AANS/CNS SECTION
ON TUMORS

Hosts



Institution/Organization Name:  Brigham & Women’s Hospital 
Physician Sponsor:  E. Antonio Chiocca, MD, PhD 
Contact Information: 75 Francis Street, Department of Neurosurgery, PBB-301 Boston, MA 02115 
E-mail:Eachiocca@partners.org 
Phone: 617.732.6939

Research Category:

Anatomic studies
Angiogenesis
Cell/Tumor biology
Delivery Methods
Experimental therapeutics
Immunology
Invasion         
Outcome Studies
Pathology
Pediatric tumors
Preclinical models
Quality of Life
Radiation therapy
Radiology
Stem Cells
Tumor Genetics


 

Institution Name : UCLA Medical Center, David Gaffen School of Medicine. 
Physician : Antonio A.F. De Salles, M.D., Ph.D. 
Address: 200 UCLA Medical Plaza, Suite 504, Los Angeles, California 90095 
E-mailadesalles@mednet.ucla.edu 
Phone: 310-794-1221 

Research Interest/Projects:
The Stereotactic Section at the Division of Neurosurgery, UCLA we carry research in several areas of brain tumor treatment. Effects of radiation in the blood brain barrier, radisensitizers, radioprotectants, stereotactic radiosurgery technique improvement for brain and spine with frameless stereotactic approach. We have trials and oucome research on the treatment of various brain tumor histologies with Radiosurgery.


 

Institution : UCLA School of Medicine 
Physician : Linda M. Liau, MD, PhD 
Address: 10833 Le Conte Avenue, CHS 74-145, Los Angeles, CA 90095
E-mailLLiau@mednet.ucla.edu
Phone: 310-267-2621

Research Categories: Cell/Tumor Biology, Delivery Methods, Experimental therapeutics, Immunology, Preclinical model, Stem Cells, Tumor Genetic


 

Institution : Cedars Sinai Medical Center 
Physician : John Yu, MD 
Address: 8631 West Third St. #800E, Los Angeles, CA 90048
E-mailyuj@cshs.org 
Phone: 310-423-0845

Research Categories: Experimental therapeutics, Immunology, Preclinical models, Stem Cells

Research Interest/Projects
Neural Stem Cells to treat Cancer and Neurodegenerative Disease

Dr. John Yu's NIH funded laboratory at the Maxine Dunitz Neurosurgical Institute of Cedars-Sinai Medical Center is focused on novel cellular therapies for brain tumors and other neurological disorders using neural stem cells. Stem cells appear to be integral in the formation of brain tumors and research in the lab has demonstrated that neural stem cells may be used in the treatment of neurological disorders. The lab has made contributions in the field of cancer stem cells in the cause of brain tumors. Recent observations of the laboratory have demonstrated that these cancer stem cells are chemoresistant and may be the major reason for the recurrence of these deadly tumors. The lab has a major emphasis in the development of neural stem cells from bone marrow to treat brain tumors and neurodegenerative disorders. The goal is to dovetail this technology with ongoing dendritic cell vaccination trials to deliver a one-two punch. First, a systemic immune response will be generated in the periphery with dendritic cell vaccinations. Then, bone marrow derived neural stem cells expressing IL-23 will be delivered to the brain tumor to draw in memory T cells to the tumor.

Neural stem cells have the ability to track tumor cells and areas of neurodegeneration. This property will be exploited to use neural stem cells as delivery vehicles for tumoricidal or neuroprotective agents. The lab is collaborating to use a technology called Somatic Cell Nuclear Transfer to make embryonic stem cells using a normal oocyte with a transplanted nucleus from a donor who has ALS to study the cause of this disease. The goal is to make neurons from patients with ALS so that new therapies can be tested on these cells. The laboratory is actively developing a clinical protocol using neural stem cells derived from bone marrow to treat patients with brain tumors and neurodegenerative diseases such as Parkinson's disease and ALS. We are also collaborating with Dr. Michal Schwartz to develop clinical protocols involving vaccination and neural stem cell therapies for spinal cord injury, ALS, and stroke.

Neurosurgical fellows will have the opportunity to participate and write up clinical trials or basic research projects. They will be intimately involved in the development of their research project. Applications for further funding will be encouraged.


