Department of Neurological Surgery

E. Antonio Chiocca, MD, PhD, Chair

Completing its second full year in 2006, the Department of Neurological Surgery was again recognized in U.S.News & World Report’s listing of top-ranked clinical programs. Three neurosurgeons – Mario Ammirati, MD, MBA, Ehud Mendel, MD, FACS, and Atom Sarkar, MD, PhD – joined E. Antonio Chiocca, MD, PhD, Louis Caragine Jr., MD, PhD, John McGregor, MD, and Carole Miller, MD. Department faculty performed 1,439 neurosurgical procedures in 2006, including gamma knife radiosurgery, intensity-modulated fractionated stereotactic radiation therapy (IMRT) using a Peacock system, and angiographic procedures (compared to 836 in 2005). In addition, Mariano Viapiano, PhD, joined Yoshinaga Saeki, MD, PhD, Sean Lawler, PhD, and Balveen Kaur, PhD, as research faculty in the Dardinger Laboratory for Neuro-Oncology and Neurosciences, sharing an appointment in the Center for Molecular Neurobiology. Also in 2006, the Department participated in three clinical trials, received research funding exceeding $1.6 million and authored 38 publications, double the number from 2005.

Ongoing Research Programs

Dardinger Laboratory for Neuro-Oncology and Neurosciences – E. Antonio Chiocca, MD, PhD, codirects this laboratory along with Herbert Newton, MD, of the Department of Neurology, and oversees the research conducted within. Here are some highlights from 2006:

The laboratory of Yoshinaga Saeki, MD, PhD, develops therapeutic strategies for neurological, neoplastic and genetic disorders. One ongoing study involves the development and applications of herpes simplex virus (HSV)-based amplicon vectors, which are high-capacity plasmid-based vectors with full HSV infection machinery, for gene therapy and neuroscience research. A second research area involves the development and applications of engineered oncolytic HSV vectors for cancer therapy. A third project examines the roles of G protein-coupled receptors that upregulate cAMP signaling in the axonal outgrowth of neurons and neuronal differentiation of neural progenitor cells.
Balveen Kaur, PhD, and her lab team study changes that occur in the microenvironment of gliomas in response to treatment, hoping to learn how treatment strategies can be exploited to maximum potential. A major focus is investigating novel mechanisms to disrupt the changes in vascular biology that result from tumors to develop therapeutic strategies that may be used alone or in combination with oncolytic viruses (OV) to augment existing treatment modalities. Her team also studies the extracellular matrix of tumors to develop ways to enhance viral spread and infection to improve therapy. The Kaur lab is attempting to identify potential biomarkers in patient serum that will reflect the ongoing replication of OV in solid tumors.
Sean Lawler, PhD, and his lab team study cell signaling mechanisms in central nervous system disorders (cancer and neurodegeneration) to develop novel therapeutic approaches. Using a threedimensional cell culture system, they are investigating migration and invasion of glioma cells, mechanisms that present a major challenge in brain tumor therapy. They have identified a number of small-molecule drugs that block invasion and are testing these in animal glioma models. They also have identified genes that may be important in migration and invasion. In addition, Lawler’s team is examining the role of the microtubule- associated protein, tau, in neurodegeneration to explore a potential link between amyloid and tau, which may be critical in Alzheimer’s disease progression.
The lab team of Mariano Viapiano, PhD, studies the composition of the extracellular matrix (ECM) of gliomas. The ECM presents a major barrier to cell movement in the adult central nervous system, but invasive gliomas are impervious to inhibitory signals from the neural ECM and produce altered versions of matrix molecules that may help their invasive capacity. Viapiano’s team focuses on two families of matrix proteins: lecticans and link proteins. They are characterizing molecular events underlying the pro-invasive role of these proteins in gliomas. They also are developing reagents to disrupt the interactions of these proteins that promote glioma cell dispersion. By inactivating pro-invasive molecules in the glioma matrix, they can design strategies to limit disease spread and make these brain tumors therapeutically accessible.
Mario Ammirati, MD, MBA, and his microneurosurgical skull base laboratory develop surgical approaches to tumors at the base of the brain, educating residents in these techniques and partnering with private and non-private organizations to develop clinical technology. New surgical approaches that ask “What if?” in the operating room (e.g., “What if this tumor were approached from an angle rather than the conventional one?”) are explored in the laboratory on anatomical specimens under simulated operating room conditions and later translated to the clinical care of patients. Two ongoing projects are the quantification of exposure afforded by the endoscope and microscope in the endonasal-transphenoidal approach to the sella and suprasellar region, and investigating a navigational system and endoscope to remove the posterior wall of the internal auditory canal without disrupting the labyrinth via a retrosigmoid approach.
Ehud Mendel, MD, FACS, and his spine and spine cancer laboratory are evaluating physiologic forces that impact spinal health and methods to optimize the surgical therapy of spinal disorders. They are developing a patient-specific hybrid biomechanical model that uses a patient’s musclerecruitment pattern and spinal imaging to predict forces on spinal structures, and they are examining the relationship between spinal load and proinflammatory cytokine upregulation. In clinical studies, researchers are using kinematic measures of trunk motion and upright magnetic resonance imaging to evaluate biomechanical compromise under physiologic loading and thereby the extent of disorders of the lower back. Studies quantifying the relationship between physical and psychosocial occupational risk factors and low back disorders are also under way.
The nanomedicine laboratory team of Atom Sarkar, MD, PhD, is investigating the relationship between single-molecule mechanics and disease states, particularly the micromechanical mechanisms that underlie the formation of pathologic fiber in Parkinson’s disease and that regulate the migration and spread of glioblastoma multiforme tumors. Both projects rely on atomic force microscopy (AFM), which can identify single molecules, place them under mechanical stress, and establish their mechanical stability. Such measurements are important to determine clinically relevant correlations between cell stiffness/elasticity and “aggressive” behavior. Parkinson’s is a disorder of the motor system involving genetic and environmental factors. The root of the illness is the formation and aggregation of a-synuclein fiber, a multi factorial process. Understanding the single-molecule mechanics for the a-synuclein protein will shed light on the protein’s stability and preventing fiber formation, guiding the design of molecular therapeutics. As for neoplastic cells in glioblastomas, cell motility is unpredictable. The cellular cytoskeleton is a filamentous system of “ropes, cables, and poles” that provides rigidity to the cell and determines its mechanical properties and motility. Glial fibrillary acidic protein is an important and abundant element of the intermediate filament network, one of three cytoskeletal components in the malignant astrocytes of these tumors. AFM data from experiments with single molecules can be tailored into a macroscopic model for investigating the role of force in the invasiveness of glioblastoma multiforme.

Research Accomplishments of 2006

Department clinicians and researchers were active in professional organizations and received various institutional, regional and national awards for their expertise and accomplishments:

Louis Caragine, Jr., MD, PhD, received the residents’ annual Lawrence Mervis, MD, Teacher of the Year Award and was recognized in Who’s Who in Medicine & Health Care: Sixth Edition 2006-2007.
E. Antonio Chiocca, MD, PhD, served in the National Institutes of Health (NIH) Study Section for Developmental Therapeutics and on the National Cancer Institute (NCI) program project cluster review subcommittees C and D. He also was selected as one of the “Best Doctors in Ohio” by Columbus Monthly Magazine and elected to the American Society for Clinical Investigation, the Society of Neurological Surgeons, and as a fellow of the American Association for the Advancement of Science.
Clara Raquel Epstein, MD (second-year resident) was one of seven physicians nationally appointed to the Steering Committee of the American Medical Association’s (AMA) Minority Actions Consortium Hispanic Physician Outreach Initiative at the AMA’s annual meeting.
Jakob Godlewski, PhD (postdoctoral fellow), became the second recipient of the Jeffrey Thomas Hayden Foundation Endowed Fellowship, awarded as part of a $250,000 endowment to Ohio State over three years: The Jeffrey Thomas Hayden Foundation Endowed Fellowship Fund in Pediatric Brain Tumor at Ohio State’s James Cancer Hospital and Solove Research Institute.
Chris Karas, MD (third-year resident) was elected to the Alpha Omega Alpha Honor Medical Society (AOA). The only national honor medical society in the world, the AOA comprises members at any stage in their medical career, from students in medical schools through faculty.
Balveen Kaur, PhD, received the first grant award from the National Brain Tumor Foundation for a project titled “Anti-angiogenic treatment for enhancement of oncolytic virus efficacy.” Her article titled “Hypoxia and the hypoxia-inducible-factor pathway in glioma growth and angiogenesis,” published with her colleagues at Emory in April 2005, was recognized as the most frequently read article in the journal Neuro-oncology in May 2006.
Kazuhiko Kurozumi, MD, PhD (postdoctoral researcher), won first prize in the Therapeutic Section of a poster contest staged by Ohio State’s Comprehensive Cancer Center at its eighth annual Scientific Meeting for an entry titled “Anti-angiogenic treatment enhances antitumor effects of an oncolytic virus in an experimental rat glioma model.”
John McGregor, MD, served as president of the Ohio State Neurological Society from 2004-06 and as Ohio representative, northwest quadrant, on the Council of State Neurological Societies since 1999.
Ehud Mendel, MD, FACS, received a $150,000 spine fellowship donation from George Skestos and a $75,000 spine fellowship donation from SYNTHES Spine. He also was named clinical codirector of Ohio State’s Spinal Dynamics and Ergonomics Laboratory.
Carole Ann Miller, MD, received a 2006 Excellence in Teaching Award from Ohio State’s College of Medicine.
Yoshinaga Saeki, MD, PhD, served in the NIH National Institute of Neurological Disorders and Stroke (NINDS), Neurological Sciences and Disorders B (NSD-B) Study Section.
Atom Sarkar, MD, PhD, received a co-appointment as assistant professor in the Department of Chemical & Biomolecular Engineering.
Joshua Shroll, American Brain Tumor Association (ABTA) summer fellow in the laboratory of Balveen Kaur, PhD, won the ABTA’s Lucien J. Rubinstein Award for identifying a secreted protein that can be used as a potential biomarker for oncolytic viral therapy of brain tumors.