Unique Postdoctoral Training Program in the Neurosciences at Drexel University

Drexel University College of Medicine has been awarded a multi-year training grant for Postdoctoral Fellows in the Neurosciences. The training program affords postdoctoral fellows a very unique opportunity to be trained in multiple laboratories and to obtain a wide breadth of experiences, skills, and knowledge. The program is designed to fully equip postdoctoral fellows to compete successfully in the highly competitive world of biomedical research. The program is ideal for candidates who are seeking a richer, more interactive, and more career-based training experience than provided by a more typical postdoctoral fellowship. There are four focal groups in the program: cellular/developmental neurobiology, spinal cord injury and regeneration, neuroengineering, and systems/behavioral neuroscience. The training grant may only fund citizens or permanent residents of the USA. Unfortunately, we cannot consider applications from foreign scholars who are not permanent residents. Potential applicants are encouraged to contact individual faculty members with whom they share interests for more details and information. Formal applications must include a complete CV and three letters of recommendation sent by hard-copy through the post to: Dr. Peter W. Baas, Director of Neuroscience Postdoctoral Training Program, Drexel University College of Medicine, 2900 Queen Lane, Philadelphia, PA 19129.

1. Cellular and Developmental Neurobiology

Peter W. Baas, Professor (peter.w.baas@drexel.edu)
Dr. Baas is interested in the mechanisms that establish the microtubule arrays within the neuron during normal development of the nervous system and also during regeneration following injury. Microtubules are prominent cytoskeletal elements that are utilized in dividing cells for the formation of the mitotic spindle. Neurons are terminally postmitotic cells that no longer undergo cell division, but instead utilize their microtubules for the outgrowth of elongated processes termed axons and dendrites. Microtubules provide essential architectural support for these processes, and also act as railways for the transport of cytoplasmic organelles within them. In addition, differences in the organization of microtubules within axons and dendrites provide the basis for the morphological and compositional differences that distinguish these two distinct types of processes from one another. To study the mechanisms by which the microtubule arrays of the neuron are established, Dr. Baas uses a variety of cellular, molecular, and live-cell techniques. These techniques include various types of light and electron microscopy, genetic manipulation of individual cells, and the use of fluorescent probes to image the behaviors of microtubules within living neurons. Work from the Baas laboratory suggests that the mechanisms that establish the microtubule arrays of the neuron are modifications of the same mechanisms that organize microtubules within the mitotic spindle of dividing cells. Recent studies of the mitotic spindle indicate molecules termed microtubule-associated motor proteins generate forces that push and pull the microtubules into their appropriate pattern of organization. Dr. Baas’ studies indicate that the same is true with regard to the microtubules of axons and dendrites. Microtubules are manufactured within the cell body of the neuron, and then must engage specific motor proteins in order to be conveyed into axon and dendrites in the appropriate manner to establish the patterns of organization appropriate for each type of process. Dr. Baas is currently identifying microtubule-associated motor proteins within the neuron, and studying their specific roles in the differentiation of the axonal and dendritic microtubule arrays. Dr. Baas is also studying a family of proteins that sever long microtubules into shorter microtubules, thus making them more amenable to transport and reorganization. These studies will yield new information that can be used to develop novel strategies for augmenting the regenerative capacity of central and peripheral neurons.

Gianluca Gallo, Associate Professor (gianluca.gallo@drexel.edu)
Dr. Gallo investigates the cytoskeletal and signal transduction mechanisms involved in axon extension and retraction during development, regeneration and injury. He uses primary neuronal cultures to study cellular mechanisms in vitro. Biochemical and molecular biological methods are used to analyze the functions of cytoskeletal and signaling proteins in neurons. Microscopic techniques are used to monitor the behavior of living neurons and GFP-labeled cytoskeletal proteins using time-lapse methods. The methodologies most frequently used in the laboratory include western blots, protein purification, plasmid preparation and purification, transfection of primary neurons, confocal microscopy, multi-channel time lapse imaging of living neurons, immunocytochemistry, pharmacology, and peptide-based protein delivery into living cells. Current projects include: (1) studies on the mechanisms of injury-induced axon retraction, (2) roles of Rho-family GTPases in the responses of axons to guidance signals with relevance to regeneration (e.g., myelin and neurotrophins), (3) studies of the dynamics and regulation by signaling pathways of actin filaments in living neurons using time-lapse imaging of GFP-actin and other cytoskeletal proteins, (4) investigations on the role of actin filaments in regulating axon morphology and tension, and (5) the mechanisms of slow axonal transport. The Gallo laboratory also actively collaborates with engineers from Drexel University to develop new methodologies for the controlled patterning of cells on culturing substrata and the localized delivery of reagents to living cells in vitro.

Young-Jin Son, Assistant Professor (yjson@drexel.edu)
Dr. Son seeks to understand the molecular and cellular basis of the plasticity and repair of synaptic connections in the adult muscle and spinal cord. 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 denervated muscle fibers, thus insuring muscle function and strength. In spinal cord, limited but yet substantial plasticity of adult synapses has also been implicated in functional reorganization and restoration of adult spinal cords. The research goal of the Son laboratory is to clarify the features of adult plasticity of synaptic connections in muscle and spinal cord following injury, to elucidate the molecular and cellular mechanisms responsible for extensive or limited plasticity of adult synapses, and to use the knowledge to promote functional repair of damaged synaptic connections. Current projects include; 1) roles of muscarinic acetylcholine receptors, CNTF and cell adhesion molecules as synaptic triggers of motoneuron sprouting and glia reactivation. 2) identification of surface-bound, molecular trigger(s) reactivated synaptic glial cells use to induce sprouting of undamaged motor axon terminals. 3) analysis of instability and remodeling of muscle synapses following spinal cord injury and their contribution to compensatory recovery of motor function. 4) in vivo imaging analysis of the lack of intraspinal regeneration of DRG axons. Various molecular, cellular, electrophysiological and tissue culture techniques are being used, which include state-of-the art tools such as in-vivo time lapse confocal imaging, mouse transgenics and laser-capture microdissection. It is hoped that the work will lead to novel insights into synaptic roles of glial cells, pathogenesis of neural and muscular disorders, and therapeutic/rehabilitative strategy to promote repair of adult synaptic connections elsewhere in our nervous system.

Ramesh Raghupathi, Associate Professor (ramesh.raghupathi@drexel.edu)
Dr. Raghupathi's laboratory is focused on how cells respond to mechanical injury - not just what causes cells to die. In the mature brain, neurons and glia can respond to an injurious stimulus by either dying, becoming dysfunctional or by adapting to the altered extracellular milieu - i.e. plasticity. The goal of the research in this lab is to sort out the biochemical pathways that underlie the different responses to traumatic injury by utilizing well-characterized, clinically-relevant models of traumatic brain injury in the adult rat and mouse. Current studies focus on the role of mitogen-activated (MAPK) and stress-activated (SAPK) protein kinases, proteases such as calpains and caspases, in mediating cell death/dysfunction and axonal damage following trauma. The observation of SAPK/MAPK activation in injured axons and not just in neuronal cell bodies may be the basis for a unique mechanism by which axonal transport may be impaired and thereby serve as the biochemical basis for diffuse axonal injury. Although capsase-3 activation, the final step in the execution of apoptosis, has been documented following closed head injury, the mechanism(s) by which caspase-3 is activated in the different brain regions is(are) yet to be elucidated. The contribution of initiator caspases-8 and -9 in mediating caspase-3 activation is being evaluated in the laboratory using a combination of pharmacology (treatment of brain-injured rats with specific inhibitors to active caspases-8 and -9) and molecular genetics (using mice deficient in death receptors to inactivate caspase-8, and those deficient in Bax to inactivate caspase-9). A second, and equally important, focus of the research in the lab is elucidating the mechanisms underlying the response of the immature brain to traumatic injury. Clinical observations challenge the dogma that the immature brain is more resistant to mechanical injury - brain-injured infants and children under the age of 2 exhibit the worst outcome of all age groups. Dr. Raghupathi has developed a model of closed head injury in the neonatal (post-natal day 12) rat, an age that developmentally reflects the child less than 2 years and has reported that brain-injured rat pups exhibit long-lasting cognitive deficits and extensive brain atrophy. Current research, using a combination of biochemistry, electrophysiology and behavior, seeks to elucidate the cellular mechanisms underlying the susceptibility of the immature brain to trauma.

Yue-Qiao Huang, Assistant Professor
Dr. Huang’s lab is interested in the mechanisms that modulate the communication between neurons in the central nervous system. The general approach is to study the molecular mechanisms that regulate neurotransmitter receptors that mediate the response to neurotransmitters released at synapses. Currently the lab focuses the efforts on the regulation of the glutamate receptors, the major excitatory receptors in the brain. N-methyl-D-aspartate (NMDA) receptors, one of the most important glutamate receptor systems in the brain, play critical roles in learning and memory, development of the brain, and neurological disorders. Studies from this lab and from others have demonstrated that phosphorylation of glutamate receptors is a major mechanism for the control of their function and is critical for the regulation of synaptic communication. Moreover, Dr. Huang’s studies on the trafficking of the NMDA receptors have shown that receptor internalization may be a significant way of modulation of the synaptic plasticity. Current research projects include (1) cell signalling mechanisms for neurotransmission and plasticity, especially in long-term potentiation; (2) cell signalling in dendritic remodelling; and (3) trafficking of NMDA receptors. Dr. Huang’s research group uses a combination of state-of-the-art biochemical, cell biological, imaging, and electrophysiological approaches to address the questions of interest. As the glutamate receptors are critically important in brain disorders, Dr. Huang’s studies have significant implications that extend to a broad range of physiological and pathological processes in the central nervous system, including brain and spinal cord injury, epilepsy, chronic pain, stroke, Alzheimer disease, and other types of neurodegeneration. For example, it is now known that under-stimulation of certain receptors, such as glutamate receptors, may lead to decreased communication between neurons and may cause diseases such as Alzheimer's; in contrast over-stimulation of the glutamate receptors may cause neuronal death in stroke or CNS injury. Therefore, it is expected that augmenting the function and /or number of receptors in the brains of Alzheimer's patients, may enhance learning and memory; whereas decreasing the function or numbers of receptors could protect the neurons from death following a stroke or CNS injury.

Timothy Cunningham, Professor (timothy.j.cunningham@drexel.edu)
Dr. Cunningham is interested in the interaction of neurons and immune cells, especially following trauma to nervous system or in progressive neurodegenerative disorders. Like all tissue damage, one of the responses to neuron degeneration is inflammation. During inflammation, the secretions of immune cells (both circulating and intrinsic to the nervous system), can be particularly destructive to bystander cells and exaggerate injury. Immune mechanisms also contribute to the progression of chronic neurodegenerative disorders. This inflammation can occur through innate or acquired immunity so one line of research in the laboratory is to identify those aspects of the immune response that are particularly damaging to the CNS and which cell types are involved. At the same time the lab is interested in the defensive reactions of nerve cells because it is now clear that neurons have evolved evasion mechanisms that allow them to escape immune destruction. One such mechanism may involve the Diffusible Survival Evasion Peptide (DSEP), which was isolated from human neuroblastoma and later identified as a new endogenous human survival-promoting/immune evasion polypeptide. Peptide fragments of DSEP are biologically active and found to inhibit an inflammatory enzyme named secreted phospholipase A2 (sPLA2). A large effort is now devoted to defining sPLA2 involvement in models of traumatic brain injury and in degenerative disorders like Amyotrophic Lateral Sclerosis and Multiple Sclerosis. The Cunningham lab is also conducting ex vivo studies of humans with these diseases and developing new noninvasive procedures to monitor inflammation and correlated neuron/axonal destruction in humans and animal models.

Itzhak Fischer, Professor and Chair (itzhak.fischer@drexel.edu)
Dr. Fischer has two research programs, one on the structure and function of the neuronal cytoskeleton, and the other on transplantation strategies in spinal cord injury. Most of his efforts focus on the latter, but he maintains a strong interest in neuronal cytoskeleton, through collaborative interactions with the Baas group. With regard to this topic, Dr. Fischer studies the expression and function of cytoskeleton proteins, particularly microtubule proteins in the nervous system during development and regeneration in both the PNS and CNS. He uses biochemical, cellular and molecular approaches that include inhibition by antisense oligonucleotides, microinjection of recombinant antibodies, analysis of transcriptional regulation and trangenic animal models. He studies the role of MAP1B and tau in axonal growth, the mechanism of their phosphorylation and possible application of these genes to improve regeneration.

2. Systems and Behavioral Neurobiology

Barry Waterhouse, Professor (barry.d.waterhouse@drexel.edu)
Dr. Waterhouse seeks to understand the role of the central monoaminergic systems in brain function and behavior. More specifically he is concerned with the anatomy and physiology of the brainstem noradrenergic and serotonergic efferent systems as they relate to the sensory processing capabilities of the organism. These studies employ a broad spectrum of neuroanatomical and electrophysiological techniques including microiontophoresis, single unit extracellular recording from anesthetized animals, simultaneous spike train recordings from multiple arrays of single neurons in freely behaving animals, computer based acquisition and analysis of spike train data, mapping of afferent and efferent connections of monoamine nuclei using anterograde and retrograde tracers, and neurochemical identification of functionally characterized subsets of neurons in locus coeruleus and dorsal raphe nuclei. The underlying theme of this work is that synaptically released norepinephrine and serotonin operate as complimentary neuromodulatory substances that regulate the responsiveness of sensory neurons and sensory circuits to synaptic inputs according to changing behavioral contingencies. As such these systems may play a significant role in the ability of the organism to orient and attend to novel or salient stimuli from the sensory surround while at the same time suppressing responses to less salient stimuli. Clinical implications of this work which have led to related experimental studies are that these monoaminergic systems have a prominent role in stress-anxiety-depression, sleep disorders, ADHD, autism, and psychostimulant drug abuse and addiction.

Wen-Jun Gao, Assistant Professor
Dr. Gao’s major interest is the role of dopamine in prefrontal cortex function. This region of the brain is responsible for working memory, long term learning and emotional context of thought processes, and is implicated in the etiology of schizophrenia and other serious mental disorders. By studying the impact of this catecholamine on prefrontal cortical circuit operations at the level of neuron-neuron signaling interactions he hopes to better understand basic mechanisms of long-term learning and short-term working memory. Dr. Gao’s initial training was as a cortical neuroanatomist. He now employs combinations of neuroanatomy, electrophysiology, and pharmacology to address the actions of dopamine on pyramidal-interneuron, interneuron-pyramidal, and pyramidal-pyramidal cell recurrent excitatory interactions within the microcircuitry of the prefrontal cortex. In a state-of-the-art preparation Dr. Gao employs quadruple whole cell recording to study cell-cell communication within prefrontal cortical tissue slices. This powerful technique allows him to study dopamine modulation of transmitter release onto postsynaptic targets from single pyramidal neuron axon terminals. Dr. Gao’s long term goal is to translate his basic research on dopamine function to a clinically relevant analysis of schizophrenic neuropathology in animal models.