InstitutionCleveland Clinic/Brain Tumor Institute-Center for Translational Therapeutics

Physician: Michael Vogelbaum, MD, PhD, FACS
Address: 9500 Euclid Ave – R20, Cleveland, OH 44195
E-mail: vogelbm@neus.ccf.org 
Phone: 216-444-8564

Research Categories: Cell/tumor biology, delivery methods, experimental therapeutics, invasion, preclinical models

Research Interest/Projects:

We have a laboratory focused on aggressive preclinical testing of the most promising new anti-glioma agents. We have resources in place to evaluate the toxicity and efficacy of these compounds in the laboratory as well as in animal models of brain tumor. We also investigate the optimal route of delivery of these drugs in order to safely and, as quickly as possible, move them into clinical trials for the benefit of patients. We have collaborative research projects ongoing with a number of pharmaceutical and biotechnology companies, as well as with local, R01 funded investigators. What these projects have in common is that they involve novel drugs that are close to or in clinical trial and which are rationally designed to be effective against malignant gliomas given the molecular and genetic makeup of these tumors. These drugs are targeted against molecules such as EGFR, mTOR/Akt, Jak/STAT3 and Raf-1 kinase (projects have been in collaboration with Genentech, OSI Pharmaceuticals, Ariad, others). Our first translational clinical trial is with Tarceva/OSI-774, a selective EGFR kinase inhibitor small molecule drug. Other projects are focused on developing methods to improve immune response to gliomas (in collaboration with James Finke, Ph.D.), development of tumor specific modified siRNA molecules (in collaboration with Joao Marquez, Ph.D.) understanding the roles of STAT3 and NFkB in regulating glioma cell migration (R01 funding, in collaboration with Jahar Haque, Ph.D.), examination of the role of a newly identified phosphatase in regulating invasion of glioma cells (R01 funding, in collaboration with Susann Brady-Kalnay, Ph.D.) and exploring the use of a new drug which may sensitize gliomas to temozolomide (R21 funding, in collaboration with Stanton Gerson M.D.).


Institution: MD Anderson Cancer Center 
Physician: Oliver Bögler, PhD

Address: Unit BSRB 1004, 1515 Holcombe Blvd, Houston, TX 77030
E-mailobogler@mdanderson.org
Phone: 713-834-6216

Research Categories: Cell/Tumor biology, Experimental therapeutics, Preclinical models, Proteomics

Research Interest/Projects:

Signaling in the EGFR pathway - Insufficient signal attenuation plays a significant role in the overactivity of tyrosine kinases involved in the formation of gliomas. We are interested in a pair of adaptor proteins involved in receptor tyrosine kinase internalization, SETA/CIN85 and Alix. SETA is an SH3 domain adapter molecule whose expression is associated with the transformed state in astrocytes (3), and binds to Alix, itself implicated in atypical apoptosis (4). SETA binds to Cbl proteins, and promotes the internalization of active receptors. Interestingly, low levels of signaling, such as that of the oncogenic EGFR vIII, allows receptors to escape downregulation by Cbl-SETA (6). Alix negatively regulates the Cbl-SETA complex, protecting EGFR from downregulation (7). Src, in turn negatively regulates Alix/AIP1 by phosphorylation (5). We are pursuing this line of investigation to identify whether these mechanisms can be harnessed to downregulate oncogenic tyrosine kinase signaling in brain tumors.

Novel Platinum Compounds and Proteomics - We are interested in a new generation of polynuclear platinum compounds, which show greater efficacy and lower toxicity than cisplatin in glioma (1). Ongoing efforts focus on investigating the mechanism of drug action, developing strategies for combining them with other therapies to improve efficacy and develop them preclinically. In addition we are using proteomics (2) to generate profiles capable of predicting response. Planned acquisition of additional proteomics capabilities will allow us to expand these efforts to other areas of research, and collaborations with laboratories investigating cancer stem cells and biomarkers of response in glioma.

  1. Billecke, C., S. Finniss, L. Tahash, C. Miller, T. Mikkelsen, N. P. Farrell, and O. Bogler. 2006. Polynuclear platinum anticancer drugs are more potent than cisplatin and induce cell cycle arrest in glioma. Neuro-Oncol. 8:215-226.
  2. Billecke, C., I. Malik, A. Movsisyan, S. Sulghani, A. Sharif, T. Mikkelsen, N. P. Farrell, and O. Bogler. 2006. Analysis of Glioma Cell Platinum Response by Metacomparison of Two-dimensional Chromatographic Proteome Profiles. Mol Cell Proteomics 5:35-42.
  3. Bogler, O., F. B. Furnari, A. Kindler-Roehrborn, V. W. Sykes, R. Yung, H.-J. S. Huang, and W. K. Cavenee.2000. SETA: a novel SH3 domain-containing adapter molecule associated with malignancy in astrocytes. Neuro-Oncology 2:6-15.
  4. Chen, B., S. C. Borinstein, J. Gillis, V. W. Sykes, and O. Bogler. 2000. The glioma associated protein SETA interacts with AIP1/Alix and ALG-2 and modulates apoptosis in astrocytes. J.Biol.Chem. 275:19275-19281.
  5. Schmidt, M. H., I. Dikic, and O. Bogler. 2004. Src phosphorylation of Alix/AIP1 modulates its interaction with binding partners and antagonizes its activities. J. Biol. Chem.280:3414-25.
  6. Schmidt, M. H. H., F. B. Furnari, W. K. Cavenee, and O. Bogler. 2003. Epidermal growth factor receptor signaling intensity determines intracellular protein interactions, ubiquitination, and internalization. Proc.Natl.Acad.Sci.U.S.A100:6505.
  7. Schmidt, M. H. H., D. Hoeller, J. Yu, F. B. Furnari, W. K. Cavenee, I. Dikic, and O. Bogler. 2004. Alix/AIP1 antagonizes EGFR downregulation by the Cbl-SETA/CIN85 complex. Mol. Cell Biol. 24:8981-8993.

 

Institution/Organization Name:  Mass General Hospital 
Contact Information: 32 Fruit Street Yakey 9E – MGG Brain Tumor Center Boston, MA 02114 
E-mail:dcahill@partners.org 
Phone: 617-724-0884

Research Category:

Anatomic studies
Angiogenesis
Cell/Tumor biology
Delivery Methods
Experimental therapeutics
Immunology
Invasion         
Outcome Studies
Pathology
Pediatric tumors
Preclinical models
Quality of Life
Radiation therapy
Radiology
Stem Cells
Tumor Genetics 


 

       

Institution/Organization Name:  Mayo Clinic 
Physician Sponsor: Robert J. Spinner, MD 
Contact Information: Gonda 8-214 South, Rochester, MN 55905 
E-mail: spinner.robert@mayo.edu 
Phone: 507.284.2376

Research Category:

Anatomic studies
Angiogenesis
Cell/Tumor biology
Delivery Methods
Experimental therapeutics
Immunology
Invasion         
Outcome Studies
Pathology
Pediatric tumors
Preclinical models
Quality of Life
Radiation therapy
Radiology
Stem Cells
Tumor Genetics


 

Research Interest/Projects: mechanisms and imaging patters of benign and malignant peripheral nerve tumors with high resolution imaging (MRI, PET). Pathology of unusual peripheral nerve lesions. Outcomes of targeted fascicular biopsy. 



Institution
 : NYU School of Medicine 
Physician : Dimitris Placantonakis, MD, PhD 
Address: Department of Neurosurgery, NYU School of Medicine, 550 First Avenue, HCC Suite 3F, New York, NY 10016 
E-maildimitris.placantonakis@nyumc.org
Phone: 212-263-0092

Research Categories: Cell/Tumor biology, Experimental therapeutics, Invasion, Preclinical models, Stem Cells, Other: Skull base

Research Interest/Projects: Our laboratory studies glioblastoma stem cell biology with the goal of developing novel therapies for glioblastoma. Our studies utilize primary cultures of human glioblastoma stem cells from operative specimens that we obtain here at NYU. We are particularly interested in studying the molecular mechanisms underlying glioblastoma stem cell activation and migration under hypoxic conditions. To study this question, we are developing a novel xenograft model in mice that will allow us to track tumor stem cells in vivo using 2-photon microscopy. In addition, we are testing viral vectors with modified viral envelopes for their ability to specifically transduce glioblastoma stem cells within such tumors. Such selective vectors could facilitate the development of highly targeted molecular therapeutics in glioblastoma. In addition, our department has outstanding expertise in skull base surgery using both open and endoscopic approaches. We invite fellows with interest in skull base surgery to observe surgical approaches to the skull base performed at NYU and combine their clinical training with laboratory studies related to common skull base tumors, including meningioma, pituitary adenoma and chordoma.

