The Spinal Cord Meeting ISCORE’15 organized by the Step by Step foundation aims to bring together high profile international speakers consist of leading experts clinicians, clinical scientists and molecular biologists of international prestige in areas which have already entered, or are expected to enter shortly, in experimental therapeutic trials in patients. A major goal of The Spinal Cord Meeting ISCORE’15 in advancing the translation of research data to the clinic is to promote multi-pronged approaches for therapy of this complex problem.
The objective is for the speakers to report their progresses as well as to promote dialogue with the other researchers.
Leif A. Havton, M.D., Ph.D.
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.
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.
– 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)
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
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)
Invited Book Chapters and Reviews (past 10 years)
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, 2nd 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.
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:
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 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.
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
|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
|The Ohio State University||Research Scientist||1999||Neuroimmunology and SCI|
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.
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
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)
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.
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.
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.
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.
Complete List of my published work: http://www.ncbi.nlm.nih.gov/pubmed/?term=Popovich-P
Ongoing Research Support
R01NS083942 Popovich (PI) 09/30/2014-10/01/2019
Preventing autonomic dysreflexia to promote immune function after spinal cord injury
R01 NS047175 Popovich (PI) 02/15/09-01/31/14 [no-cost extension through 01/16]
Lymphocyte functions in the injured spinal cord
R01 AG033028 Godbout (PI) 09/31/09-08/31/14 [no-cost extension through 08/15]
Aging, microglia dysregulation and depression
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
OSU2013 20012207 McTigue (PI) 01/01/14-12/31/18
Spinal Cord Injury Training Program
R01 NS082095 McTigue (PI) 08/01/13-07/31/18
Restoring iron homeostasis to promote recovery after spinal cord injury
W81XWH-13-1-0356 Popovich (PI) 09/30/13-09/29/16
Reversing maladaptive plasticity to cure autonomic dysreflexia after spinal cord injury
R01 NS043246 McTigue (PI) 07/01/11-06/30/16
Axons and the extracellular matrix in spinal cord injury
R21 NS081413 Popovich (PI) 09/01/12-08/31/14 [no-cost extension through 08/15]
miRNA regulation of macrophage after spinal cord injury
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.
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.
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:
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
SELECTED PUBLICATIONS OF THE GROUP LEADER
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.
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.
– Part of the Krembil Neuroscience Centre
– Canadian Paraplegic Association Spinal Cord Injury Research Laboratory
– SCINET Group (CIHR)
– Section Editor, Journal of Neurotrauma
– 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.
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.
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.
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
Affiliation with organizations and societies
Some of Dr. Steeves’ recent major awards and accomplishments include: