.K., Whittemore, S.R., McTigue, D.M., POPOVICH, P.G., Rabchevsky, A.G., Scheff, S.W., Steward, O., Courtine, G., Edgerton, V.R., Tuszynski, M.H., Beattie, M.S., Bresnahan, J.C., Ferguson, A.R. Development of a Database for Translational Spinal Cord Injury Research. J. Neurotrauma 2014 Nov 1;31(21):1789-99. doi: 10.1089/neu.2014.3399. Epub 2014 Jul 31.PMID:25077610

 

Complete List of my published work: http://www.ncbi.nlm.nih.gov/pubmed/?term=Popovich-P

D.Research Support

Ongoing Research Support

 

R01NS083942                    Popovich (PI)                                                                                                     09/30/2014-10/01/2019

Preventing autonomic dysreflexia to promote immune function after spinal cord injury

• This grant provides funding to overcome the immune suppressive effects of high-level SCI in mice by blocking systemic stress pathways or through the use of novel neural repair strategies

 

R01 NS047175                   Popovich (PI)                                                                                                     02/15/09-01/31/14  [no-cost extension through 01/16]

Lymphocyte functions in the injured spinal cord

• This grant provides funding to identify molecular targets of autoantibodies produced after spinal cord injury and block/attenuate B cell activation in SCI animals.

 

R01 AG033028                  Godbout (PI)                                                                                                                      09/31/09-08/31/14 [no-cost extension through 08/15]

Aging, microglia dysregulation and depression

• This 5 year grant provides funding to studying the interrelationship between aging and innate immune system dysregulation.

 

R01 NS072304-01             Popovich (PI)                                                                                                     08/15/11-07/31/14 [no-cost extension through 07/15]

TREM2 regulation of macrophages in spinal cord injury and CNS endogenous repair

• This 3 year grant provides funding to study the role of triggering receptor expressed on myeloid cells (TREM2) in rodent models of SCI.

 

OSU2013 20012207         McTigue (PI)                                                                                                                      01/01/14-12/31/18

Spinal Cord Injury Training Program

• This 5 year grant provides funding to support a 2 week training program for SCI

 

R01 NS082095                   McTigue (PI)                                                                                                                      08/01/13-07/31/18

Restoring iron homeostasis to promote recovery after spinal cord injury

• This 5 year grant provides funding to study the role of

 

W81XWH-13-1-0356        Popovich (PI)                                                                                                     09/30/13-09/29/16

Reversing maladaptive plasticity to cure autonomic dysreflexia after spinal cord injury

• This 3 year grant provides funding to study the role of manipulating molecular plasticity in the injured spinal cord.

 

R01 NS043246                   McTigue (PI)                                                                                                                      07/01/11-06/30/16

Axons and the extracellular matrix in spinal cord injury

• This 5 year grant provides funding to study the role of astrocytes and inflammation in creating a glial scar after SCI.

 

R21 NS081413                   Popovich (PI)                                                                                                     09/01/12-08/31/14 [no-cost extension through 08/15]

miRNA regulation of macrophage after spinal cord injury

• This 2 year grant provides funding to study the role of miRNAs in regulated macrophage phenotype and function in mouse models of traumatic spinal cord injury

 Institute of Infection, Immunity and Inflammation, Sir Graeme Davies Building, University of Glasgow

Prof Barnett read Biochemistry at the University of Sheffield followed by a PhD at the Institute of Cancer Research, University of London. She was a Visiting Fogarty Fellow at the National Cancer Institute, NIH, in Bethesda, Maryland. Her next post doctoral training position was at the Ludwig Institute in London in the laboratory of Prof Mark Noble, an eminent glial biologist who identified the oligodendrocyte progenitor cells in the 1980s. Here Prof Barnett gained her experience in neuroscience and glial cell biology as well as regenerative medicine and cell transplantation as a strategy for CNS repair. She also, identified a method to purify and grow olfactory ensheathing cells in. She was a co-author on one of the first papers to transplant oligodendrocyte progenitor cells into a rat model of CNS injury (Nature 362:453-5).

In 1990 she was awarded her first grants which she took to start her laboratory (Glial Cell Biology Group) at the University of Glasgow.  She was awarded a Wellcome Trust University Award in 1998 which led to tenure, and was a Multiple Sclerosis of Great Britain Senior Research Fellow in 2002. Currently she is professor of Cellular Neuroscience, at the Institute of Infection, Immunity and Inflammation (3Is) and Post Graduate Convenor for the 3Is. She has published over100 papers/invited reviews and has an H factor of 34.