 


Institution: Ohio State University

Physician: E. Antonio Chiocca, MD, PhD
Address:Department of Neurosurgery, Columbus, OH 43065
E-mailEA.Chiocca@osumc.edu 
Phone: 614-293-9312

Research Categories: Angiogenesis, Cell/tumor biology, delivery methods, experimental therapeutics, invasion, preclinical models, tumor genetics, gene/viral therapy


 

Institution : Penn State University 
Physician : Jonas M. Sheehan, MD 
Address: 500 University Drive – Department of Neurosurgery, Hershey, PA 17033
E-mailjsheehan@psu.edu 
Phone: 717-531-8807

Research Categories: Cell/Tumor biology, Delivery Methods, Experimental therapeutics, Invasion, Outcome Studies, Pediatric tumors, Preclinical models, Quality of Life, Radiation therapy, Tumor Genetics

Research Interest/Projects: Our current research efforts can be summarized as (i) development of nanovesicles and nanoparticles targeted to gliomas and delivery mechanisms for such particles, (ii) investigating the role of iron metabolism in brain tumors and the effects of particular genotypes of iron regulation/metabolism on the responses of cells to intervention (iii) prospective collection of tissue, intervention, outcomes and quality of life data for all patients with brain tumors in order to best determine predictors of quality of life and survival, and (iv) clinical impact of all interventions for brain tumors on quality of life and neurocognition.

Our basic and translational science efforts have progressed quickly. We have tested and validated our nanovesicle/nanoparticle approaches through animal models. We have a cell culture model of the blood-brain-barrier which allows us to examine the efficacy of transcytosis of nanovesicles and nanoparticles and modify them if necessary. In addition, we are continuing to explore alternative “payloads” to the targeted particles through our collaboration within the university and in industry. We are modifying the delivery system and schedule to maximize the additional benefits of siRNA use as well.

We have quantified abnormalities in iron metabolism and storage in tumor cells and are currently testing interventions to offset the treatment-protective effects of these abnormalities. Specific genotypes contributing to these irregularities are being evaluated from a prospective and retrospective clinical outcome standpoint.

Furthermore, our findings in the lab can be easily translated to research on patient outcomes through our standardized database which includes baseline clinical and neurocognitive variables before surgery, tissue and DNA collected during the operation, and then patients are followed prospectively over time for neurocognitive, functional, quality of life, and survival. For example, we are currently completing analysis of the effect of a genotype discovered in the lab on patients’ functional outcomes and length of survival. We are leaders in QOL and neurocognition research in brain tumors, and have a number of investigations of interventions focused on improving neurocognition and QOL as primary endpoints. Finally, we have an active industry-sponsored clinical trials portfolio in neuro-oncology and radiosurgery in addition to a busy clinical caseload of CNS tumors.


Institution: Stanford University Medical Center
Physician: Stephen L. Skirboll, MD
Address: Department of Neurosurgery,300 Pasteur Drive, R200, Standford, CA 94305
E-mailskirboll@stanford.edu 
Phone: 650-852-3450

Research Categories: Cell/tumor biology, stem cells, Cancer stem cells

Research Interest/Projects: My laboratory is seeking a visiting neurosurgeon to be part of our ongoing efforts to identify and characterize cancer stem cells (CSCs) in human malignant gliomas (MGs) and other brain tumors. We believe that CSCs are the only subpopulation of cells within a cancer that have the capacity to drive the formation and maintenance of a tumor. CSCs have been demonstrated in human leukemia and breast cancer by identifying cell surface markers that distinguish CSCs from cancer cells with more limited proliferative potential. Preliminary evidence has shown CSCs may also be present in MGs based on the expression of the cell surface marker CD133. However, our work and of others have not corroborated this, and we firmly believe the identity of CSCs in MGs is currently unknown. Because there are a relatively large number of cell surface markers that could possibly identify CSC in MGs, it is critical that a powerful screening approach be developed to accurately identify one or several candidate markers before proceeding with confirmatory testing using the time-consuming and costly in vivo mouse xenograft assays. Currently there is no such assay or approach that can screen hundreds of cell surface markers on living tumor cells to identify CSC subpopulations within MGs.

We have developed such an approach that combines an antibody-cell microarray with a soft agar assay which together can screen nearly 500 cell surface markers to identify those that enrich for growth of tumor colonies in vitro. We call this novel assay, the Colony-Forming Antibody Cell Array (CFACA), and the visiting neurosurgeon will use this to study both MG surgical specimens and cell lines. The cell surface markers which enrich for colony formation on the CFACA will then be used by the visiting neurosurgeon to prospectively sort (i.e. FACS) MGs for the desired subpopulations and test for: 1) enrichment in the colony forming efficiency using the traditional anchorage-independent soft agar assay, 2) enrichment in the formation of new tumors after intracerebral implantation into immunodeficient mice and 3) the demonstration of self-renewal and exact recapitulation of the original tumor with FACS of the malignant gliomas that form in the mouse and then serially implanting those sorted tumor cells to assess for tumor reformation. This will validate the CFACA as a powerful assay to screen for the identification of CSCs in MGs. The identification of CSCs in MGs will provide insights into glioma pathogenesis and establish a previously unidentified cellular target(s) for more effective MG diagnostics and therapies.

The visiting neurosurgeon will also have the opportunity to apply this novel approach to the study of non-neoplastic human brain tissue to attempt to identify candidate normal stem cells in human tissues. Moreover, there are a number of other modifications that can be done with this approach such as, first sorting the tumor for particular marker and than assessing the expression profile of that particular cell population, and profiling two separate populations on the same array using different fluorescent dyes. Furthermore, he or she will attempt to show differential expression of undifferentiated versus differentiated tumor cells which has relevance to better identifying unique markers of cancer stem cells in MGs and other brain tumors.


 

Institution Name: University of Alabama at Birmingham 

UAB is one of the 4 Brain Tumor SPORE sites and is engaged in and funded for basic science, translational and clinical research in a broad array of topics. We would be glad to serve as a SPONSOR for a Section on Tumors/BrainLAB International Research Fellow who would select to work under any of the following Investigators:

Physicians:

  • James M. Markert, M.D. - basic science, translational or clinical research in application of recombinant HSV to brain tumor therapy.
  • L. Burt Nabors, M.D. - basic science, translational or clinical research in glioma biology, glioma chemotherapeutics.
  • Candece L. Gladson, M.D. - basic science or translational research in anti-angiogenesis and anti-invasion targeting.
  • John Fiveash, M.D. - basic science, translational and clinical research with anti-death receptor antibody and radiotherapy.
  • Dale J. Benos, Ph.D. - basic science and translational research with anti-ion channel therapeutics
  • Etty N. Beneveniste, Ph.D. - basic science and translational research with NF-kB and STAT3 signaling therapeutics
  • Donald J. Buchsbaum, Ph.D. - basic science and translational research using adenovirus and herpes virus vectors encoding cytosine deaminase for molecular chemotherapy-radiotherapy
  • G. Yancey Gillespie, Ph.D. - basic science and translational research with anti-bioenergetics therapeutics.
  • Martin Johnson, Ph.D. - basic science and translational research on pharmacogenomics for malignant glioma therapy
  • Harald W. Sontheimer, Ph.D. - basic science and translational research on use of cystine-glutamate transporter and ion channel inhibitors

Please contact Dr. Gillespie or Dr. Markert for further information on the above listed physicians.

G. Yancey Gillespie, Ph.D.

Professor of Surgery, Microbiology and Cell Biology Director, Brain Tumor SPORE Division of Neurosurgery University of Alabama at Birmingham Room 1052 Tinsley Harrison Tower 1900 University Boulevard Birmingham, AL 35294-0006

voice: (205) 975-0438 fax: (205) 975-7667
cell: (205) 862-0557 UAB Pager: 5471 (205-934-3411)

James M. Markert, M.D., MPH
Professor and Chair, Co-Director - Brain Tumor SPORE, Division of Neurosurgery
1060 Faculty Office Tower, University of Alabama at Birmingham, 520 S. 20th Avenue
Birmingham, AL 35294-3410
voice: (205) 975-6985 fax: (205) 975-3203
email: jmarkert@uabmc.edu


 

Institution: University of Texas M.D. Anderson Cancer Center
Physician
: Seiji Kondo, MD, PhD 
Address: 1515 Holcombe Blvd. – Department of Neurosurgery - Unit BSRB 1004. