The Edward Jekkal Muscular Dystrophy Research Fellowship
PREAMBLE
The Edward Jekkal Muscular Dystrophy
Research Fellowship is designed to strengthen the training of senior postdoctoral
students or young research faculty members
interested in neuromuscular disease research. The Fellowship will generally
be awarded for a period of 2 years. Application forms are available in pdf
format or msword
format
The Fellowship is funded through the
generosity of the Muscular Dystrophy Association and the late Edward Jekkal,
an AT&T mechanical designer who
lived in Bucks County, Pennsylvania. Mr. Jekkal is remembered for his kindness
and generosity
and the talent that enabled him to design assistive devices to compensate
for disabilities.
Creation of the fellowship was furthered by Leonard S. Jacob, M.D., Ph.D.,
a MCP alumnus and who was a Board of Trustees member and a friend of the
Jekkal family. The Jekkal estate and the MDA contributed to establish the
fellowship,
with a matching contribution from Drexel University.
Drexel University will provide the training
environment that will assist the Fellow in establishing an independent multi-disciplinary
research program.
Interested applicants will be expected to work with a primary sponsor at
Drexel
University for the purpose of establishing a host laboratory and developing
the proposal. Junior research faculty at Drexel University can submit an
independent application. The typical successful candidate will already
have completed several
years of postdoctoral research training about to move into a faculty position
and can also be junior faculty. Special consideration will also be given
to M.D’s. who have completed their residency training and will be
in the position to plan and execute a research program while receiving
input
and guidance
from a core group of faculty, in addition to his/her primary sponsor. This
core training group will be drawn from faculty having demonstrated strengths
in the physiology and pathology of neuromuscular and related diseases,
molecular biology of transmitter receptors and ion channels, regulation
of contractile
activity in muscles, and the structural organization and regenerative capacity
of neurons. These faculty members represent the departments of Neurobiology
and Anatomy, Pharmacology, Neurology, Microbiology and Immunology at Drexel
University. The sponsor will be responsible for providing the primary training
and the host laboratory.
Advisory Committee
Itzhak Fischer, Ph.D., Chair
Leonard Jacob, M.D., Ph.D.
Peter Baas, Ph.D.
Anthony Burns, M.D.
Ilya Rybak, Ph.D.
Training Faculty
Elizabeth Blankenhorn, Ph.D.
Jeffrey Deitch, Ph.D.
Simon Giszter, Ph.D.
Terry Heiman-Patterson, M.D.
John Houle, Ph.D.
Michel Lemay, Ph.D.
Gordon Lutz, Ph.D.
Young Jin Son, Ph.D.
Jekkal Research Fellowship
Faculty Research Descriptions:
Elizabeth Blankenhorn, Ph.D. – Microbiology and Immunology
Projects: We are conducting several studies to examine the genetic control of susceptibility to experimental allergic encephalomyelitis (EAE), an animal model of multiple sclerosis, in mice and in rats (right). A second project is to map both EAE-susceptibility and diabetes-susceptibility loci on the LEW rat genetic background, and to understand the role of the TCR haplotypes in severity of disease. We are extending our finding that diabetes in the BB rat strain is controlled by a QTL that we discovered on chromosome 4. Positional cloning of this QTL is underway, and we were excited to discover that this gene is also critical for the development of Type I diabetes induced by exposure to a virus as well. In recent years, we have applied genetic analyses to study susceptibility to retroviral infections, to amyotrophic lateral sclerosis (ALS), and to retrovirally induced lymphomas in mice. Finally, in collaboration with the Wistar Institute, we are mapping wound healing genes in several large crosses to confirm our original mapping of six QTL associated with the trait of wound healing/regeneration, and to understand the significant sexual dimorphism in the genetic control of this trait.
Methods: Immunogenetic models in the lab include both rat and mouse models
of multiple sclerosis and diabetes, wound healing, ALS and other complex traits.
We use genetic linkage to first identify the position of the gene that regulates
that trait. The inheritance of marker alleles is compared (“linked”)
to the inheritance of the phenotype and a preliminary assignment of the location
of incidence and quantitative trait loci (QTL) is made. The QTL are confirmed
in subsequent crosses, or are fixed in the genome by selective breeding, for
the purpose of positional cloning and identification of the disease gene itself.
We typically breed animals to express the susceptible allele of the QTL only
on the resistant background, to determine if it can act in isolation to create
a phenotype related to the complex trait.
The genetic analyses are combined with traditional immunological assays to assess
immune function, and with real-time PCR and array techniques to assess gene
expression. When successful, we are able to map the disease gene, identify it,
and determine the important features of each allele that contribute to the different
manifestation of the disease state. In this way we truly define “gene?ˆ
allele?ˆ protein?ˆ function” relationships for important disease
entities.
Relevant Publications
Alexander GM, Erwin KL, Byers N, Deitch JS, Augelli BJ, Blankenhorn EP, Heiman-Patterson TD. Effect of transgene copy number on survival in the G93A SOD1 transgenic mouse model of ALS. Brain Res Mol Brain Res. 130:7-15. 2004
Polanczyk M, Yellayi S, Zamora A, Subramanian S, Tovey M, Vandenbark AA, Offner H, Zachary JF, Fillmore PD, Blankenhorn EP, Gustafsson JA, Teuscher C. Estrogen receptor-1 and -2 regulate the severity of clinical experimental allergic encephalomyelitis in male mice. Am J Pathol. 164:1915-24. 2004
Blankenhorn EP, Rodemich L, Martin-Fernandez C, Leif J, Greiner DL, Mordes JP. The rat diabetes susceptibility locus Iddm4 & at least one additional gene are required for autoimmune diabetes induced by viral infection. Diabetes 54:1233-7. 2005
Heiman-Patterson TD, Deitch JS, Blankenhorn EP, Erwin KL, Perreault MJ, Alexander BK, Byers N, Toman I, Alexander GM. Background and gender effects on survival in the TgN(SOD1-G93A)1Gur mouse model of ALS. J Neurol Sci.;236:1-7. 2005
Teuscher, C., R Noubade, K Spach, J Y. Bunn, P D. Fillmore, J F. Zachary, and
E P. Blankenhorn. Evidence That The Y-Chromosome Influences Experimental Allergic
Encephalomyelitis in Male and Female Mice. Proc Natl Acad Sci USA. 23;103(21):8024-9.
2006
Jeffrey S. Deitch, PhD – Department of Neurology
Terry Heiman Patterson, M.D. – Department of Neurology
Our lab uses a number of different approaches to study the mechanisms of motor neuron diseases and to search for potential therapeutics to degenerative diseases of the neuromuscular system.
One line of investigation uses the G93A SOD1 mouse model of amyotrophic lateral sclerosis (ALS) to look for physiological changes early on in the disease that might give clues about disease origins and progression. We have been focusing on inflammatory molecules in the spinal cord and the role of astroglia, microglia and cytokine signaling in the axial progression of the disease. In collaboration with Tim Cunningham in the Department of Neurobiology & Anatomy, we are characterizing the changes in activity and levels of soluble phospholipase A2 (sPLA2). This enzyme is one of the first molecules activated in the inflammatory signaling cascade and is increased in people with ALS above the control population. We will be testing the efficacy of sPLA2 inhibitors in changing the time course of the onset and progression of the disease in the mouse model. If successful, trials in human subjects are planned.
A second line of work uses cell culture to investigate specific degenerative processes in motor neurons. Although the causes of ALS may involve many cell types and environmental influences, it is the motor neuron that succumbs. Cell culture also provides a faster method for screening compounds for potential therapeutic effects on motor neuron survival. Cultured neurons, glia and muscle derived from control mice and transgenic mice expressing human mutant (G93A) SOD1 will be co-cultured in various combinations to test how the mutation in one cell type affects normal cells of another cell type. Each culture will be examined for the onset of indicators of neurodegeneration, such as calcium regulation, mitochondrial function and oxidative stress. Other studies examine the whether neurotrophic factor signaling mechanisms are affected by G93A SOD1 transfection in the spinal cord cells.
Finally, we are involved in a consortium of researchers attempting to map the
genetic background of G93ASOD1 mice for genes that modify the onset and progression
of disease. By breeding the transgenic mice onto different strain backgrounds,
we and others have found that survival time varies by weeks depending on strain.
For instance, mice with the G93ASOD1 transgene bred onto a pure C57Bl6 background
live almost two weeks longer than transgenic mice bred onto an SJL background.
One gene of interest as a modifier of ALS expression is the survival motor neuron
(SMN1) gene, which when mutated is a cause of spinal muscular atrophy. An SMN1
polymorphism has been identified risk factor for ALS in humans. How these two
neuromuscular diseases are related and how one may modify the other is a major
topic of investigation in the mapping studies.
Relevant Papers & Abstracts:
Deitch JS, Fischer, I. Hippocampus. In Haynes, L.W (ed.) The Neuron in Tissue Culture, IBRO Handbook Series: Methods in the Neurosciences, vol 18. Wiley:Chichester, pp 531-539 (1999).
Alexander GM, Deitch JS, Seeburger JL, Del Valle L, Heiman-Patterson TD. (2000) Elevated cortical extracellular fluid glutamate in transgenic mice expressing human mutant (G93A) Cu/Zn superoxide dismutase. J. Neurochem., 74:1666-1673.
Deitch JS, Alexander GM, Del Valle L, Heiman-Patterson TD. GLT-1 glutamate transporter levels are unchanged in mice expressing G93A human mutant SOD1. J. Neurol. Sci., 193:117-126 (2002).
Alexander GM, Erwin KL, Byers N, Deitch JS, Augelli B.J, Blankenhorn EP, Heiman-Patterson TD. Effect of transgene copy number on survival in the G93A SOD1 transgenic mouse model of ALS. Mol. Brain Res., 130:7-15 (2004).
Heiman-Patterson TD, Deitch JS, Blankenhorn EP, Erwin KL, Perreault MJ, Alexander BK, Byers N, Toman I, Alexander GM. (2005) Background and gender effects on survival in the TgN (SOD1-G93A)1Gur mouse model of ALS. J. Neurol. Sci., 236:1-7.
Heiman-Patterson TD, Deitch J, Alexander GA, Erwins K, Byers N, Toman I, Blankenhorn EP. (2005) Genetic Loci Linked to Phenotype in the G93A SOD1 Mouse. Neurology 64S:A204-05
Heiman-Patterson TD, Deitch J, Alexander GA, and Cunningham T (2005) Phospholipase A2 is implicated in the inflammatory component of injury in G93A SOD1 Transgenic Mice. Presented at the 16th International Symposium on ALS/NMD, Dublin, Ireland, Abstract # SW204.
Simon Giszter, Ph.D. – Department of Neurobiology and Anatomy
My laboratory encompasses two research approaches relevant to CNS control of the musculoskeletal plant and drives to the motoneuron.
The first approach involves basic research into the spinal cord's capabilities for organization and control of limb biomechanics. For these studies we utilize the spinal frog and more recently the decerebrate rat. The spinal frog is a robust preparation that exhibits complex reflex behaviors. These behaviors capture many of the fundamental biomechanical and control problems faced by tetrapods. Recent results obtained from microstimulation of frog spinal cords suggest there may exist a few primitives or modules for controlling force and movement during reflex behaviors and perhaps motor control generally. In these experiments we recorded the biomechanical limb responses as force-fields generated in the limb by the spinal cord. We discovered that there were a few force-field types, and that these types were stable and scaled in magnitude with increasing stimulation strength or duration. These force-field types could be combined by simple vector superposition to allow construction of novel force-fields for limb control. Early work also suggested that these primitives were located in specific regions in the spinal cord. Recent dense microstimulation maps confirm that only a few force directions are represented. Specific patterns of muscle activity can be used as predictors of the force directions. Finally, the data demonstrate that the spatial distributions of force directions elicited by microstimulation can be related to the spinal cord structure and in particular the interneuron target fields of different descending and sensory systems in the grey matter. Exploration of how these systems and their control interact in the generation and control of reflex and locomotory behaviors is the current focus of this project. We have successfully demonstrated reflex behaviors are constructed and adjusted using combinations of force-field primitives. We are now examining the neural organization underlying the premotor drives for primitives in the spinal cord.
Recovery of function following injury involves growth, reconnection of cells
and adjustment of synaptic strength. These changes cooperate to produce recovery
of system level behaviors. At the system level, function in the repaired CNS
involves adjustments of the computational tasks carried out by the nervous system.
These compensate for or utilize the alterations, deficits and mistakes in the
new information flows. From this perspective understanding of the biomechanics
and control engineering of the normal, injured and recovered systems is essential
to assess the successes and failures of clinical interventions and the behavior
of the segmental motoneuron and reflex loops in these settings. The second approach
used in my laboratory involves the examination of Brain Machine Interface and
Robotic rehabilitation of locomotion in rats. We test how these impact on spinal
and cortex organization and control in normal, neonatal transected and adult
transected spinal rats. Our research is shedding light both on normal motor
control, systems level organization, premotor drive behaviors and on what systems
coordinate recovery. The notion of motor primitives and modular premotor drives
is an organizing idea in both projects.