Manuel Castro-Alamancos, Professor (manuel.a.castro@drexel.edu)
Dr. Castro-Alamancos seeks to understand how the brain mediates behavior. The laboratory currently focuses on two research projects. One project investigates the dynamic properties of synaptic connections between and within the neocortex and thalamus, and how these function to acquire, analyze store and retrieve sensory information. The major aim of this project is to understand how synaptic networks function during information processing states, and thus to unravel what is the difference in the thalamocortical network between being awake and being attentive. This knowledge will have important implications for understanding several nervous system disorders that occur with deficits in information processing such as schizophrenia and learning disabilities. The second research project investigates the cellular and network mechanisms responsible for the generation of synchronized oscillations in the thalamocortical system during normal and abnormal (e.g. seizures) behavioral states. The major aim of this project is to understand how certain types of oscillations are generated within the intricate synaptic and cellular networks of the neocortex, and also what may be the functional role of oscillations that occur during normal behavioral states. This knowledge will have important implications for understanding several nervous system disorders that are associated with the occurrence of synchronous oscillatory activities such as epilepsy and sleep disorders. Work in the laboratory spans the fields of cellular, systems, behavioral and cognitive neuroscience. Dr. Castro-Alamancos studies the properties of synapses at the cellular level, neural circuits at the systems level and how synapses and circuits are modified through interactions with the environment at the behavioral level. Thus, the methodology used combines electrophysiological, pharmacological, neurochemical, morphological and behavioral techniques applied to acute slices of brain tissue maintained in vitro and whole animal preparations either anesthetized or freely behaving.

Shao-Pii Onn, Assistant Professor (shao-pii.onn@drexel.edu)
Dr. Onn is primarily interested in dopamine (DA) modulation of information processing in the prefrontal cortex (PFC) and how it affects subcortical structures like the nucleus accumbens in modeling psychiatric and neurological disorders involving a primary DA dysfunction. Ongoing research in her laboratory is to examine the neurophysiological basis for the development of hypofrontality in amphetamine- or nicotine-dependent rats. Using in vivo intracellular recording and labeling techniques in drug-dependent anesthetized rats, they characterize the intracortical-cortical connectivity (in the amphetamine model) and basal forebrain cortical transmission (in the nicotine model). Her previous work has shown that there exists enhanced synchronous activity between neurons in the prefrontal cortical output neurons via augmenting bistable membrane potentials and gap junctional conductances. This is particularly interesting as dendritic spine density and dendritic branching pattern of cortical pyramidal neurons reportedly increase in amphetamine-withdrawn animals. Increased density of dendritic spines may be linked to increased synaptic strength and thus may underlie the reinforced learning associated with drug-seeking behavior. Dr. Onn’s working hypothesis is that drug-dependent rats will have cortical deficits associated with abnormal oscillation and synchronization among distinct sets of pyramidal and non-pyramidal neurons of the limbic cortices. In a recent anatomical characterization of amphetamine-withdrawn rats, she employed confocal microscopy to identify alterations associated with a distinct GABA interneuronal cell type that is involved in the intralaminar inhibitory circuit. This selective alteration is further linked to enhanced synaptic activity in afferent axon terminals containing corticotrophin-releasing factor that is reportedly increased during withdrawal from drugs of abuse. She has also applied whole cell patch recordings assisted with differential infrared assisted videomicroscopy (DIC) in slices to preferentially target GABA interneurons to characterize the modulatory influence of nicotine exposure in different sets of GABA input. This is of particular interest as a deficit in cortical intrinsic GABA activity may underlie the cortical pathophysiology in drug dependency and schizophrenia. Collectively, using complementary in vivo and in vitro electrophysiological/anatomical approaches, Dr. Onn hopes to address the cortical pathophysiology in specific afferent input to the PFC, possibly contributing to what some clinicians have reported as hypofrontality in drug dependency that may underlie drug-seeking behaviors and associated emotional deficits.

3. Spinal Cord Injury and Regeneration

John D. Houle, Professor (john.d.houle@drexel.edu)
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. Research techniques used in the laboratory range from gross anatomical examination to quantifying gene expression of single neurons. A typical experiment includes 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.

