Presented, “Cell Therapy in Peripheral Nerve Injury from Bench to Clinical Work” at the 2010 The International Conference of Stem Cells and Regenerative Medicine for Neurodegenerative Diseases in Taiwan.
Presented, “Translational Research in Spinal Cord Injury” at the 2010 The International Conference of Stem Cells and Regenerative Medicine for Neurodegenerative Diseases in Taiwan.
Dr. Kerr is an Associate Professor of Neurology with a joint appointment in the Department of Molecular
Microbiology and Immunology; and Cellular and Molecular Medicine. He specializes in transverse myelitis and multiple sclerosis. Dr. Kerr has established the Johns Hopkins Transverse Myelitis Center which is
the only such center in the entire world. The center utilizes the expertise of physicians and therapists from a variety of disciplines including neurology, neurosurgery, neuroradiology, rheumatology, rehabilitation medicine and urology for a comprehensive evaluation of transverse myelitis.
Dr. Kerr also has research interest in determining the cause(s) of transverse myelitis, evaluating novel markers to help prognosticate outcomes in the acute phase, and in developing novel treatments. Dr. Kerr also investigates neural stem cells as a potential tool for functional recovery in patients with transverse myelitis and motor neuron disease. He has made significant discoveries concerning the basic molecular biology of neuronal apoptosis, especially in motor neurons of the spinal cord.
Dr. Kerr’s laboratory research focuses on models of neuronal injury in the spinal cord. Using genetic and viral induced models of motoneuron injury, his laboratory has found that though there is an intrinsic abnormality within neurons, this abnormality is insufficient to induce death of that neuron. Rather, the surrounding astrocytes and microgial cells become deranged and “kill” the “at-risk” neuron. His research laboratory is now focused on elucidating the pathways involved in this killing. These findings are relevant to viral induced diseases of the CNS and to human motor neuron diseases such as ALS (amyotrophic lateral sclerosis) and SMA (spinal muscular atrophy).
Additionally, these models are utilized to examine the possibility of neuroregeneration. By transplanting a variety of human and mouse stem cells into the spinal cord, a partial restoration of function can be facilitated. The mechanisms underlying this functional recovery are varied and not completely understood. Dr. Kerr has also been interested in the endogenous response of spinal cord neural stem cells to paralysis. Interestingly, adult spinal cords DO have stem cells. Following viral-induced paralysis, they proliferate, presumably in an attempt to repopulate the spinal cord with those cells that just recently died. But it doesn’t happen: no new neurons are formed, and instead, the proliferating stem cells become shunted toward a glial fate. It is important to understand why these cells get “pushed” toward becoming glia and by modulating the fate specification of endogenous stem cells, perhaps the spinal cord can regenerate its own neurons rather than having to transplant them! This analysis will shed light on inherent biology of the spinal cord, and may have applications to human spinal cord diseases.
Dr. Kerr also directs The Johns Hopkins Project RESTORE, a multidisciplinary research and clinical collaboration emerging from The Johns Hopkins Transverse Myelitis and Multiple Sclerosis Centers to develop new diagnostic and therapeutic strategies in the treatment of neuroimmunologic disorders, such as multiple sclerosis (MS) and transverse myelitis (TM). Project RESTORE has three principle goals: to recover from acute attacks and illness; to stop progression of disease and disability; and to regenerate nerve cells and myelin.
Dr. McDonald graduated from the University of Illinois, Champaign Urbana in 1985 with Bachelor’s of Science degree, magna cum laude, in Neuroscience. From there he matriculated at the University of Michigan, Ann Arbor, where he began a combined M.D./Ph.D. program in the Medical Scientists Training Program (MSTP) that he completed in 1992. While pursuing his advanced degrees, Dr. McDonald completed a fellowship in Neurology at the Johns Hopkins University School of Medicine and served as visiting scientist at Eli Lilly and Co in Indianapolis, IN. After receiving his M.D. and his doctorate, Dr. McDonald completed an internship in preliminary medicine at St. Joseph Mercy Hospital in Ann Arbor, MI. From 1993-1996, he completed his postgraduate training in adult Neurology at St. Louis’ Barnes Hospital and Washington University School of Medicine. Following his residency, Dr. McDonald joined the Washington University faculty in the Department of Neurology as an instructor in 1997, promoted to assistant professor of Neurology at Washington University School of Medicine. He also held co-assistant professorships in the School’s Departments of Neurological Surgery and Anatomy and Neurobiology.
In 1998, Dr. McDonald was named Medical Director of the Spinal Cord Neurorehabilitative Unit at Barnes-Jewish Hospital in St. Louis and Section Head of Spinal Cord Injury Program at Washington University. There he spearheaded development of what is now a leading spinal cord injury neuralrestoration program. It was there that he developed the “activity-based restoration” (ABR) therapies designed to help patients with long-term spinal cord injuries recover sensation, movement and independence; the therapy approached publically acknowledged as producing the substantial and delayed recovery of actor/activist Christopher Reeve.Dr. McDonald joined Kennedy Kennedy Krieger Institute in 2004 in order to launch a brand-new spinal cord rehabilitation and research program with a focus on pediatric paralysis, a program that will become the only of its kind in the world. Dr. McDonald also holds a primary appointment as Associate Professor in the Department of Neurology at Johns Hopkins University School of Medicine with co-appointments in Physical Medicine and Rehabilitation and Neuroscience departments.
Dr. McDonald sits on the advisory boards of two companies, Restorative Therapies, Inc. of Baltimore, MD and BioAxone of Montreal, Canada. He is the present Chairman of the Spinal Cord Injury Research Program Advisory Board at the University of Missouri, Columbia and holds positions on the New York State SCI Research board, and the Philadelphia Shriner’s Hospital Medical Advisory Board.
Recent professional honors include being named Medical Director of the Year by insurer HealthSouth, receiving the SCI Research Inspiration Award from the Sam Schmidt Foundation and receiving the Reeve Research for Freedom Award from Gateway to a Cure.Research Summary:
Dr. McDonald’s research interests focus on the development of interventions to reduce spinal cord injury, promote remyelination, enhance regeneration and encourage recovery of function. In addition, Dr. McDonald is interested in studying the biology of embryonic stem cells, neural progenitor cells, mechanisms of oligodendrocyte death and glutamate excitotoxicity, mechanisms regulating myelination and the ontogeny of excitatory amino acid and related neurotransmitter pathways in the brain and their relationship to neurological disease.Dr. McDonald also actively leads industry multi-center clinical trials in spinal cord injury repair, having completed 6 trials to date including the first human stem cell transplantation study with the company Diacrin. In addition to the completion of an ongoing project examining the efficacy of activity-based restoration in 60 adult patients with spinal cord injuries, Dr. McDonald and his team at the International Center for Spinal Cord Injury will soon launch a large prospective multi-center trial evaluating the efficacy of these therapies in pediatric patients in collaboration with the Philadephia Shriner’s Hospital.
Dr. McDonald’s research is increasingly focusing on approaches to regeneration and restoration of function in spinal cord injury and other disorders of paralysis using activity-base therapies. Such focus includes other regenerative approaches that have the potential of being translated into human therapies in the near-term.
Spinal Cord Injury causes many changes at the molecular level that damage or destroy key components of the nervous system that carry signals to and from the brain – including neurons, axons and the myelin coating that protects the nervous system much like the insulation around an electrical cord, as well as the vascular infrastructure that carries oxygen to these tissues.
The Molecular Neurobiology Laboratory focuses on strategies to replace lost neurons, help axons regenerate, and regeneration of the myelin coating around damaged or regenerating axons. Using undifferentiated precursor cells, gene therapies, and transplanted neurons, the lab seeks to understand the development of these key components of the vascular and nervous system at the molecular and genetic level in order to protect them from damage and/or promote their regeneration.
The general research focus of my laboratory is to utilize molecular and cellular biological techniques to address repair in spinal cord injury (SCI). These studies are usually initiated in vitro and successful approaches then taken into whole animal experiments. When designing strategies to facilitate functional restoration in SCI, three issues need to be considered: 1) replacement of lost neurons, 2) remyelination of de-myelinated and/or regenerating axons, and 3) inducing axotomized descending motor and ascending sensory axons to regenerate. We are utilizing multiple strategies to examine all three issues.
Neuronal replacement requires transplantation of exogenous neurons, as CNS neurons do not regenerate. Similarly, injury-induced de-myelination is secondary to a loss of intrinsic oligodendrocytes. Our approach to re-myelination is to transplant oligodendrocyte precursors into the demyelinated area. We are using CNS-derived stem cells as a source for both neurons and oligodendrocytes. Ongoing experiments in vitro are using retroviral vectors to infect the undifferentiated precursor cells with transcription factors that direct either neuronal or oligodendrocytic differentiation. Additionally, we isolate neuronal-restricted and glial-restricted populations of precursor cells. These cells are then engrafted into specific SCI models that deplete functionally discrete populations of neurons or endogenous oligodendrocytes in specific ventral motor pathways. We utilize a battery of behavioral and electrophysiological analyses to both characterize the initial deficits and determine the degree to which functional recovery is observed.
Our attempts to engender axotomized supraspinal, propriospinal, and sensory axons to regenerate takes a two-fold approach. We again use undifferentiated stem cells and genetically engineer them to express specific neurotrophic factors and/or cell surface molecules that facilitate regeneration by providing trophic support or a permissive substrate for regeneration. In these studies, we induce the stem cells towards an astrocytic phenotype in vivo, as early differentiating astrocytes are permissive for axonal outgrowth. Concomitant with the engraftment of these cells into the injured spinal cord, we use adenoviral or lentiviral vectors to deliver specific neurotrophic molecules at specific times post-injury to the cell bodies in the brainstem and/or into the spinal cord caudal to the injury site. This should enhance the regenerative capacity of the axotomized neurons and coax the regenerating fibers to leave the graft and enter the distal cord, respectively. In the second approach, we are characterizing in the injured spinal cord and brain the expression of the eph family of receptor tyrosine kinases and their ligands the ephrins. These molecules mediate repulsive interactions between cells that express receptor and ligand. We hypothesize that the expression of ephs and ephrins in the injured spinal cord may contribute to the non-permissive environment for regeneration. We have devised a number of reagents that can block the function of these molecules and are examining their effects on regeneration of specific ascending and descending fiber populations.
We recognize that no single strategy will be by itself effective in eliciting optimal regeneration in SCI. Our ultimate goal is to combine those individual strategies of ours and our colleagues here in the Department of Neurological Surgery that are effective to design interventive approaches that will result in functionally significant improvements after SCI.
Canada Research Chair in Spinal Cord Injury
Michael Smith Foundation for Health Research Career Scholar
Associate Professor, Department of Orthopaedics, University of British Columbia
Dr. Kwon specializes in the surgical management of adult spinal disorders. Dr. Kwon earned a medical degree from Queen’s University, then completed his orthopaedic surgical residency at UBC in 2000. Following this, he did a fellowship in adult spinal surgery at the Rothman Institute at Thomas Jefferson University in Philadelphia. He also completed a PhD in Neuroscience from UBC in the study of regeneration strategies for spinal cord injuries. As a Vancouver Coastal Health Research Institute Mentored Clinician Scientist, he divides his time between patient-care at Vancouver General Hospital and research in spinal cord repair at his laboratory on the UBC campus and is currently serving at the rank of Associate Professor.
Director of Neurosurgery, Lenox Hill Hospital
Professor of Neurosurgery and Neuroscience, Mount Sinai School of Medicine
Dr. Winn joined the faculty of the Department of Neurosurgery at Mount Sinai in 2003 as Director of Research. His own interest in Neurosurgical research began in 1971: as part of the University of Virginia residency, Dr. Winn spent a year in England where he had the opportunity to initiate clinical research on the natural history of cerebral aneurysms at Atkinson Morley’s Hospital in Wimbledon and to pursue long-term outcome studies initiated by Sir Wylie McKissock.
Following military service in Germany, Dr. Winn returned to a faculty position, joining John A. Jane, M.D., Ph.D., at the University of Virginia where he initiated his clinical activities while simultaneously pursuing basic science training in cardiovascular and cerebrovascular physiology.
It was in this laboratory setting that he began his studies on the role of adenosine and cerebral blood flow regulation. He has been continuously funded by the NIH since 1974 for this ongoing effort.
From 1983-2002 Dr. Winn was Professor and Chairman of the Department of Neurological Surgery at the University of Washington in Seattle. In 2003, Dr. Winn moved to Mount Sinai Medical School where he was appointed as a tenured Professor in the Departments of Neurosurgery and Neuroscience.
He has served on the American Board of Neurological Surgery (Vice Chairman, 2001-2002) and on the Editorial Board of the Journal of Neurosurgery (Chairman, 2000-2001). He is a founding and consulting editor of Neurosurgery Clinics of North America and the editor-in-chief of Youman’s Fifth edition, The Textbook of Neurological Surgery (Elsevier, 2003) and co-editor of The Management of Cerebral Aneurysms (Elsevier, 2003). Widely recognized for his clinical expertise, he has been named a “Best Physician” in multiple publications since 1991. His clinical specialty interests are cerebrovascular diseases, tumors, spine, radiosurgery and trauma.
The Winn Prize
The H. Richard Winn, M.D. Prize is an annual award established in presented by of the Society of Neurological Surgeons to encourage research in the neurosciences and to recognize outstanding, continuous commitment to research in the neurosciences by a neurological surgeon. The Society of Neurological Surgeons is the American society of leaders in neurosurgical residency education, and is the oldest neurosurgical society in the world.