Relevant Publications
Giszter SF, Kargo W, Shibayama M and Davies M.R. (1998) Fetal transplants placed into neonatal spinal transections in rats rescue axial muscle representations in adult motor cortex and improve recovery of l ocomotion. J Neurophysiol 80:3021-3030
Kargo WJ and Giszter SF, (2000), Rapid corrections of aimed movements by combination of force-field primitives. J Neurosci 20:409-426
Giszter SF, Grill W, Lemay M, Mushahwar V and Prochazka A (2000) Intraspinal microstimulation: techniques, perspectives and prospects for FES, pp101-138 in Neural prostheses forrestoration of Sensory and motor function ed. KA Moxon and JK Chapin CRC Press
Hart CB and Giszter SF (2004) Modular premotor drives and unit bursts as primitives for frog motor behaviors. J. Neuroscience 24(22):5269-82.
Murray M, Fischer I, Smeraski C, Tessler A, Giszter SF. (2004) Towards a definition of recovery of function. J Neurotrauma. 21(4):405-13.
Giszter SF, Hart CB. Udoekwere UI. Markin S, Barbe C. (2005) A Real-Time System for Small Animal Neurorobotics at Spinal or Cortical Levels. Neural Engineering. Conference Proceedings. 2nd International IEEE EMBS Conference March 16-19, 2005 Page(s):450 - 453
Udoekwere UI, Mbi LT, Ramakrishnan A, and Giszter SF. (2006) Robot applied elastic fields at the pelvis of the spinal transected rat: a tool for detailed assessment and rehabilitation. Proceedings of the IEEE/EMBC Conference, New York, NY.
Giszter SF. (2007) Spinal Motor Primitives. In The Encyclopedia of Neuroscience, (forthcoming).
John Houle, Ph.D. – Department of Neurobiology and Anatomy
Dr. Houle has a long standing interest in spinal cord injury and the potential to promote structural and functional repair in acute and chronic injury situations. It is important to understand that a spinal cord injury is an evolving condition where for weeks to months after injury there continues to be change/modulation of the cellular and molecular components affected directly or indirectly by the injury. These changes often are most prominent at the site of injury but it is critical that we also understand how cells/tissues remote to the injury are affected. An example would be the effect of spinal cord injury on neurons in the brain that normally transfer information through axon pathways that have been damaged. The response to injury by neurons in the brain may include cell atrophy, cell death, change in gene expression, retraction of the damaged axonal process or an attempt to re-grow the damaged axonal process.
Research in the laboratory is designed to examine multiple aspects of the neuronal
and glial cell response to spinal cord injury with the intent of designing a
combinatorial treatment strategy for regeneration leading to functional recovery.
To accomplish this difficult task we use a variety of approaches, including:
1) neurotransplantation to provide a substratum that will support the regrowth
of injured axons and which may provide a source of precursor cells to form new
neurons and glial cells, replacing those lost after spinal cord injury; 2) treatment
with neurotrophic and/or growth factors to provide essential molecules for cell
survival and for initiating and maintaining axonal growth; 3) modulation of
glial scar tissue and associated extracellular matrix to reduce the negative
features of what has been characterized as a structural and chemical barrier
to axonal growth; 4) exercise of injured limbs in the attempt to maintain joint
fluidity and muscle strength and to re-train regions of the spinal cord that
have been separated from descending input from the brain. There is strong evidence
of activity dependent plasticity within the brain and spinal cord after exercise
and we are especially interested in applying physical therapy and rehabilitation
medicine techniques to determine if enhanced spinal cord plasticity will translate
into greater behavioral recovery. As more information is gathered and placed
into the puzzle, our understanding of the sequence of steps to be followed to
promote recovery of function will become clearer.
Research techniques used in the laboratory range from gross anatomical examination to quantifying gene expression of single neurons. A typical experiment will include animal surgery, transplantation, physical therapy, a battery of behavioral analyses, preparation of tissue samples for light microscopy and immunocytochemical detection of specific cell types or tissue components, isolation of specific cells by laser micro dissection for extraction of RNA for analysis of gene expression by quantitative PCR, isolation of proteins for analysis of cell signaling by Western Blot or multiplex arrays.
Representative Publications
Houle JD, V Tom, D Mayes, G Wagoner, N Phillips, J Silver. 2006 Combining an autologous peripheral nerve bridge and matrix modification by chondroitinase allows robust functional regeneration across a hemisection lesion of the adult rat spinal cord. J. Neuroscience, 26: 7405-7415.
