These are the ISCORE 2019 Speakers
The Spinal Cord Meeting ISCORE’19 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’19 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.
School Health Sciences Center for Neural Repair
The work of the Spinal Cord Injury Group at the Center for Neural Repair focuses on augmenting regeneration of the adult spinal cord after injury. The injured spinal cord does not regenerate because: 1) cellular “bridges” that can support axonal regeneration do not naturally form in an SCI lesion site; 2) growth factors are not produced in the injured spinal cord to stimulate regeneration; 3) injured CNS neurons do not fully express a “growth program” to recruit new regeneration; and 4) the environment of the injured adult spinal cord inhibits regeneration due to the presence of inhibitory extracellular matrix molecules that form around the injury site, and due to the presence of inhibitory proteins on adult myelin that block regeneration.
Neural stem cells exist in an intrinsically high growth state. When grafted to sites of spinal cord injury, neural stem cells survive and extend up to hundreds of thousands of axons into the injured spinal cord (Lu et al, Cell 2012; Lu et al, Neuron 2014; Kadoya et al, Nature Medicine 2016; Lu et al, J Clin Invest 2017; Poplawski et al, Science Trans Med 2017; Dulin et al, Nature Comm 2018; Rosenzweig et al, Nature Medicine 2018). Injured adult axons regenerate into neural stem cell grafts and form synapses; in turn, axons extending from grafts to the host spinal cord below the lesion site also form synapses onto host neurons. New neural relay circuits are formed that support partial functional improvement.
Building on this biology, our current research efforts are focused on a range of topics from basic discovery of genes that enable host axon regeneration, to late stage translational primate studies that are leading up to human translation. Our experimental techniques include genomic and epigenomic studies, cell biology, proteomics, bioinformatics, in vitro assays, in vivo models of SCI in rodents and primates, electrophysiology and behavior.
We are also using tools of bioengineering, nanotechnology and 3D printing to enhance and guide regenerating axons in the injured spinal cord and peripheral nerve.
Last publications related to Spinal Cord Injury
Kumamaru H, Lu P, Rosenzweig ES, Kadoya K, Tuszynski MH.
Cell Rep. 2019 Feb 26;26(9):2329-2339.e4. doi: 10.1016/j.celrep.2019.01.099.
Lien BV, Tuszynski MH, Lu P.
Exp Neurol. 2019 Apr;314:46-57. doi: 10.1016/j.expneurol.2019.01.006. Epub 2019 Jan 15.
Koffler J, Zhu W, Qu X, Platoshyn O, Dulin JN, Brock J, Graham L, Lu P, Sakamoto J, Marsala M, Chen S, Tuszynski MH.
Nat Med. 2019 Feb;25(2):263-269. doi: 10.1038/s41591-018-0296-z. Epub 2019 Jan 14.
Kumamaru H, Lu P, Rosenzweig ES, Tuszynski MH.
Stem Cell Reports. 2018 Oct 9;11(4):861-868. doi: 10.1016/j.stemcr.2018.08.009. Epub 2018 Sep 6.
Poplawski GHD, Lie R, Hunt M, Kumamaru H, Kawaguchi R, Lu P, Schäfer MKE, Woodruff G, Robinson J, Canete P, Dulin JN, Geoffroy CG, Menzel L, Zheng B, Coppola G, Tuszynski MH.
Sci Transl Med. 2018 May 23;10(442). pii: eaal2563. doi: 10.1126/scitranslmed.aal2563.
Rosenzweig ES, Brock JH, Lu P, Kumamaru H, Salegio EA, Kadoya K, Weber JL, Liang JJ, Moseanko R, Hawbecker S, Huie JR, Havton LA, Nout-Lomas YS, Ferguson AR, Beattie MS, Bresnahan JC, Tuszynski MH.
Nat Med. 2018 May;24(4):484-490. doi: 10.1038/nm.4502. Epub 2018 Feb 26.
Brock JH, Graham L, Staufenberg E, Im S, Tuszynski MH.
J Neurotrauma. 2018 May 1;35(9):1069-1078. doi: 10.1089/n
Dr. Bo Chen
Dr. Bo Chen
Department of Neuroscience, Cell Biology, & Anatomy
University of Texas Medical Branch
Axonal Growth and Degeneration, Neuro-degeneration/protection, Neuronal Regeneration, Neuroscience
PhD, University of Miami
Postdoc, Harvard Medical School
Neural Degeneration and Regeneration in the Mammalian Retina
We are currently recruiting motivated postdoctoral researchers and students to join our research adventures. The main research interests of my laboratory focus on the mechanistic and therapeutic studies of neurodegenerative diseases in the retina resulting in vision impairment and blindness. We study signaling pathways and gene expression network in retinal neurons in normal and diseased conditions, with an ultimate aim to save vision. Neuroprotection and neuroregeneration are the two main strategies we use to prevent the death of existing neurons or to generate new neurons. 1. For neuroprotection, we investigate molecular mechanisms underlying the degeneration of photoreceptors, the primary sensory neurons that mediate the first step in vision, and ganglion cells, the output neurons of the retina. An in-depth understanding the signaling pathways that are perturbed in a diseased retina will facilitate the design of therapeutic strategies to protect photoreceptors and ganglion cells through modulation of the components of the affected pathways. 2. For neural regeneration, we examine the intrinsic signaling pathways and transcription control in Müller glial cells, the primary glial cell type in the retina, in order to reprogram them in vivo to generate adult retinal stem cells that are capable of differentiating to retinal neurons. 3. In addition, my laboratory is also actively exploring strategies to promote axon regeneration using optic nerve crush to model CNS (central nervous system) injury.
Dr. Simone Di Giovanni
Dr. Simone Di Giovanni
Imperial College. London
Faculty of Medicine, Department of Medicine
Chair in Restorative Neuroscience
I hold a Chair in Restorative Neuroscience at Imperial College where my research group investigates the molecular signalling and transcriptional mechanisms that control axonal sprouting and regeneration. I also hold a honorary post within the NHS as a consultant in Neurology. Previously, since 2006, I worked at the University of Tuebingen, Germany as a Research Group Leader, where I was also a consultant clinician in Stroke and General Neurology.
I did my post-doctoral training in Neuroscience studying gene expression regulation after spinal cord injury at Georgetown University, Washington DC, 2001-2004 where I became research Instructor (2004-2006). I studied Medicine at La Sapienza University and did my Neurology training at Catholic University, Rome, Italy.
Research in my group aims to investigate the molecular signalling mechanisms that discriminate between axonal regeneration and regenerative failure including following peripheral and spinal cord injuries respectively. In fact, while axons that lie in the periphery mount a regenerative programme, axons in the central nervous system do not. Therefore we prioritize the study of the post-injury differential regenerative ability of dorsal root ganglia neurons. They are pseudounipolar sensory neurons that from the same cell body project a peripheral regeneration-competent axon to the periphery and a central regeneration-incompetent axon into the dorsal column of the spinal cord.
Since axonal regeneration in the peripheral nervous system is imperfect and inefficient, enhancing the regenerative properties of the injured central nervous system such as in the spinal cord may be important to promote recovery of function and limit neurological disability in both spinal cord and peripheral nerve injury. Our work can have broad implications for conditions spanning from traumatic, vascular, inflammatory, degenerative and metabolic (such as diabetes) damage to the spinal cord, spinal roots and peripheral nerves.
Di Giovanni S, PP4-dependent HDAC3 dephosphorylation discriminates between axonal regeneration and regenerative failure, Embo Journal, ISSN:0261-4189
Di Giovanni S, Cbp-dependent histone acetylation mediates axon regeneration induced by environmental enrichment after spinal cord injury in rodents, Science Translational Medicine, ISSN:1946-6234
Hutson TH, Kathe C, Palmisano I, et al., 2019, Cbp-dependent histone acetylation mediates axon regeneration induced by environmental enrichment in rodent spinal cord injury models, Science Translational Medicine, Vol:11, ISSN:1946-6234
Hervera A, Santos CX, De Virgiliis F, et al., 2019, Paracrine Mechanisms of Redox Signalling for Postmitotic Cell and Tissue Regeneration., Trends Cell Biol
Hervera A, De Virgiliis F, Palmisano I, et al., 2018, Reactive oxygen species regulate axonal regeneration through the release of exosomal NADPH oxidase 2 complexes into injured axons (vol 20, pg 307, 2018), Nature Cell Biology, Vol:20, ISSN:1465-7392, Pages:1098-1098
University of Miami
Dr. Levi is a tenured Professor and Chair of Neurosurgery at the University of Miami MILLER School of Medicine. He has a very busy clinical practice that focuses on complex spinal cord, spine and peripheral nerve disorders. He has been at the University of Miami for the last 25 years including completing a PhD in neurosciences. He graduated from the University of Ottawa medical school and completed his residency at the University of Toronto, as well as a spine fellowship at the Barrow Neurological Institute in Phoenix. He has served as national director of the AANS Oral Board course for the last 12 years. He is an elected member of two of our most prestigious neurosurgical societies – the American Academy of Neurosurgery and the Senior Society of Neurological surgeons.
His clinical research interests have focused on developing cellular transplantation strategies to repair injuries within both the human central and peripheral nervous system. His current research interests involve serving as (1) PI on intravascular hypothermia after human cervical spinal cord injury (2) co-PI on the FDA approved trial of “The Safety of Autologous Human Schwann Cells in Subjects with a. Sub-acute Spinal Cord Injury (SCI)” and b. chronic SCI (3) Site PI of a Phase II Proof-of-Concept Study of the Safety and Efficacy of HuCNS-Stem Cell Transplantation in Cervical SCI (4) PI on the clinical development and characterization of the use of autologous human Schwann cells for peripheral nerve injuries with a lengthy gap
Hypothermia for Spinal cord injury
- Dididze M, Green BA, Dietrich WD, Vanni S, Wang MY, Levi AD: Systemic Hypothermia in Acute Cervical Spinal Cord Injury – A Case Controlled Study. Spinal Cord. 51(5):395-400, 2012
- Madhavan, K, Benglis D, Wang M, Vanni S, Lebwohl N, Green BA, Levi AD: The use of modest systemic hypothermia after iatrogenic spinal cord injury during surgery. Therapeutic Hypothermia and Temperature Management, 2:183-192, 2012
- Levi AD, Casella G, Green BA, Dietrich WD, Vanni S, Jagid J, Wang MW: Clinical outcomes using modest intravascular hypothermia after acute cervical spinal cord injury. Neurosurgery 66(4):670-677, 2010
- Levi AD, Green BA, Wang MY, Dietrich D, Brindle T, Vanni S, Casella G, El Hammady G Jagid J: The clinical application of modest hypothermia in the treatment of acute spinal cord injury. J Neurotrauma – 26(3):407-415, 2009.
Schwann cell transplantation for Spinal cord injury
- Burks JD, Gant KL, Guest JD, Jamshidi AG, Cox EM, Anderson KD, Dietrich WD, Bunge MB, Green BA, Khan A, Pearse DD, Saraf-Lavi E, Levi AD: Imaging Characteristics of Chronic Spinal Cord Injury Identified During Screening for a Cell Transplantation Clinical Trial. J Neurosurg Focus Mar 1;46(3):E8. doi: 10.3171/2018.12.FOCUS1859, PMID:30835682, 2019
- Anderson K, Guest JD, Dietrich WD, Bunge MB, Curiel R, Dididze M, Green BA, Khan A, Pearse D, Saraf-Lavi E, Widerström-Noga E, Wood PM, Levi, AD: Safety of Autologous Human Schwann Cell Transplantation in Subacute Thoracic Spinal Cord Injury. J Neurotrauma, 2017 Feb 18. doi: 10.1089/neu.2016.4895. [Epub ahead of print]; PMID 28225648
Human neural stem cell transplantation for Spinal cord injury
- Levi AD, Anderson KD Okonkwo DO, Park P, Bryce T, Shekar KN, Aarabi B, Hsieh J, Gant K: Clinical outcomes from multi-center human neural stem cell transplantation after chronic cervical spinal cord injury. J Neurotrauma doi: 10.1089/neu2018.5843/, PMID 30180779, 2018
- Levi AD, Okonkwo D, Park P, Jenkins A, Kurpad S, Parr A, Ganju A, Aarabi B, Kim D, Casha S, Fehlings MG, Harrop JS, Anderson KD, Gage A, Hsieh J, Huhn S, Curt A, Guzman R: Emerging safety of intramedullary transplantation of human neural stem cells in chronic cervical and thoracic spinal cord injury. Neurosurgery 82(4):562-575. Doi 10.1093/neuros/nyx250, 2018
- Curt A, Levi AD, Schwab JM: Premature termination of Spinal Cord Injury Cell based trials challenge translation and the Hippocratic Oath, JAMA Neurology, June 1;74(6):635-636, doi: 10.1001/jamaneurol.2017.0318. No abstract available. Erratum in: JAMA Neurol. 2017 Jun 1;74(6):747. PMID: 28437542, 2017
- Ghobrial GM, Anderson KD, Dididze M, Gant KL, Levi AD: Human Embryonic-derived Neural Stem Cell Transplantation in Chronic Cervical Spinal Cord Injury: Functional Outcomes at 12 Months in a Phase II Clinical Trial. Clinical Neurosurgery Sep 1;64 (CN_suppl_1):87-91. doi: 10.1093/neuros/nyx242. 2017
Kristin D. Zhao
Kristin D. Zhao
Mayo Clinic, Rochester, Minnesota
Senior Associate Consultant II-Research, Department of Physical Medicine & Rehabilitation
Senior Associate Consultant II-Research, Department of Physiology & Biomedical Engineering
Associate Professor of Physical Medicine and Rehabilitation
Assistant Professor of Biomedical Engineering
Ph.D. – Rehabilitation Science
University of Minnesota, Twin Cities
MA – Kinesiology (Biomechanics track)
The University of Texas at Austin
BA – Physics
The University of Texas at Austin
Kristin D. Zhao, Ph.D., uses innovative technologies, device fabrication and imaging methods to investigate pathogenesis related to the musculoskeletal system. The long-term goal of Dr. Zhao’s research team is to develop and use diagnostic tools to enable earlier diagnosis, prescribe effective interventions for individuals with disabilities and diseases, and assess outcomes.