Research interests

Prof Barnett research interests focus on identifying strategies for CNS repair particularly on cell transplantation. She is an expert on olfactory glial biology and has shown they can myelinate axons and have a neuroprotective effect in models of SCI. She is interested in how cells myelinate and how to regulate the scarring induced after CNS injury by focusing on astrocyte biology.  Recent questions are how to promote repair in CNS injury and disease using glia or stem cell transplantation and combined strategies. Can modulation of the sulphation levels around a lesion promote neurite outgrowth and myelination as well as decreasing the astrocytic sca.  Recently she has been focussing on the repair potential of mesenchymal stem cells isolated from human biopsies of olfactory mucosa.

Francisco Javier Rodríguez, PhD in Biology by the UAB, Spain (1999). Currently Group Leader at the National Hospital of Paraplegics (HNP) of the Regional Health System of Castilla-La Mancha (Toledo, Spain).

Brief Description of the Institution (HNP)

The National Hospital for Paraplegics (Hospital Nacional de Parapléjicos; HNP), established in 1974, is the biggest Spanish centre dedicated to the rehabilitation of patients with spinal cord disease. It is a state-owned hospital financed by public money. The hospital receives more than two-hundred new cases of spinal cord injured patients each year, the fourth part of the produced in whole Spain. The Hospital Nacional de Parapléjicos is a University Hospital associated to the Universidad de Castilla La Mancha (School of Medicine). In 2002, the Hospital Nacional de Parapléjicos started a department dedicated to basic, clinical and translational research: the Experimental Neurology Department (END). The END started with few research groups and now incorporates ten research groups focused on the study of neurosciences. Given the focus of the hospital, the groups that are based there have been selected on the basis of their research capability and their interests in the areas that are relevant to neural repair, neuroplasticity, motor and sensory systems and pain research. The END is an example of international (more than ten different European and non-European nationalities are represented in the staff) and multidisciplinary approach to research. Since 2003, the “Fundación Hospital de Parapléjicos” (FUHNPAIIN) constitutes the branch of the Hospital dedicated to the management of the scientific resources.

Brief Description of the Molecular Neurology Group

The Group of Molecular Neurology was created in 2005 with the incorporation of Dr. F.J. Rodríguez to the incipient END of The National Hospital of Paraplegics, with the objective of leading a research line addressed to develop combined therapies based on drugs, cell transplantation and gene therapy for neuroprotection and repair of spinal cord injuries (SCI). This broad experimental approach was based on a strong background on neural repair acquired along his PhD stage at The Group of Neuroplasticity and Regeneration from Dr. Xavier Navarro (Universitat Autonoma of Barcelona, Spain), and Postdoctoral stage at The Molecular Neurobiology Laboratory from Dr. Ernest Arenas (Karolinska Institute, Sweden), with a main focus on cell therapy, gene therapy and neural interfaces for stimulation and recording. From 2005, the major effort has been invested in obtaining Local and National Grants, the purchase and setting of research equipment, the recruitment and training of technicians, predoctoral and postdoctoral researchers, and finally setting up the wide spectrum of techniques required to face a preclinical spinal cord injury research. This effort has allowed the consolidation of a multidisciplinary group capable to face a SCI research project from its molecular aspects (mRNA and protein) to its correlation on motor and sensory functional outcome (BBB, Catwalk, Hargreaves, Von-Frey, Electrophysiology) and histology (Inflammation, Glial reactivity, Neural cell preservation and Neural tracing). At the level of results, the Group of Molecular Neurology is currently emerging with 3 articles in press (Stem Cells and PLoS One), 3 under revision (PLOS One and Journal of Neurotrauma), 5 in preparation (PLOS One; Neurobiology of Disease and Experimental Neurology) and 4 at their final experimental stage. In this context, our past and current research lines include:

• In vitro, in adult spinal cord pure and mixed neuronal-glial primary cell cultures, and in vivo, in a contusion or section injury model of SCI, assessment of drugs administered alone or in combination addressed to neuroprotect and promote axonal growth, such as minocycline, rolipram, lithium, ibuprofen, leptin and pioglitazone.
• Primary cell culture, lentiviral transduction, Fluorescent-Activated Cell Sorting (FACS) and grafting of adult neural stem cells, olfactory ensheathing glia and mesenchymal stem cells. In this regard, we are continuously developing lentiviral vectors for constitutive or conditional expression of neural tracers or growth factors such as Wnts, BDNF and Neurotrophin-3.
• Primary cell culture of adult rat spinal cord and olfactory bulb neural stem cells. Identification and in vitro assessment of new epigenetic factors for neuronal instruction, neuroprotection and axonal growth promotion, such as the Wnt family of proteins.