Beaumont E, JD Houle, CA Peterson, PF Gardiner. 2004 Fetal spinal cord transplant and passive exercise help to restore motoneuronal properties after spinal cord transection in rats. Muscle & Nerve 29:234-242.
Dolbeare D, JD Houle. 2003 Glial cell line-derived neurotrophic factor (GDNF) promotes neuroprotection and neurorepair after spinal cord injury. J. Neurotrauma 20: 1251-1261.
Peterson CA, RJL Murphy, EE Dupont-Versteegden, JD Houle. 2000 Cycling exercise and fetal spinal cord transplantation act synergistically on atrophied muscle following chronic spinal cord injury in rats. Neurorehab and Neural Repair 14: 85-91.
Dupont-Versteegden EE, RJL Murphy, JD Houle, CM Gurley, CA Peterson. 2000 Mechanisms contributing to restoration of muscle size with exercise and fetal transplants after spinal cord injury. Am. J. Physiol. 279: C1677-C1684.
Murphy RJL., EE Dupont-Versteegden, CA Peterson, JD Houle. 1999 Two experimental
strategies to restore muscle mass in adult rats following spinal cord injury.
Neurorehab. Neural Repair 13:125-134.
Michel Lemay, Ph.D. – Department of Neurobiology and Anatomy
My research interests are in movement control, and how neurophysiological findings may be applied to neuroprosthetics or orthotics design. Existing clinical neuroprostheses use electrical activation of the last-order neurons to individually command the muscles involved in producing movements. Thus, control of multi-joint motor behaviors remains one of the premier challenges for motor system neural prostheses. Since neurophysiology studies have shown the significant contribution of the spinal circuitry to movement control, the hypothesis is that electrical activation of spinal neural circuits, rather than direct activation of last-order motoneurons, will simplify generation of complex motor behaviors. Activation of these spinal circuits has been proposed as a possible new technique for the restoration of movement in spinalized individuals or the retraining/augmentation of regenerated pathways in the same population. My primary current project looks at the locomotor recovery provided by transplants producing nerve growth factors, combined with sensorimotor training of the locomotor circuitry, and the effects of these interventions on the motor output obtained by intraspinal microstimulation. In collaboration with colleagues, I am also looking at more physiological methods of activating the spinal circuitry. The project investigates the possibility of activating spinal neural elements via photolytic uncaging of the excitatory neurotransmitter glutamate.
Relevant Publications:
H Barbeau, DA McCrea, MJ O’Donovan, S Rossignol, WM Grill, and MA Lemay. Tapping into spinal circuits to restore motor function. Brain Research Reviews, Vol. 30, pp. 27-51, 1999.
SF Giszter, WM Grill, MA Lemay, V Mushahwar, and A Prochazka. Intraspinal microstimulation: techniques, perspectives and prospects for FES," in Neural Prostheses for Restoration of Sensory and Motor Function. KA Moxon and JK Chapin, Eds., CRC Press, 2000.
MA Lemay, JE Galagan, N Hogan, and E Bizzi. Modulation and vectorial summation of the spinalized frog's hindlimb end-point forces produced by intraspinal electrical stimulation of the cord. IEEE Transactions on Neural Systems and Rehabilitation Engineering, Vol. 9, pp. 12-23, 2001.
SF Giszter, JT Scabich, G Ellis-Davies, KJ Simansky, and MA Lemay. Photolytic uncaging of neurotransmitters as a control and stimulation device for neural tissues. Proceedings IEEE/EMBS, Austin, TX, 2002.
VS Boyce, M Bhowmik, MA Tumolo, I Fischer, M Murray and MA Lemay. Sensorimotor training and transplants of BDNF and NT-3 fibroblasts: their effect on locomotor recovery in spinalized cats. Proceedings of the 33rd Annual Meeting of the Society for Neuroscience, 2003.
MA Lemay and WM Grill. Modularity of motor output evoked by intraspinal microstimulation
in cats. J Neurophysiol, Vol. 91, pp. 502-514, 2004.
Gordon Lutz, Ph.D. – Department of Pharmacology
Duchenne Muscular Dystrophy (DMD) is caused by mutations in the gene encoding dystrophin, a membrane-associated cytoskeletal protein critical to muscle structural integrity. The mutations in dystrophin that cause DMD typically consist of false stop codons or insertions and deletions within the open reading frame (ORF) resulting in “out of frame” transcripts. Both types of mutations result in production of truncated protein that is targeted for cellular destruction. The loss of dystrophin in striated muscle weakens it structurally, making it more prone to cellular injury and degeneration. In DMD the normal processes of muscle regeneration cannot keep pace with the rate of muscle cell death, resulting in eventual replacement of muscle cells with fibrotic non-contractile tissue. DMD patients ultimately die in their late teens to early 20’s from cardiac and respiratory failure due to weakness of the respiratory muscles and myocardium, which is exacerbated by continued regression of the structural integrity of body musculature. There are no treatment options available for DMD.