Dr. Zhao’s team consists of physicians, nurses, therapists, engineers and administrative staff who collaborate with external and internal investigators. Fields of study included in Dr. Zhao and her colleagues’ research include radiology, neurosurgery, orthopedics, pediatrics, physiology and biomedical engineering, and physical medicine and rehabilitation. Dr. Zhao’s research focuses on the development of assistive technologies across the lifespan, as well as the integration of novel technologies to address issues such as spinal cord injury, upper limb loss, osteoarthristis and neuromuscular diseases. Additionally Dr. Zhao’s team is interested in including analyses of sex differences and alleviating health disparities while addressing important translational questions.
Organizations including the National Institutes of Health, Paralyzed Veterans of America and Department of Defense have all contributed funding to Dr. Zhao’s research. Currently, Dr. Zhao is collaborating on research with external investigators from St. Catherine University, Vanderbilt University, Italian Institute of Technology/University of Pisa and the University of Minnesota.
Calvert JS, Grahn PJ, Zhao KD, Lee KH.
Neuromodulation. 2019 Apr;22(3):244-252. doi: 10.1111/ner.12938. Epub 2019 Mar 6. Review.
Itoigawa Y, Hooke AW, Sperling JW, Steinmann SP, Zhao KD, Itoi E, An KN.
J Biomech. 2019 Mar 6;85:134-140. doi: 10.1016/j.jbiomech.2019.01.023. Epub 2019 Jan 22.
Calvert JS, Grahn PJ, Strommen JA, Lavrov IA, Beck LA, Gill ML, Linde MB, Brown DA, Van Straaten MG, Veith DD, Lopez C, Sayenko DG, Gerasimenko YP, Edgerton VR, Zhao KD, Lee KH.
J Neurotrauma. 2019 May 1;36(9):1451-1460. doi: 10.1089/neu.2018.5921. Epub 2018 Dec 15.
Akbari-Shandiz M, Lawrence RL, Ellingson AM, Johnson CP, Zhao KD, Ludewig PM.
J Biomech. 2019 Jan 3;82:375-380. doi: 10.1016/j.jbiomech.2018.09.019. Epub 2018 Sep 29.
Gill ML, Grahn PJ, Calvert JS, Linde MB, Lavrov IA, Strommen JA, Beck LA, Sayenko DG, Van Straaten MG, Drubach DI, Veith DD, Thoreson AR, Lopez C, Gerasimenko YP, Edgerton VR, Lee KH, Zhao KD.
Nat Med. 2018 Dec;24(12):1942. doi: 10.1038/s41591-018-0248-7.
Michael G. Fehlings
Michael G. Fehlings
University of Toronto
Dr. Fehlings combines an active clinical practice in complex spinal surgery with a translationally oriented research program focused on discovering novel treatments for the injured brain and spinal cord. This is reflected by the publication of over 800 peer-reviewed articles (h-index 86) chiefly in the area of central nervous system injury and complex spinal surgery. Dr. Fehlings leads a multi-disciplinary team of researchers that is examining the application of stem cells, nanotechnology and tissue engineering for CNS repair and regeneration. He is also Chair of the Advisory Committee of the AO Foundation Clinical Investigation Division and leads several international clinical research trials. In addition, Dr. Fehlings is involved in a number of exciting initiatives, including the Center for Advancing Neurotechnological Innovation to Application (CRANIA).
Dr. Fehlings has received numerous prestigious awards including the Gold Medal in Surgery from the Royal College of Physicians and Surgeons (1996), nomination to the Who’s Who list of the 1000 most influential scientists of the 21st century (2001), the Lister Award in Surgical Research (2006), the Leon Wiltse Award from the North American Spine Society for excellence in leadership and/or clinical research in spine care (2009), the Olivecrona Award (2009) — the top award internationally for neurosurgeons and neuroscientists awarded by the Nobel Institute at the Karolinska Institute in Stockholm for his important contributions in CNS injury repair and regeneration, the Reeve-Irvine Research Medal in Spinal Cord Injury (2012), the Golden Axon Leadership Award (2012), the Mac Keith Basic Science Lectureship Award for significant contributions to the basic science of cerebral palsy and childhood onset disabilities (2012), and was the Mayfield Lecturer (2012).
In 2012, Dr. Fehlings served as the 40th President of the Cervical Spine Research Society (CSRS) — the only Canadian to do so — and was honoured with the CSRS Presidential Medallion for outstanding leadership and contributions to cervical spine research. In 2013, Dr. Fehlings was honoured with the Queen Elizabeth II Diamond Jubilee Medal presented to him by the Honourable Stephen Harper, the H. Richard Winn Prize from the Society of Neurological Surgeons, the Jonas Salk Award for Scientific Achievements from the March of Dimes Canada and the Henry Farfan Award from the North American Spine Society. In 2014, Dr. Fehlings was elected to the Fellowship of the Royal Society of Canada and to the Canadian Academy of Health Sciences, and in 2016 won the Royal College of Physicians and Surgeons Mentor of the Year Award.
Last publications related with Spinal Cord Injury
Jaja B, Jiang F, Badhiwala JH, Schär RT, Kurpad SN, Grossman R, Harrop JS, Guest J, Toups E, Shaffrey C, Aarabi B, Boakye M, Fehlings MG, Wilson JR.
J Neurotrauma. 2019 Apr 22. doi: 10.1089/neu.2018.6245. [Epub ahead of print]
Early Intravenous Infusion of Mesenchymal Stromal Cells Exerts a Tissue Source Age-Dependent Beneficial Effect on Neurovascular Integrity and Neurobehavioral Recovery After Traumatic Cervical Spinal Cord Injury.
Vawda R, Badner A, Hong J, Mikhail M, Lakhani A, Dragas R, Xhima K, Barretto T, Librach CL, Fehlings MG.
Stem Cells Transl Med. 2019 Mar 26. doi: 10.1002/sctm.18-0192. [Epub ahead of print]
Badner A, Vidal PM, Hong J, Hacker J, Fehlings MG.
J Neurotrauma. 2019 Apr 24. doi: 10.1089/neu.2018.6081. [Epub ahead of print]
Khazaei M, Ahuja CS, Rodgers CE, Chan P, Fehlings MG.
Methods Mol Biol. 2019;1919:25-41. doi: 10.1007/978-1-4939-9007-8_3.
Badhiwala JH, Ahuja CS, Fehlings MG.
J Neurosurg Spine. 2018 Dec 20;30(1):1-18. doi: 10.3171/2018.9.SPINE18682. Review.
Badhiwala JH, Wilson JR, Fehlings MG.
Lancet Neurol. 2019 Jan;18(1):24-25. doi: 10.1016/S1474-4422(18)30444-7. Epub 2018 Nov 26. No abstract available.
Yousefifard M, Sarveazad A, Babahajian A, Baikpour M, Shokraneh F, Vaccaro AR, Harrop JS, Fehlings MG, Hosseini M, Rahimi-Movaghar V.
J Neurochem. 2019 May;149(3):317-330. doi: 10.1111/jnc.14637. Epub 2019 Jan 15. Review.
NERF/VIB group leader
My central research aim is to understand how animals learn to generate and control motor behavior in health and disease. In my lab, we study mechanisms of circuit assembly, function and plasticity that lead to motor learning and recovery after neurotrauma.
We use a wide variety of methods, including detailed motor kinematic assessments, mouse genetics, viral tracing and manipulation, electrophysiological and imaging techniques. This approach allows us to manipulate functions of specific neuronal populations, which in turn helps us to understand their role in sensorimotor circuit output and plasticity.
since 2016 NERF Principal Investigator
since 2016 Assistant professor at the Department of Neurosciences, KU Leuven
2010–2016 Postdoc fellow, Friedrich Miescher Institute for Biomedical Research, Switzerland
2010 PhD, University of California Los Angeles, US
2003 BS Neuroscience with High Honors, Oberlin College, Ohio, US
- Aya Takeoka, Silvia Arber, Functional local proprioceptive feedback circuits initiate and maintain locomotor recovery after spinal cord injury, Cell Reports, April 2, 2019, 2019
- Ludwig Ruder, Aya Takeoka, Silvia Arber, Long-distance descending spinal neurons ensure quadrupedal locomotor stability, Neuron, 92(5): 1063-1078, 2016
- Emanuela Basaldella, Aya Takeoka, Sigrist Markus, Silvia Arber, Multisensory signaling shapes vestibulo-motor circuit specificity, Cell 163(2), 301-312, 2015
- Aya Takeoka, Isabel Vollenweider, Grégoire Courtine, Silvia Arber, Muscle spindle feedback directs locomotor recovery and circuit reorganization after spinal cord injury, Cell, 159(7), 1626-1639, 2014
- Aya Takeoka, Devin L Jindrich, Cintia Muñoz-Quiles, Hui Zhong, Rubia van den Brand, Daniel L Pham, Matthias D Ziegler, Almudena Ramon-Cueto, Roland R Roy, V Reggie Edgerton, Patricia E Phelps, Axon regeneration can facilitate or suppress hindlimb function after olfactory ensheathing glia transplantation, Journal of Neuroscience 31 (11) 4298-4310, 2011
University College London
I graduated from the Karolinska Institute in Stockholm in 1979 with a basic medical degree – MD and a research degree-PhD. Following a “post doc” year in Montreal I returned to the Karolinska Institute to become an Assistant Professor. After completing surgical training in Stockholm and Paris, I specialised in Nerve and Plexus surgery, I was made an Associate Professor of Surgery in 1988 and then Head of the Division of Neuro-Orthopaedics at the Karolinska Hospital. I founded a Swedish National Centre for complicated nerve injuries.
I was recruited as a Consultant Orthopaedic Nerve Surgeon to the Royal National Orthopaedic Hospital, Stanmore in London 1996. I was awarded a visiting Professorship at Imperial College of Science, Technology and Medicine in 2002 and 2003 a Professorship in Nerve Surgery from University College London. In 2006 I became a Professor of Hand Surgery at the Karolinska Institute.
I have 20 years of experience as a consultant. I am a leading and internationally renowned surgeon and basic scientist that has pioneered and developed surgical treatments of complicated nerve disorders such as brachial and lumbosacral plexus . I treat severe,complicated nerve lesions and conditions.
My main activities include nerve and plexus trauma, tumours as well as entrapment disorders of nerves. I also do hand surgery.
I direct a National Centre for the surgical treatment of complicated nerve injuries including nerve plexus and associated spinal cord injuries.
I have devoted the last 30 years to basic and clinical researches to solve and develop successful methods to repair spinal cord injuries associated with nerve plexus trauma.
I have produced 12 Chapters in books, 15 Review articles and 90 peer review articles in international highly rated clinical and basic science journals. I have written one book on a surgical technique that restores function after a type of spinal cord injury. I am a reviewer for several international scientific journals.
Goncalves MB, Clarke E, Jarvis CI, Barret Kalindjian S, Pitcher T, Grist J, Hobbs C, Carlstedt T, Jack J, Brown JT, Mills M, Mumford P, Borthwick AD, Corcoran JPT.
Bioorg Med Chem Lett. 2019 Apr 15;29(8):995-1000. doi: 10.1016/j.bmcl.2019.02.011. Epub 2019 Feb 11.
Carlstedt T, James N, Risling M.
Neural Regen Res. 2017 Dec;12(12):1960-1963. doi: 10.4103/1673-5374.221145. Review.
Goncalves MB, Wu Y, Trigo D, Clarke E, Malmqvist T, Grist J, Hobbs C, Carlstedt TP, Corcoran JPT.
Neurobiol Dis. 2018 Mar;111:70-79. doi: 10.1016/j.nbd.2017.12.016. Epub 2017 Dec 20.
James ND, Angéria M, Bradbury EJ, Damberg P, McMahon SB, Risling M, Carlstedt T.
Front Neurol. 2017 Jul 24;8:358. doi: 10.3389/fneur.2017.00358. eCollection 2017.
Front Neurol. 2017 Jul 5;8:326. doi: 10.3389/fneur.2017.00326. eCollection 2017.
Professor, Department of Physiology, Graduate School of Medicine, Keio University
Chairman, Graduate School of Medicine, Keio University
Japanese physiology professor and the current dean of Keio University School of Medicine. He is also the team leader of the Laboratory for Marmoset Neural Architecture, at RIKEN Brain Science Institute.
Neural stem cells (NSCs) possess the capability for self-renewal and are multipotent, that is, they can give rise to both neurons and glial cells. Embryonic NSCs are expected as a source for transplantation therapy, and adult NSCs as a basis of noninvasive treatment of neurological disorders. However, because the fate of embryonic NSCs is generally predetermined and restricted temporally, a given embryonic NSC cannot generate all of the cell types existing in the CNS. For example, early NSCs generate neurons but not glia; later NSCs generate both types of cells, however, they cannot give rise to early-born neurons. Meanwhile, actual use of adult NSCs for regenerative medicine is a vision far from being fulfilled because of the as-yet unexplored physiology and mechanisms of adult neurogenesis.To resolve these problems, we propose to establish in-vitro culture systems, and to develop a powerful model for investigating the mechanisms underlying early CNS development. Furthermore, we are examining adult neurogenesis both anatomically and physiologically by combining comprehensive in-vitro analyses, such as DNA microarray and ChIP-sequencing, and in-vivo analyses using knockout or knock-in mice. Findings from these approaches are expected to be applicable to regenerative therapy for neurodegenerative disorders.
- Naka H, Nakamura S, Shimazaki T, Okano H. Requirement for COUP-TFI and II in the temporal specification of neural stem cells in central nervous system development. Nature Neurosci. 2008 Aug 24:11 (9): 1014-1023.
- Kaneko S, Iwanami A, Nakamura M, Kishino A, Kikuchi K, Shibata S, Okano HJ, Ikegami T, Moriya A, Konishi O, Nakayama C, Kumagai K, Kimura T, Sato Y, Goshima Y, Taniguchi M, Ito M, He Z, Toyama Y, Okano H. A selective Sema3A inhibitor enhances regenerative responses and functional recovery of the injured spinal cord. Nat Med. 2006 Dec;12(12):1380-9.
- Okada S, Nakamura M, Katoh H, Miyao T, Shimazaki T, Ishii K, Yamane J, Yoshimura A, Iwamoto Y, Toyama Y, Okano H. Conditional ablation of Stat3 or Socs3 discloses a dual role for reactive astrocytes after spinal cord injury. Nat Med. 2006 Jul;12(7):829-34.
- Nagoshi N, Shibata S, Kubota Y, Nakamura M, Nagai Y, Satoh E, Okada Y, Mabuchi Y, Katoh H, Okada S, Fukuda K, Suda T, Matsuzaki Y, Toyama Y, Okano H. Ontogeny and Multipotency of Neural Crest-Derived Stem Cells in Mouse Bone Marrow, Dorsal Root Ganglia and Whisker Pad.Cell Stem Cell 2. 2008 Apr 10:2(4):392-403.
- Sawamoto K, Wichterle H, Gonzalez-Perez O, Cholfin JA, Yamada M, Spassky N, Murcia NS, Garcia-Verdugo JM, Marin O, Rubenstein JL, Tessier-Lavigne M, Okano H, Alvarez-Buylla A. New neurons follow the flow of cerebrospinal fluid in the adult brain. Science. 2006 Feb 3;311(5761):629-32.
Drexel University College of Medicine
Michael Lane, PhD, is an Associate professor in the Department of Neurobiology & Anatomy at Drexel University College of Medicine. He leads a research team consisting of two graduate students, a postdoc and one junior faculty member (instructor).
After completing his graduate studies and early postdoctoral work in spinal cord injury (SCI) in Australia at the University of Melbourne, Dr. Lane relocated to the University of Florida to investigate the neuroplastic potential of the injured cervical spinal cord. This research focused on respiratory dysfunction and spontaneous neuroplastic recovery. In 2013, Dr. Lane moved to the Spinal Cord Research Center within Drexel University College of Medicine’s Department of Neurobiology & Anatomy to continue his research into neuroplasticity following cervical SCI. Employing a range of electrophysiological, behavioral and neuroanatomical methods, the present goal of his research team is to 1) better define the ontribution of spinal interneurons to functional and anatomical plasticity and 2) develop and test therapeutic strategies toharness the therapeutic potential of these interneurons and enhance spontaneous neuroplasticity and lasting functional recovery. Among those therapeutic approaches being tested are intraspinal cell transplantation and rehabilitative strategies.
Title: “Neural transplants to promote respiratory plasticity after spinal cord injury”
Agency: National Institutes of Health, NINDS (R01 NS104291)
Project dates: 2018-2022
Title: “Stem cell–derived spinal interneurons to repair the injured spinal cord”
Agency: The Lisa Dean Moseley Foundation
Project dates: 2017
Title: “Repair of the Chronically Injured Spinal Cord with Cell Therapy”
Agency: Wings for Life Foundation
Project dates: 2019-2021
“The neuroplastic and therapeutic potential of interneurons in the injured spinal cord”
Zholudeva LV, Qiang L, Marchenko V, Dougherty KJ, Sakiyama-Elbert SE, Lane MA
Trends in Neuroscience (invited), 41(9): 625-639 [PMID: 30017476] (2018)
“Transplantation of neural progenitors and V2a interneurons after spinal cord injury”
Zholudeva LV, Iyer N, Qiang L, Spruance VM, Randelman ML, Bezdudnaya TG, Fischer I, Sakiyama-Elbert S, Lane MA
J Neurotrauma 35(24): 2883-2903– Online [PMID: 29873284] (2018)
“Integration of transplanted neural precursors with the injured spinal cord”
Spruance VM, Zholudeva LV, Hormigo KM, Bezdudnaya T, Marchenko V, Lane MA
J Neurotrauma, 35(15): 1781-1799 [PMID: 29295654] (2018)
“Anatomical recruitment of spinal V2a interneurons into phrenic motor circuitry after high cervical spinal cord injury”
Zholudeva LV, Karliner J, Dougherty K, Lane MA
J Neurotrauma, 34(21):3058-3065 [PMID: 28548606] (2017)
Wolfson CARD, King’s College, London
Dr Corcoran has been head of the Neuroscience Drug Discovery Unit since 2008. Our interests are the role of the retinoic acid (RA) signalling pathway in the maintenance and regeneration of the CNS. To date we have two RA drugs in clinical trials. RA acts through the nuclear receptors the retinoic acid receptors (RARs) and retinoid X receptors (RXRs) of which there are three types of each α β and γ. Given that due to their transcriptional action many pathways can be stimulated it suggests that they may have a multifactorial action on signalling cascades in CNS disorders. RA has been shown to induce axonal regeneration following SCI through specific activation of RARβ. Hitherto, RARβ agonists due to poor drug-like properties have only been available as research tools. We have developed C286, an orally available RARβ agonist drug that has multifactorial reparative effects in the CNS. Using three rat models; sensory root avulsion, spinal contusion and spinal nerve ligation, we demonstrate that C286 induces axonal regeneration, modulates neuroinflammation and prevents the onset of neuropathic pain, which are pathologies associated with SCI.
In vivo C286 at doses below the no-observed-adverse-effect level (NOEL) stimulates intrinsic growth programs in the injured neurons and regulates signalling from these to the surrounding glia. This leads to a switch from non-permissive scar tissue to an axonal growth enabling glial network. By bioinformatics we have identified key regulatory pathways that are beneficially modulated by the drug after nerve injury.
The safety and tolerability of C286 are currently being tested in a first in man study (FIM). The drug is demonstrating predictable pharmacokinetics and is well tolerated at proposed therapeutic doses. We have achieved doses required for motor functional recovery based on exposure in the rat and will eventually test the drug at higher exposure levels for sensory recovery.
Biomarkers for efficacy and target engagement are also being tested. We found that both in the rat avulsion model and in humans KCL-286 plasma exposure correlates with RARβ expression in white blood cells (WBCs).
The data taken together suggests that a PIIA trial can be set-up in the near future.
Goncalves, M. B., Y. Wu, D. Trigo, E. Clarke, T. Malmqvist, J. Grist, C. Hobbs, T. P. Carlstedt and J. P. T. Corcoran (2018). “Retinoic acid synthesis by NG2 expressing cells promotes a permissive environment for axonal outgrowth.” Neurobiol Dis 111: 70-79.
Goncalves, M. B., E. Clarke, C. I. Jarvis, S. Barret Kalindjian, T. Pitcher, J. Grist, C. Hobbs, T. Carlstedt, J. Jack, J. T. Brown, M. Mills, P. Mumford, A. D. Borthwick and J. P. T. Corcoran (2019). “Discovery and lead optimisation of a potent, selective and orally bioavailable RARbeta agonist for the potential treatment of nerve injury.” Bioorg Med Chem Lett 29(8): 995-1000.
Goncalves, M. B., Y. Wu, E. Clarke, J. Grist, C. Hobbs, D. Trigo, J. Jack and J. P. T. Corcoran (2019). “Regulation of Myelination by Exosome Associated Retinoic Acid Release from NG2-Positive Cells.” J Neurosci 39(16): 3013-3027.
Trigo, D., M. B. Goncalves and J. P. T. Corcoran (2019). “The regulation of mitochondrial dynamics in neurite outgrowth by retinoic acid receptor beta signaling.” FASEB J 33(6): 7225-7235.
Goncalves, M. B., J. Moehlin, E. Clarke, J. Grist, C. Hobbs, A. M. Carr, J. Jack, M. A. Mendoza-Parra and J. P. T. Corcoran (2019). “RARbeta Agonist Drug (C286) Demonstrates Efficacy in a Pre-clinical Neuropathic Pain Model Restoring Multiple Pathways via DNA Repair Mechanisms.” iScience 20: 554-566.