 

BRIEF PROFILE OF THE GROUP LEADER

 

Education / Training

Institution / Location	Degree	Years	Field of study
Univ Autonoma Barcelona (UAB, Spain)	Graduate	1987-1992	Biology
UAB (Dept. of Biochemistry; Faculty of Medicine)	Master	1992-1994	Biochemistry and Molecular Biology
UAB (Dept. of Cell Biology, Physiology and Immunology; Faculty of Medicine)	PhD	1994-1999	Physiology

 

Positions and Employment

Years	Position	Institution / Location
1999-2003	Postdoctoral (STINT and Individual Marie Curie Fellowships)	Unit of Molecular Neurobiology; Dept. of Medical Biochemistry and Biophysics; Karolinska Institute; Sweden.
2003-2005	Postdoctoral	UAB; Dept. of Cell Biology, Physiology and Immunology; Faculty of Medicine; Spain.
2005-2011	Young Group Leader	Hospital Nacional de Paraplégicos (HNP); Spain.

 

Honors and Awards

Years	Award	Institution / Location
1996	VIth grant to best project	Catalonian Society of Neurology – Uriach Foundation.
1998	Prize to best project in Multiple Sclerosis.	Schering-Plough
1999	IXth Grant to best project	Catalonian Society of Neurology – Uriach Foundation
2000	Prize Josep Trueta.	Medical Sciences Academy of Catalonia and Balears.

 

SELECTED PUBLICATIONS OF THE GROUP

1. Decimo I, Bifari F, Rodríguez FJ et al. “Nestin- and DCX-Positive Cells Reside in Adult Spinal Cord Meninges and Participate to Injury-Induced Parenchymal Reaction”. Stem Cells (In Press, DOI: 10.1002/stem.766).
2. Fernandez-Martos CM, Gonzalez-Fernandez C, Gonzalez P, Maqueda A, Arenas A, Rodriguez FJ. “Differential expression of Wnts after Spinal Cord Contusion Injury in adult rats.” PLoS One (In Press, DOI:10.1371/journal.pone.0027000).
3. Fernandez-Martos CM, Gonzalez P, Rodriguez FJ. “Acute Leptin Treatment Enhances Functional Recovery after Spinal Cord Injury.” PLoS One. 2012;7(4):e35594. Epub 2012 Apr 20.
4. Gonzalez P, Fernandez-Martos CM, Rodriguez FJ. “Ryk Receptor Is Expressed in Fibroblasts and Glial Cells, and it Modulates their Response to Spinal Cord Injury.” Journal of Neurotrauma (Manuscript Submitted).
5. González-Fernández C, Fernández-Martos CM, González P, Maqueda A, Rodríguez FJ. “Expression analysis of the Wnt family of proteins after spinal cord injury in adult mice.” PloS One (Manuscript Submitted).
6. Gonzalez P, Fernandez-Martos CM, Gonzalez-Fernandez C, Arenas E, Rodriguez FJ. “Spatio-Temporal Expression Pattern of Frizzled Receptors after Contusive Spinal 1 Cord Injury in Adult Rats”. PLoS One (Manuscript Submitted).
7. Fernández-Martos CM, González P, Vazquez S, Fernández E, Rodríguez FJ. “Acute ibuprofen anti-inflammatory and neuroprotective action promotes a significant functional recovery after spinal cord injury in adult rats.” Neurobiology of Disease (Manuscript In preparation).
8. Fernández-Martos CM, Maqueda A, Shields SD, Fernández-Núñez E, Rodríguez FJ. “Combined Minocycline and Rolipram treatment improves neuroprotection and functional recovery after spinal cord injury”. Experimental Neurology (Manuscript In preparation).
9. Shields SD, González-Fernández C, Rodríguez FJ. “Wnt signaling is constitutively active in adult spinal dorsal horn neurons and is altered after spinal cord injury”. PLoS One (Manuscript In preparation).
10. Maqueda A, Arenas E, Rodríguez FJ. “Grafting of Wnt1-overexpressing c17.2 Neural Stem Cells improves locomotor function after contusion spinal cord injury in rats”. Neurobiology of Disease (Manuscript in preparation).
11. Maqueda A, Arenas E, Rodríguez FJ. “Wnt5a-overexpressing c17.2 Neural Precursor transplantation increases myelin loss and glial reactivity with functional recovery impairment in a rat model of spinal cord contusion.”. Neurobiology of Disease (Manuscript in preparation).

 

SELECTED PUBLICATIONS OF THE GROUP LEADER

1. Navarro X, Rodriguez FJ, Labrador RO, Butí M, Ceballos D, Cuadras J, Perego G. “Peripheral nerve regeneration through bioresorbable and durable nerve guides”. 1996. J Peripher Nerv Syst, 1:53-64.
2. Navarro X, Valero A, Gudiño G, Forés J, Rodríguez FJ, Verdú E, Pascual R, Cuadra J, Nieto-Sampedro M. “Ensheathing glia transplants promote dorsal root regeneration and spinal reflex restitution after multiple lumbar rhizotomy”. 1999. Annals of Neurology, 45: 207-215.
3. Rodríguez FJ, Gómez N, Labrador RO, Butí M, Ceballos D, Cuadras J, Verdú E, Navarro X. “Improvement of regeneration with predegenerated nerve transplants in silicone chambers”. Restor Neurol Neurosci, 14: 65-79.
4. Rodríguez FJ, Gómez N, Perego G, Navarro X. “Highly permeable polylactide-caprolactine nerve guides enhance peripheral nerve regeneration through long gaps”. Biomaterials, 20: 1489-1500.
5. Verdú E, Navarro X, Gudiño-Cabrera G, Rodríguez FJ, Ceballos D, Valero A, Nieto-Sampedro M. “Olfactory bulb ensheathing cells enhance peripheral nerve regeneration”. Neuroreport, 10: 1097-1101.
6. Rodríguez FJ, Verdú E, Ceballos D, Navarro X. “Nerve guides seeded with autologous Schwann cells improve nerve regeneration”. Experimental Neurology, 161: 571-584.
7. Verdu E, Rodríguez FJ, Gudiño-Cabrera G, Nieto-Sampedro M, Navarro X. “Expansion of adult Schwann cells from mouse predegenerated peripheral nerves”. J Neurosci Meth, 99:111-117.
8. Akerud P, Holm PC, Castelo-Branco G, Sousa K, Rodríguez FJ, Arenas E. “Perspehin-overexpressing neural stem cells regulate the function of nigral dopaminergic neurons and prevent their degeneration in a model of Parkinson’s disease”. Mol Cell Neurosci, 21 (2): 205-222.
9. Holm P, Rodríguez FJ, Kresse A, Canals JM, Silos-Santiago I, Arenas E. “Critical role of TrkB ligands in the survival and phenotypic differentiation of developing locus coeruleus noradrenergic neurons”. Development, 2003, 130 (15): 3535-3545.
10. Castelo-Branco G*, Wagner J*, Rodríguez FJ*, Kele J, Sousa K, Rawal N, Pasolli HA, Fuchs E, Kitajewski J, Arenas E. *Co-primeros autores. “Differential regulation of midbrain dopaminergic neuron development by Wnt-1, Wnt-3a and Wnt-5a”. Proc Natl Acad Sci, 100 (22): 12747-52.
11. Navarro X, Rodríguez FJ, Ceballos D, Verdú E. “Engineering an artificial nerve graft for the repair of severe nerve injuries”. Med Biol Eng Comput, 41(2): 220-27.
12. Wallen-Mackenzie A, Mata De Urquiza A, Rodriguez FJ, etersson S, Friling S, Wagner J, Ordentlich P, Lengqvist J, Heyman RA, Arenas E, Perlmann T. “Nurr1-RXR heterodimers mediate RXR ligand-induced signaling in neuronal cells”. Genes and Development, 17(24): 3036-47.
13. Udina E, Rodriguez FJ, Verdu E, Espejo M, Gold BG, Navarro X. “FK506 enhances nerve regeneration of long gaps repaired with collagen guides seeded with allogeneic Schwann cells”. Glia, 47: 120-29.
14. Rodríguez FJ, Valero-Cabré A, Navarro X. “Regeneration and functional recovery following peripheral nerve injury”. Drug Discovery Today: Disease Models, 1(2): 177-185.
15. Lago N, Ceballos D, Rodríguez FJ, Stieglitz T, Navarro X. “Long term assessment of axonal regeneration through polyimide regenerative electrodes to interface the peripheral nerve”. Biomaterials, 26(14):2021-31.
16. Holm PC, Rodríguez FJ, Kele J, Castelo-Branco G, Kitajewski J, Arenas E. “BMPs, FGF8 and Wnts regulate the differentiation of locus coeruleus noradrenergic neuronal precursors”. Journal of Neurochemistry, 99(1): 343-352.
17. Lago N, Rodríguez FJ, Jaramillo J, Navarro X. “Effects of motor and sensory nerve transplants on amount and specificity of sciatic nerve regeneration”. Journal of Neuroscience Research, 85(12): 2800-2812.

Dr. Tator graduated from the Faculty of Medicine at The University of Toronto in 1961. He performed graduate studies in Neuropathology from 1961 – 1965 receiving his Masters and Ph.D. Degrees from the University of Toronto before entering the Neurosurgery Training program in 1965. He became a Fellow of the Royal College of Physicians and Surgeons of Canada in 1969. Dr. Tator joined the Neurosurgical Staff at Sunnybrook Medical Centre in 1969. Having served as Neurosurgeon-in-Chief at Sunnybrook from 1974-1984, Dr. Tator moved to The Toronto Western Hospital where he became Neurosurgeon-in-Chief from 1985-1988. He was appointed Chairman of the Division of Neurosurgery at the University of Toronto for a 10 year term beginning 1989. He is currently Professor in the Department of Surgery at The University of Toronto. His main clinical interests are in the neurosurgery of spinal diseases and acoustic neuromas. His research laboratory is dedicated to the study of acute spinal injury models.

 

Research Interests

Acute Spinal Cord and Brain Injury: In the Clinical Setting and in the Experimental Laboratory

The clinical research involves studies of acute management of traumatic spinal cord injury, ischemic lesions and demyelinating lesions and brain injuries especially the concussion spectrum of disorders. I am a principal investigator in the Christopher Reeve Foundation program »North American Clinical Trial Network.» NACTN is investigating new clinical treatments for patients with spinal cord injury, and I am a member of this organization’s consortium and board.

I am the Project Director of the Canadian Sports Concussion Project at the Krembil Neuroscience Centre, Toronto Western Hospital. The Canadian Sports Concussion Project is conducting several research studies on concussion disorders, funded by the Ontario Brain Institute.

New treatment methods are being examined as part of national and international clinical trials. My studies also involve the epidemiology of sports and recreational injuries to the brain and spine, and research into the effectiveness of injury prevention programs. These are performed as part of ThinkFirst, Canada, and now Parachute Canada.

In the field of experimental spinal cord injury, I have developed several models of acute compression injury of the spinal cord and several quantifiable outcome measures. Various blood flow and angiographic techniques have been used to study post-traumatic ischemia.

I have examined the endogenous and transplanted stem/progenitor cells in the spinal cord. A variety of neurotrophic factors and other agents have been examined in rodent spinal cord injury.

We have studied the survival, migration and differentiation of endogenous and transplanted adult rat spinal cord ependymal region stem/progenitor cells generated in vitro from neurospheres. We have shown the effects of transplantation of these cells in the adult rodent spinal cord. We are also examining a number of bioengineering strategies involving guidance channels and drug delivery systems for axonal regeneration.

Recently, we have accomplished the culturing and transplantation of human adult spinal cord derived stem cells into rats with spinal cord injury.

 

Additional Appointments

– Part of the Krembil Neuroscience Centre

– Canadian Paraplegic Association Spinal Cord Injury Research Laboratory

– SCINET Group (CIHR)

– Section Editor, Journal of Neurotrauma

 

Selected Publications

 – Tator CH, Hashimoto R, Raich A, Norvell D, Fehlings MG, Harrop JS, Guest J, Aarabi B, Grossman RG. Translational potential of preclinical trials of neuroprotection through pharmacotherapy for spinal cord injury. J Neurosurg Spine. 17(1 Suppl): 157-229, 2012.

