Research Opportunities for Neurology and Neurosurgery Residents and Fellows

The Department of Neurobiology and Anatomy consists of roughly 15 active research laboratories, all of which study various aspects of neuroscience relevant to human diseases, developmental disorders, and recovery after injury. Ongoing investigations in the department involve studies on whole animals as well as studies on various culture systems of neurons and glial cells. We are funded by several grants from the National Institutes of Health, including a “program project grant” to support our spinal cord research, as well as two training grants to assist in funding our postdoctoral fellows. The environment is vibrant, consisting of a great deal of interaction among the laboratories, several journal clubs, and a weekly seminar series. The department is well equipped with shared confocal microscopy as well as biochemistry facilities. There are also modern facilities for surgical procedures, and the individual laboratories are well equipped with several different kinds of microscopes and equipment for molecular biology. Neurology residents will be able to perform basic research that is highly relevant to the clinical setting. Opportunities include the following general areas of interest, but are constantly expanding as the department grows.

Diseases Related to the Neuronal Cytoskeleton
Disruption of cellular function underlies disease states. It is therefore of great importance to understand both the cell biology of healthy cells and how cellular processes are disrupted in diseased individuals. Several faculty members in our department have strong interests in the cell biology of neurons vis-a-vis their normal function and in response to injury. There is a strong focus on the use of modern biochemical, molecular biology and imaging methods. The laboratories of Drs. Peter Baas, Gianluca Gallo, and Douglas Baird focus on understanding microtubules and actin filaments, which are key components of the neuronal cytoskeleton. Dr. Baas has interests in understanding the roles of microtubule-related proteins (such as molecular motors and severing proteins) in the development of axons and dendrites, and in the regeneration of injured axons. Dr. Gallo’s laboratory is investigating the mechanism of axonal retraction. Axonal retraction is important to the establishment of correct connectivity patterns between neurons during development by removing inappropriate connections. However, axons also retract in the adult nervous system in response to injury. Retraction of axons following injury results in the loss of connectivity between neurons. Dr. Gallo’s laboratory is investigating the role of actin filaments and myosin motor proteins in driving axon retraction. The results of these studies are predicted to delineate potential molecular targets for therapies aimed at minimizing axonal retraction following injury. The laboratories of Dr. Baas and Dr. Gallo are also researching the cytoskeletal basis of axonal extension with the aim of determining methods to improve regeneration in the injured nervous system. Dr. Baird is interested in the behaviors of microtubules and actin filaments within the growth cones of axons that are extending during development and recovery after injury. In conjunction with Dr. Itzhak Fischer, a pioneer in the studies of tau (a microtubule-associated protein that goes awry during Alzheimer’s disease), Dr. Baas hopes to develop new strategies for studying the cell biological deficits that impair the brains of these patients. Drs. Baas, Gallo, and Baird actively collaborate and provide a vibrant environment for studying the cell biology of the neuronal cytoskeleton in healthy and injured neurons.

Spinal Cord Injury and Regeneration
For over twenty years, a group of faculty members in our department have joined together to study ways of promoting recovery after spinal injury. They have taken advantage of recent advances in stem cell biology, gene therapy, physiology of locomotion, bioengineering and pharmacological interventions to open new avenues for more effective treatment of this previously intractable condition. The spinal cord research center is engaged in an innovative and multidisciplinary program for studying the pathophysiology of spinal cord injury and the use of various therapeutic strategies that include transplantation, drug therapy, physical rehabilitation, functional electrical stimulation, biomaterials and robotics. The goal and mission are "to bridge the gap between the discovery phase and clinical application by optimizing promising research strategies and developing effective and responsible protocols to treat patients whose function has been limited by spinal cord injury." Most of the projects within the spinal cord research center already include clinicians at different levels and can therefore provide opportunities for Neurology residents that are interested in research. Dr. Marion Murray together with Dr. Alan Tessler use genetically modified cells, which secrete trophic factors to increases neuronal survival, encourage regeneration leading to recovery of motor function. The motor recovery is further enhanced by administration of agents that mimic transmitters, such as serotonin, that normally act as modulators of motor function. Dr. Itzhak Fischer is working on development of cellular and molecular strategies for cellular replacement and repair of spinal cord injury. His research projects are focused on the study and transplantation of neural stem cells and bone marrow stromal cells into the CNS. The work includes collaborations with clinicians at the Department of Neuroengineering, biomaterial engineers at the Drexel University and two biotechnology companies Neuronyx and Osiris Therapeutics. Drs. Simon Giszter and Michel Lemay are interested in the biomechanics of spinal cord recovery of function and utilizing spinal circuits responsible for movements in neural prosthesis applications. They use computer-based modeling of limb biomechanics, kinematic analysis of movement behavior, and in vivo stimulation and recording of force, motion and muscular activation in pre-clinical models.

Peripheral neuropathy
Our department also has strong interests in diseases that afflict the peripheral nervous system, both developmentally and later in life. Several research projects are currently underway and have particular relevance to peripheral pathopathies such as ALS and muscular dystrophies. Dr. Young-Jin Son studies how nerve-muscle synapses are properly formed and maintained during development and adulthood. Particular emphasis is given to novel muscular/glial components and their signal transduction pathways, which Dr. Son believes are essential for synaptic maintenance and potentially could be key to developing new strategies for clinical interventions to reverse degeneration of motoneurons or muscle fibers. Dr. Son is also interested in understanding how nerve-muscle synapses regenerate following nerve or muscle damages. This project focuses on the role of Schwann cells as an active trigger of the repair, a novel concept being developed in his laboratory. The goal is to understand how glial cells initiate and coordinate PNS repair, with the hope that the work will lead to novel insights into synaptic roles of glial cells, pathogenesis of neural and muscular disorders, and therapeutic strategy to repair synapses elsewhere in our nervous system. Dr. Baas is currently studying a novel class of new anti-cancer drugs which, unlike traditional cancer drugs such as the taxanes, do not appear to produce severe peripheral neuropathies in patients. However, this needs to be thoroughly evaluated in animal models. Dr. Gallo is studying the long axons produced by peripheral sensory neurons, with the aim of understanding how they regenerate after severing. Various molecular and cellular techniques are being used by these laboratories, which include contemporary tools and techniques such as tissue-specific inducible mouse transgenics.

Other opportunities
In addition to the major foci described above, the department has other areas of strength that are beginning to prosper. Drs. Baas and Baird are very interested in the issue of neuronal migration, which goes awry in developmental neurological diseases such as lissencephaly and autism. Dr. Timothy Cunningham studies potential mechanisms of neuroprotection that are highly relevant to the clinical setting. Dr. Manuel Castro-Alamancos is performing state-of-the-art neurophysiological analyses involving recordings from single cells in living animals. This work enables him, and colleagues including Drs. Barry Waterhouse and Michelle Page, to study issues relevant to epilepsy in animal models. Dr. Ramesh Raghupathi has recently joined our department, and leads a strong program covering all aspects of traumatic head injury. We are also eager for Neurology residents to bring their own interests to our laboratories, to even further expand our research into new areas of clinical relevance.