Itzhak Fischer, Professor and Chair (itzhak.fischer@drexel.edu)
Dr. Fischer’s main focus is development of cellular and molecular strategies that promote nerve regeneration and recovery of function after spinal cord injury (SCI). His goal is to identify the best cells that are suitable for transplantation and to apply gene delivery methods to introduce therapeutic genes into the injured spinal cord. He is currently studying the properties and efficacy of genetically modified fibroblasts, neural stem cells, lineage-restricted precursors, and bone marrow stromal cells for grafting experiments. Using these methods he has demonstrated the complete rescue of injured neurons in Clarke's Nucleus by genetically modified cells that express NT-3 and the ability of cells that express BDNF to promote regeneration of rubrospinal axons and partial functional recovery. Grafting of fibroblasts that express both NT-3 and BDNF into a contusion injury improves not only motor function but also autonomic function of bladder control. He is also characterizing multipotent stem cells and restricted precursors isolated from embryonic spinal cord to establish their properties as intraspinal transplants with respect to survival, differentiation and therapeutic potential. He has shown that grafting neuronal-restricted precursors (NRPs) and glial-restricted precursors (GRPs) allow better survival and control over phenotypic fate than the multipotenial stem cells. This work has benefited from the availability of the alkaline-phosphate (AP)-transgenic rats as a source of labeled cells for transplantation. The lineage -restricted precursors (NRPs/GRPs) have been grafted into hemisection and contusion models of spinal cord injury. The analysis includes determination of phenotypic fate, host response (e.g., sprouting, regeneration) and recovery of function by a battery of motor, sensory and autonomic functions. The use of bone marrow stromal cells is clinically attractive because they can be easily be obtained from bone marrow, expanded and stored in “universal donor” cell banks, or used for autologous transplantation. A major effort is now directed in all the transplantation projects at combination therapy and development of non-invasive protocols that can be clinically applied.

Marion Murray, Professor (marion.murray@drexel.edu)
Dr. Murray is PI of the Program Project Grant on Mechanisms of Recovery after Spinal Cord Injury, PI of the subproject 3) Assessment and enhancement of transplant mediated recovery of function, and co-PI on subprojects 1) Genetically modified fibroblast grafts into spinal cord and 2) Application of neural stem cells in spinal cord injury. The primary research examines the evaluation of recovery of motor and sensory function that is mediated by cellular transplantation into spinal cord injury sites; the use of systemic administration of neurotransmitter and neuromodulator agents, particularly 5HT agonists, to further enhance sensory and motor function; and the contribution of intense motor training paradigms on recovery of motor function. Motor functions studied include locomotion, spontaneous limb usage, trained skilled movements, and bladder function. Both behavioral and kinematic measures are used to evaluate recovery. Sensory tests include evaluation of response to noxious and non-noxious stimuli. Some complex tasks, e.g. grid walking, are sensitive to both sensory and motor deficits. In collaboration with Drs. Tessler and Fischer, she is also comparing the efficacy of stem cells and genetically modified fibroblasts in restoration of function and the use of interventions in addition to transplants, e.g. blocking myelin inhibition, that should improve repair and therefore recovery of function.

Alan Tessler, Professor (atessler@drexel.edu)
Dr. Tessler’s main goal is to improve outcome in models of experimental spinal cord injury with the long-range goal of developing new strategies for treating spinal cord injury in humans. These studies require understanding the mechanisms responsible for neuron death after injury as well as the mechanisms that contribute to recovery. His primary treatment has been the use of fetal spinal cord transplants, and he has had to understand the mechanisms by which transplants assist recovery. He has also begun to use neural stem cells as transplants, which has required learning basic stem cell biology. Another approach involves forms of gene therapy, in which they administer neurotrophic factor and other types of genes to the damaged spinal cord by injecting adenovirus or genetically modified cells. This work involves close collaboration with the molecular biologists in the department. His collaboration with Dr. Murray has been longstanding and involves studies of locomotor recovery, behavioral pharmacology, and neuronal survival after axotomy.

Simon Giszter and Michel Lemay, Associate Professors
Dr. Giszters and Lemay are mainly affiliated with the Neuroengineering group, but their studies focus on issues directly relevant to the interests of the Spinal Cord group. This is evident from their research descriptions, provided in the next subsection.

Ramesh Raghupathi and Young-Jin Son, Associate and Assistant Professors
Drs. Raghupathi and Son are mainly affiliated with the Cellular and Developmental group, but they are also venturing into new areas of investigation relevant to spinal cord injury and repair, including molecular and cellular mechanisms underlying neuronal plasticity, cell death, sensory axon regeneration, and repair of intraspinal synaptic connections.

4. Neuroengineering

Simon Giszter, Associate Professor (simon.giszter@drexel.edu)
Dr. Giszter focuses on the organization of spinal cord subserving movement organization in isolation from descending pathways from the brain, and the way these mechanisms are integrated into normal voluntary movement. He is analyzing the biomechanics and neural controls organized by pattern generators and primitives that are involved in locomotion and reflex reaching movements such as the scratch or wiping reflex. The clinical value of this approach is that such mechanisms may form a part of the neural substrate for recovery of function following injury, may allow the development of new types of functional electrical stimulation (FES) and may assist in the design of new therapies for stroke, based on understanding of these elements. Whether or not primitives and pattern generators observed in other mammals and lower vertebrates are recruited as components of voluntary movement is a matter of controversy and an area of active investigation in which his and other laboratories are engaged. However, the relevance of these mechanisms to function and quality of life following CNS injury is not in doubt. Movement segments of fixed timing reminiscent of spinal primitives observed in other species have now been observed in stroke patients. Pattern generator and mass reflex elements are often components of spastic responses of paraplegics. Appropriate training, control and modulation of these elements may facilitate recovery of function and suppression of maladaptive responses. Their recruitment by FES may allow novel strategies to aid function. Further, efforts at Drexel and elsewhere aimed at extracting a cortical population vector representing movement intention may eventually be coupled to appropriate FES strategies such as these to allow a neural “bypass” of an injury site. Technologies able to exploit such approaches are rapidly becoming available. He is also examining the kinematics and biomechanics of the control of locomotion in rat by comparing normal rats to rats with transplant mediated recovery of function. This project is part of a larger effort involving several laboratories to discover new interventions to preserve and promote function following spinal cord injury. Trainees have opportunities to be involved in collection, analysis and synthesis of data from limb biomechanics (using robots, force platforms or sensors, and kinematic tools), electromyographic analysis, computational modeling and techniques of data analysis, electrophysiological recording of unit neural activity and intracellular recording and microstimulation applied to spinal cord or motor cortex.

Michel Lemay, Associate Professor (michel.lemay@drexel.edu)
Dr. Lemay is interested in neural prostheses and spinal circuitry. Neural prostheses are an emerging technology that use electrical stimulation of the nervous system to restore function to a damaged neuromuscular system. Current 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 guiding our approach is that electrical activation of spinal neural circuits, rather than direct activation of last-order motoneurons, will simplify generation of complex motor behaviors. His is one of only a handful of laboratories using this approach. These studies focus on the sub-movements elicited by stimulating interneuronal sites in the spinal cord, and the effects of plasticity and regeneration on the circuitry involved in producing these units of movements. Dr. Lemay’s research is thus of broad relevance to the fields of spinal cord injury research, neurophysiology, neuroengineering and neurorobotics.

Jonathan Nissanov, Associate Professor (jonathan.nissanov@drexel.edu)
Dr. Nissanov is pursuing a research program in imaging and computer vision methods for neuroinformatics and neurocartography. He is a particularly unique asset to the department and to the training program because he is focused on the development of ground-breaking new technologies for neuroimaging, one of the top priorities of the NIH in the neurosciences. He is working toward the goal of establishing a center for mouse neuroimaging at Drexel University that will be dedicated to the development of new microscope technologies and new software for image-analysis. Key technologies under development include image based query systems, spatial mouse brain normalization, new 3D optical imaging methods, and algorithms for segmentation of micrographs. The training environment in this laboratory is unique. The staff includes both engineers and neurobiologists. Postdoctoral training of engineers launches their career in the burgeoning field of neuroengineering, while neurobiologists are trained to develop new approaches to problems in neuroscience using techniques borrowed from engineering.

Other Neuroengineering Opportunities
Drexel University’s main campus provides a stimulating and innovative environment for engineering research and has made a major commitment toward the development of neuroscience-related engineering projects. For example, Dr. Karen Moxon works closely with Drs. Giszter and Lemay on their projects involving prosthetics and computational analyses of motor systems. In addition, there are neuroengineers collaborating with our cell/developmental neuroscientists, an example of whom is Dr. Bradley Layton, who is using nanotechnology-based micro-pinchers to measure and impose forces on axons growing in culture. Potential postdocs interested in any aspect of neuroscience related to engineering principles or applications will find our program to be rich with opportunities due to these interactions with Drexel’s superb main campus engineering departments.

Clinical Research Faculty
A defining feature of Drexel University is the strong focus on synergies and collaborations, and therefore, we have the strong support of all research faculty in clinical departments such as Psychiatry, Pediatrics, Surgery, Neurology, and Neurosurgery. These faculty are based at three different teaching hospitals, namely MCP Hospital, which is located near the Queen Lane building in the East Falls area of Philadelphia; Hahnemann Hosptial, which is located in the Center City area of Philadelphia, and St. Christopher’s Children’s Hospital, which is located in North Philadelphia. The clinical faculty members are uniformly eager and willing to collaborate and lend their expertise to the teaching and training of our postdoctoral fellows. In particular, the Chairs and the Dean have attempted to coordinate the hiring of clinical researchers with the basic research departments in order to ensure that mutual research interests are nurtured. For example, Dr. Carol Lippa, recently hired as the Head of Neurology at MCP Hospital, is widely recognized as one of the premier physicians in the Alzheimer’s field. She maintains a huge bank of Alzheimer’s tissue from her patients, is on the board of several journals and related foundations, and is invited to speak in forums around the world. Given that Alzheimer’s is a neurological disease with profound malfunctions of the axonal cytoskeleton, her interests beautifully complement those of Drs. Baas, Gallo, and Fischer on the microtubule systems of the neuron. Strength in Alzheimer’s research is augmented by Dr. Aleister Saunders, a biochemist and cell biologist located in Drexel’s Biology Department. In addition, the memory loss associated with Alzheimer’s is of great interest to the systems-level group led by Dr. Waterhouse. On a similar note, Dr. Richard Malone, a Professor of Psychiatry at MCP, is a world-expert in the area of autism, a neurological condition associated with sensory signal processing and the central monoaminergic systems and, thus, of great interest to Drs. Waterhouse, Onn, Page, and Castro-Alamancos. Recent work has shown that autism also involves abnormalities in neuronal migration, which is a topic of great interest to Drs. Baas and Gallo and the entire cellular and development group. The work of Dr. Susan McLeer, Chair of Psychiatry, on post traumatic stress disorder (PTSD) is also of interest to the systems-level group because of its relation to stress/anxiety and the monoaminergic systems. Dr. Christos Katsetos, a Research Associate Professor in the Pediatrics Department at St. Christopher’s Children’s Hospital, studies alterations in the cytoskeleton of brain tumors, and is working closely with Dr. Baas on this topic. The Spinal Cord group led by Dr. Murray has an extensive history of close collaborations with clinicians such as Dr. Alan Turtz, Associate Professor of Neurology at MCP, who is a recognized expert in surgical methods for reconstructing the spinal column after damage. Dr. Tessler, one of our primary trainers, is also an MD and a part-time clinician, and acts as the liaison between the spinal cord group and clinicians throughout the Drexel University system and the greater Philadelphia area. The Neuroengineering Group relies heavily on clinical interactions to guide their priorities in terms of the development of new prosthetic devices. Finally, our department has close ties with the ALS Foundation at Hahnemann Hospital, directed by Dr. Jeffrey Deitch. ALS involves impairment of axonal transport (studied by the cell and developmental group) which results in impairment in motion of the limbs (studied by the neuroengineering group).