– Mothe AJ, Zahir T, Santaguida C, Cook D, Tator CH. Neural stem/progenitor cells from the adult human spinal cord are multipotent and self-renewing and differentiate after transplantation. PLoS One. 6(11):e27079, 2011.

– Kang CE, Baumann MD, Tator CH, Shoichet MS. Localized and sustained delivery of fibroblast growth factor-2 from a nanoparticle-hydrogel composite for treatment of spinal cord injury. Cells Tissues Organs. 197:55-63, 2013

– Tator CH. Sport concussion education and prevention. Journal of Clinical Sport Psychology, 6:293-301, 2012.

– Nomura H, Kim H, Mothe A, Zahir T, Kulbatski I, Morshead CM, Shoichet MS, Tator CH. Endogenous radial glial cells support regenerating axons after spinal cord transection. Neuroreport. 21(13):871-6, 2010.

 Professor, ICORD (International Collaboration On Repair Discoveries)
University of British Columbia and Vancouver Coastal Health
℅ Blusson Spinal Cord Centre
Vancouver General Hospital

Research Interests

After a long career in basic science research, Dr. Steeves has turned his attention to translational research, making application of research to patients a higher priority. His current research focuses on arm and hand rehabilitation after spinal cord injuries. His goal is to improve rehabilitation strategies by using assistive robots and virtual-reality training. With a number of colleagues from across the globe, Dr. Steeves also works on developing better criteria for enrolling participants in SCI clinical trials, and on improving outcome measures of the electrical properties of the body and the nervous system. Better measurements of the outcomes of clinical trials can establish how well they help people with SCI, and therefore promote better recovery.

Dr. Steeves is currently a Professor in the Department of Neuroscience at the University of British Columbia and a Principal Investigator at ICORD. He was also the Founding Director of ICORD. He is the Chair of SCOPE (Spinal Cord Outcomes Partnership Endeavor). He obtained his B.Sc. and Ph.D. at the University of Manitoba. He completed his Post-Doctoral Fellowship at the University of Alberta.

Clinical trials are used to determine whether a therapy is beneficial or not. This can only be known for certain when the trials are run correctly. The improved protocols and outcome measures which result from Dr. Steeves’ work will make sure that the trials do run correctly and will improve their validity. This will allow potential therapies and interventions to be accurately assessed as beneficial or not. And whether a treatment is beneficial or not is extremely important to recovery!

As the founding director of ICORD, Dr. Steeves says the greatest reward of working at ICORD is watching its continued evolution. He especially enjoys the recognition received by the investigators and trainees of ICORD from the international research community. Watching the research centre continue to succeed is a great feeling for someone involved since the start.

Recent Collaborations

Dr. Steeves is the Chair of SCOPE (Spinal Cord Outcomes Partnership Endeavor) which works on translating discoveries to clinical trials.

He also collaborates with EMSCI (European Multicenter Study about Spinal Cord Injury) to analyse the database on SCI patients and their injuries to determine better clinical trial protocols.

Major Findings:

Dr. Steeves’ research has shown how neural pathways from the brainstem to the spinal cord are essential in many species to initiate locomotion. This also established their fundamental role in activating and controlling movement.

Dr. Steeves helped discover that, although myelin in the brain and spinal cord helps neurons function more efficiently by wrapping around them, it also inhibits healing when the neurons are injured.

Dr. Steeves’ recent research has helped to establish guidelines for clinical trials on SCI.

Techniques employed in the lab

• Electrophysiological recordings (electrical and contact heat evoked potentials)
• Robot assisted movement
• Virtual reality training

Affiliation with organizations and societies

• Board of Directors, American Spinal Injury Association (ASIA)
• Board of Directors, Asia-Pacific Symposium on Neural Regeneration
• Scientific Program Committee, International Spinal Cord Society (ISCoS)
• Board of Directors, International Symposium on Neural Regeneration (ISNR)
• Chair, Spinal Cord Outcomes Partnership Endeavor (SCOPE)

Awards

Some of Dr. Steeves’ recent major awards and accomplishments include:

• Champion of Change Award (National Spinal Cord Injury Conference, 2012)
• Peter Wall Distinguished Scholar in Residence (2011-2012)
• John & Penny Ryan BC Leadership Chair (2002-2010)