Various approaches have been employed to express dystrophin in mdx mice, the classical murine model of DMD, which contains a false stop codon in the ORF, and is dystrophin-null. Because of concerns with viral safety, the development of non-viral approaches for induction of dystrophin expression has generated significant interest in the DMD community. It has consistently been demonstrated that 2’O-methyl and morpholino antisense oligonucleotides (AOs) can be used to cause "skipping" of various mutated dystrophin exons during pre-mRNA splicing, resulting in the production of partially to fully functional protein. Although AO-mediated exon skipping holds great promise as a therapeutic intervention for DMD, dystrophin expression levels in limb muscles have remained too low and functional improvements have been marginal with this approach. Moreover, no previous studies have achieved quantitatively significant levels of dystrophin expression following systemic delivery of AOs to diaphragm or heart, which are both greatly compromised in humans with the disease.
We recently demonstrated that amine-rich cationic PEG-PEI copolymers function as effective carriers for improved delivery of AOs to myonuclei, resulting in high transfection capacity and widespread appearance of dystrophin-positive fibers in mdx mice at 3 weeks after intramuscular injection.
Our current focus is to further improve the nanopolymer carriers to provide improved transport of the AOs from the bloodstream to target cells and facilitate cellular uptake. We propose that our improved carrier-AO compounds will provide high levels of dystrophin expression in body musculature and heart of mdx mice, resulting in a significant gain in muscle strength and reduced susceptibility to eccentric contraction-induced muscle injury.
Relevant Publications
Sirsi SR, Williams JH, and G.J Lutz. (2005) Poly(ethylene imine)-Polyethylene Glycol Copolymers Facilitate Efficient Delivery of Antisense Oligonucleotides to Nuclei of Mature Muscle Cells of mdx Mice. Hum. Gene Therapy. 16:1307-1317
Glodde M, Sirsi SR, and GJ Lutz. (2006) Physiochemical Properties of Low and High Molecular Weight PEG-Grafted Poly(ethylene imine) Copolymers and their Complexes with Oligonucleotides. Biomacromolecules. 7(1): 347-356.
Williams JH, Sirsi SR, and GJ Lutz. (2006) Induction of dystrophin expression by exon skipping in mdx mice following intramuscular injection of antisense oligonucleotides complexed with PEG-PEI copolymers. Molecular Therapy. 14(1):88-96.
Young-Jin Son, Ph.D. – Department of Neurobiology and Anatomy
Title: Synapse plasticity and repair in adult muscle and spinal cord
Our lab is interested in molecular and cellular basis of synapse plasticity in adult vertebrates. Neurons communicate each other through their specialized contacts called synapses, whose formation and maintenance are essential for proper functioning of the nervous system. Disturbance of such synapses in adults, therefore, by intrinsic or extrinsic factors such as pathological or physical damages, could be devastating. Notably, however, our nervous system has developed ways to cope with such occasions. Most prominently in the muscle, uninjured motoneurons sprout new axons and reestablish synaptic connections on injured muscle fibers, thus insuring muscle function and strength. In brain and spinal cord, limited but yet substantial plasticity of adult synapses has also been implicated in functional reorganization and restoration of adult brains. Our research goal is to elucidate biochemical mechanisms underlying such inherently extensive or limited plasticity of adult synapses. To this end, we currently focus on the role of perisynaptic glial cells (Schwann cells and astrocytes) as an active trigger of synapse plasticity both in muscle and spinal cord, a novel concept being developed in our laboratory. Various molecular and cellular techniques are being used, including state-of-the art tools and techniques such as in vivo imaging and transgenic mice. We hope that the work will lead to novel insights into synaptic roles of glial cells, pathogenesis of neurological and muscular diseases, and therapeutic strategy to repair synapses elsewhere in our nervous system.
Relevant publicationsMegan Wright, Wha-Ja Cho, and Young-Jin Son. 2007. Ciliary neurotrophic factor elicits intrasynaptically trapped sprouting of motor nerve terminals released by Botulinum toxin-elicited topological sprouting: Implications for neuromuscular synapse repair. J. Comp. Neurol., in press *cover article.
Anthony S. Burns, Sabiha Jawaid, Hui Zhong, Hiroyuki Yoshihara, Srishti Bhagat, Marion Murray, Roland R. Roy, Alan Tessler and Young-Jin Son. 2007. Paralysis elicited by spinal cord injury evokes selective disassembly of neuromuscular synapses with and without terminal sprouting in ankle flexors of the adult rat. J. Comp. Neurol. 500:116-33.
Flora M. Love, Young-Jin Son and Wesley J. Thompson. 2003. Activity alters muscle reinnervation and terminal sprouting by inhibiting the formation of Schwann cell pathways linking synaptic sites. J. Neurobiol. 54:566-576.
Young-Jin Son, Todd W. Scranton, William J. Sunderland, Sung J. Baek, Jeffery H. Miner, Joshua R. Sanes and Steven S. Carlson 2000. The synaptic vesicle protein SV2 is complexed with an ?5-containing laminin on the nerve terminal surface J. Biol. Chem 275(1) : 451-60
Young-Jin Son, Joshua T. Trachtenberg and Wesley J. Thompson 1996. Schwann
cells induce and guide sprouting and reinnervation of neuromuscular junctions.
Trends. Neurosci. 19(7): 280-285 *cover article.
Faculty Sponsors
Elizabeth Blankenhorn, Ph.D.
Department of Microbiology and Immunology
Drexel University
2900 Queen Lane
Philadelphia, PA 19129
215-991-8392
Elizabeth.blankenhorn@drexel.edu
Jeffrey S. Deitch, Ph.D.
Assistant Professor
Department of Neurology
MS 423
Room 7126 New College Building
245 North 15th Street
Philadelphia, PA 19107
215-762-7693
Jeffrey.deitch@drexel.edu
Simon Giszter, Ph.D.
Department of Neurobiology and Anatomy
Drexel University
2900 Queen Lane
Philadelphia, PA 19129
215-991-8412
(215) 843-9082 (fax)
simon.giszter@drexel.edu
Terry Heiman-Patterson, M.D.
Professor of Neurology
Director MDA/ALS Center of Hope
Department of NeurologyMS 423
Room 7102 New College Building
245 North 15th Street
Philadelphia, PA 19107
215-762-7692
(215) 762-3161 (fax)
terry.d.heiman-patterson@drexel.edu
John Houle, Ph.D.
Department of Neurobiology and Anatomy
Drexel University College of Medicine
2900 Queen Lane
Philadelphia, PA 19129
(215) 991-8295
(215) 843-9082
jhoule@drexelmed.edu
Michel Lemay, Ph.D.
Department of Neurobiology and Anatomy
Drexel University
2900 Queen Lane
Philadelphia, PA 19129
215-991-8412
(215) 843-9082 (fax)
mlemay@drexelmed.edu
Gordon Lutz, Ph.D.
Department of Pharmacology
New College Building
245 N. 15th Street, MS#488
Philadelphia, PA 19102
215-762-2396
glutz@drexel.edu
Young Jin Son, Ph.D.
Department of Neurobiology and Anatomy
Drexel University
2900 Queen Lane
Philadelphia, PA 19129
215-991-8274
(215) 843-9082 (fax)
yson@drexelmed.edu
DREXEL
UNIVERSITY COLLEGE OF MEDICINE
The
Edward Jekkal Muscular Dystrophy Association Fellowship
Application
Procedures
Purpose:
This program has been established to strengthen the training program for senior postdoctoral fellows about to move into faculty positions or junior research faculty members, including physician scientists, interested in neuromuscular disease research at Drexel University. The fellowship carries an annual stipend of $55,000 plus fringe benefits. The duration of the award will generally be 2 years.
Applicants are expected to identify a sponsor from within the training faculty
at Drexel University and to prepare an application with the sponsor, who will
provide the research support and, if appropriate, a salary supplement. Junior
faculty at Drexel University can submit an independent application. The research
project should be in an area consistent with the objectives of the Muscular
Dystrophy Association.
One original and 6 copies of the completed application (with 2 letters of recommendation)
should arrive at Drexel University by April 1, 2007.
No late submissions or
submissions sent by facsimile will be accepted.
Application forms are available in pdf format or msword format
Review Considerations:
Proposals will be judged by the Advisory Committee, with the aid of internal referees. The following criteria will be considered:
Review
Criteria:
- Scientific and research
background of the applicant
- Relevance of the proposed training to the career goals of the applicant
- Scientific quality of the proposal
- Appropriateness of the sponsor to the proposed training program and the sponsor’s
commitment.
Specific
Instructions for Applicant
Face Page
Self explanatory. If there
will be multiple sponsors, list the primary one here.
The earliest possible start date for the fellowship is July 1, 2007.
Education Information
Applicant’s Education - List all degree programs beginning with baccalaureate
or other initial professional education. Include all dates (month and year)
of degrees received or expected, in addition to other information requested.
Applicant’s Training/Employment - List in chronological order all nondegree
training, including postdoctoral research training, all employment after college,
and military service. Clinicians should include information on internship,
residency and specialty board certification (actual and anticipated with dates)
in addition to other information requested.
Goals for Fellowship Training and Career - Explain training goals under this fellowship and the relevance to your career goals. Identify the skills, theories, conceptual approaches, etc. that you hope to learn or enhance your understanding of during the fellowship. Describe how the proposed activities, including any research, will contribute to the achievement of these career goals.
Abstract - State the broad, long-term objectives and specific aims of the research proposal, making reference to the health relatedness of the project. Describe concisely the research design and methods for achieving these goals. Do not summarize past accomplishments and avoid the use of the first person. This is meant to serve as a succinct and accurate description of the proposed work when separated from the application.
Table of Contents
Self explanatory
Background
Support - Follow instructions on form.
Academic and Professional Honors - List any honors that would reflect upon your potential for a fellowship. Include current memberships in professional societies.
Title(s) of Thesis/Dissertation(s) - Self-explanatory.
Thesis Advisor or Chief of Service. If not submitting a reference from this person, explain why not.
Supplement - List any plans, if any, developed with the sponsor to supplement the stipend.
Research
Summary - Summarize in chronological order your research experience, including the problems studied and conclusions. Specify which problems were theses. If you have no research experience, list other scientific experience. Do not list academic courses here. Do not exceed one page.
Doctoral Dissertation - Summarize, not exceeding one page.
Publications - In chronological order, list your entire bibliography, separating abstracts, book chapters, reviews, and research papers. For each publication, give the authors in published sequence, full title, journal, volume number, page numbers, and year of publication. Indicate if you have used another name previously. Manuscripts pending publication or in preparation should be included and identified.
Research
Training Plan (Sections a-c not to exceed 5 pages)
Research Training Proposal - This section should be well formulated and presented in sufficient detail that it can be evaluated for both its research training potential and scientific merit. It is important that it be developed in collaboration with the sponsor. If multiple sponsors are envisioned, describe their individual roles.
a. Specific Aims - State the specific purposes of the research proposal and the hypothesis to be tested.
b. Background and Significance - Sketch briefly the background to the proposal. State concisely the importance of the research described in this application by relating the specific aims to broad, long-term objectives.
c. Research Design and Methods. Provide an outline of:
·Research design and the procedures to be used to accomplish the specific aims;
·Tentative sequence for the investigation
·Statistical procedures by which the data will be analyzed; and
·Any procedures, situations, or materials that may be hazardous to personnel and the precautions to be exercised.
Potential experimental difficulties should be discussed together with alternative approaches that could achieve the desired aims.
d. Literature Cited - Each citation must include names of all authors, titles, book or journal, volume number, page numbers, and year of publication.
Section II - Primary Sponsor
Facilities and Commitment
Follow instructions on form.
Checklist
The Checklist is the last page of the application.
Instructions for Submission of References
Applications will not be reviewed unless at least two references are received with the application. Applicants are responsible for complete applications reaching DUCOM on schedule.
Attach unopened references to the front of the original application and submit the entire package by the submission deadline.
Submitting Your Application
Submit the following materials in one package:
1. The original application, single sided, with signature. Note that the pages must be assembled in the order specified in the table of contents.
2. One original and 6 single-sided copies of the application. These should be made after signature.
3. At least 2 sealed letters of reference attached firmly to the Face Page of the original application.
Mailing Address
The Edward Jekkal Muscular Dystrophy Research Fellowship
c/o Dr. Itzhak Fischer
Department of Neurobiology and Anatomy
Drexel University College of Medicine
2900 Queen Lane
Philadelphia, PA 19129
Jekkal Fellowship Awardees
1996-1998 Kathrin L. Engisch, Ph.D.
2001-2002 Young Jin Son, Ph.D.
2005-2006 Wenqian Yu, Ph.D.
2005-2007 Anthony Burns, M.D.
2007-2009 Birgit Neuhuber, Ph.D.