The Research Foundation’s “Donor Wall,” on display since 1996, will again make an appearance at our next Annual Meeting in Philadelphia. Last year, ten corporations provided much needed support as part of our Corporate Associates Program (see accompanying box). This year, we hope for expanded support from our corporate friends, and a similar increase from you, our members. I encourage every one of you to reserve a place for your name on this display by making your commitment to the 1997 Campaign today!
Gifts to the Annual Campaign are placed in the Foundation Council’s designated endowment fund, which is currently valued at over $4 million. Income is then used to fund Young Clinician Investigator Awards and Research Fellowships. Since the first Awards were made in 1982, the Research Foundation has funded over $1.9 million to promising neuroscientists. Problems that have been addressed with Research Foundation funding include expanded study of brain tumors, neural regeneration, cerebral ischemia, epilepsy, movement and developmental disorders, and several other important areas. Earlier this year, the Scientific Advisory Committee provided for two Research Fellowships and two Young Clinician Investigator Awards, bringing to 46 the total number of projects funded in 15 years. All of us who have supported our Research Foundation should be proud of the advances that have been made as a result of this funding.
Despite these promising developments, there is still a long way to go. Each year, more than 35 grant requests are submitted to the Research Foundation. Unfortunately, because of a lack of funds the vast majority of these requests, all with vast potential, are left unfunded.
This year, we would like to substantially increase our member participation. With increased support from our members, there is potential for expansion of Research Foundation support to include more clinical studies. I believe that every member of the AANS should be happy to help this worthwhile endeavor. The routine techniques we use everyday all had their start in basic research.
A donation to the Research Foundation is a show of support for the future of our profession, an investment in tomorrow that will forever benefit the specialty.
Each donor will be listed in the Spring issue of the Bulletin, on our Web site NEUROSURGERY:// ON-CALL®, and will have their name on display on the Donor Wall. Group gifts of $1,000 or more will also be acknowledged in our Scientific Society. All neurosurgeons should consider joining the Cushing Scholars Circle; an minimum donation would be $1,000 for a Cum Laude level of giving.
As the end of the year approaches, everyone of us should be planning for our year-end giving. Even though most supporters give by check, there are many ways in which to give. You can make a pledge, and a pledge payment schedule can be established with periodic reminders. You can even make your gift using MasterCard or Visa. In these days of a rising stock market, you should consider making a gift of appreciated securities, deducting the full market value while likely avoiding all capital gains.
A gift can also be made as a tribute in honor of a colleague, friend or mentor, or as a memorial gift for a loved one who has passed away. Those you honor, or their surviving family members, will be notified of your unselfish generosity in their name.
Don’t forget that many of your patients, with a little encouragement, could be interested in supporting neuroscientific research. Our “Grateful Patient” brochures are still available, and can be very effective in soliciting funds to support research. This informative publication also gives an excellent presentation of the goals and mission of the Research Foundation. Contact Fund Development Officer John O’Connell at (847) 692-9500, or E-mail him at [email protected] for more copies of this useful brochure, or for any other help or information that you would like.
Research Foundation Announces 1997 Awardees
Applicants for the 1997 grants were of the highest caliber. I’d like to extend a public note of thanks to the members of the Scientific Advisory Committee for their efforts to identify the most outstanding applicants worthy of the financial support of the Research Foundation. A total of 33 applications were received, of which the following four individuals were selected. We are pleased with their selection and look forward to seeing the results of their efforts.
Lilyana Angelov, MD, BSc
1997 Research Fellow
University of Toronto
Chairman: Charles H. Tator, MD, PhD
Sponsor: Abhijit Guha, MD, MsC
Research Title: Ras Activity and Expression of Vascular Endothelial Growth Factor in NF-1 Peripheral Nerve Tumors
Abstract: Neurofibromatosis-1 (NF-1) is the most common familial cancer causing syndrome characterized by multiple peripheral nerve tumors. Neurofibromin, the protein encoded by the NF-1 gene is a negative regulator of activated Ras, and important intra-cellular signaling protein involved in cellular proliferation and/or differentiation. Loss of neurofibromin function results in elevated levels of activated Ras, contributing to unregulated proliferation in NF-1 related peripheral nerve tumors.
Angiogenesis, the formation of new blood vessels from pre-existing ones is vital for the growth of solid tumors. Angiogenesis results from a net balance of endogenous inducing factors, such as Vascular Endothelial Growth Factor (VEGF), opposed by endogenous angiogenic inhibitors. Activation of the Ras pathway transcriptionally upregulates VEGF, demonstrating a link between important mitogenic and angiogenic mediators. Whether this link between increased Ras activity, VEGF expression and angiogenesis exists in both benign and malignant NF-1 peripheral nerve tumors, will be explored. What we learn is not only applicable to tumors in NF-1 patients, but also the large number of human tumors where activation of the Ras pathway is implicated.
Amy B. Heimberger, MD
1997 Research Fellow
Duke University Medical Center
Chairman: Allen Friedman, MD
Sponsor: Darrell D. Bigner, MD, PhD
Research Title: Cytotoxic Lymphocyte Response Against Central Nervous System Tumors
Abstract: Our laboratory has identified a tumor specific antigen, EGFRvIII, on malignant gliomas and have shown that this antigen is able to induce an immune response that is cytotoxic specific and mediated by CD8+ cells in response to antigen presented within MHC I. With computer modeling based on crystallography, we have mutated peptides derived from the EGFRvIII antigen that can prime an immune response, initiate a cytotoxic response, and possibly circumvent the need for secondary signaling. We are currently demonstrating a murine model that in the presence of peptide tumor specific antigen a specific and effective cytotoxic response can be elicited and can suppress the progression of central nervous system tumors. The specificity of this response will minimize the induction of autoimmunity and will translate easily into clinical trials.
E. SANDER CONNOLLY, MD
1997 Young Clinician Investigator Columbia University
Chairman: Robert A. Solomon, MD
Sponsor: David J. Pinsky, MD
Research Title: Leukocyte Adhesion Receptors and Thrombosis in the Pathogenesis of Evolving Stroke
Abstract: Pilot data demonstrates that leukocyte adhesion molecules induce PMN capture, postischemic no-reflow, and tissue injury in experimental stroke. Preliminary studies of intracerebral fibrin formation and both PAI-1 and tPA mRNA expression also indicate that endogenous fibrinolytic mechanisms are inhibited. Because adhesion receptors can interact with platelets, and leukocytes may promote thrombosis, we hope to determine whether leukocyte recruitment and thrombosis synergize to exacerbate cerebral injury following stroke. Preliminary evidence for this synergy comes from P-selectin null mice which exhibit reduced cerebral thrombosis in stroke.
To expand these findings, we will determine the role of leukocytes and adhesion receptors in the pathogenesis of evolving stroke using adhesion receptor/counterligand deficient mice, and IL-1 receptor antagonist stragegy, along with an exploration of whether PMNs activate local proinflammatory signal transduction mechanisms (ie. NF-kB). We will also determine the role of thrombosis in evolving stroke, focusing on endogenous modulators of fibrinolysis (tPA, uPA, and PAI-1). Finally, studies focusing on synergism between thrombosis, fibrinolysis, and leukocyte recruitment will explore the role of MPs in cerebral fibrin formation and PAI-1 expression (using MP-deficient mice), test whether endogenous fibrinolytic mechanisms alter PMN capture, and test how PMN recruitment modulates thrombosis in stroke. We will also determine whether adhesion receptor blockade increase the efficacy and safety of thrombolytic therapy.
ADAM N. MAMELAK, MD
1997 Young Clinician Investigator California Institute of Technology
Chairman: William L. Caton, MD
Sponsors: Drs. Scott E. Fraser and
Erin M. Schuman
Research Title: Injury Induced Neuronal Reorganization in the Hippocampus
Abstract: Injury to the hippocampus can induce the sprouting of new axon collaterals from the dentate gyrus granule cell axons to their own dendrites, (“mossy fiber sprouting, MFS), forming a recurrent pathway for spontaneous hyperexcitability. MFS is therefore an attractive model for epileptogenesis. The goal of this project is to establish an in vitro hippocampal slice system for direct observation of MFS in real-time, using flourescence time-lapse microscopy. The pilocarpine seizure model will be used to induce MFS. Animals will be sacrificed at day 14-21 after pilocarpine administration, and hippocampal slices will be prepared. The granule cells will be flourescently labeled by either in vitro pressure injection of DiO into the slices, or in vivo stereotactic labeling with FGP-adenovirus. The flourescently labeled mossy fibers will be imaged on a two-photon laser scanning microscope for several hours, generating time-lapse movies of the sprouting process. This method will provide a powerful assay system for determining the effect of various biological modifiers on injury-induced axonal growth. As such, this research may significantly impact on our understanding of neuronal reorganization following seizure for other forms of injury.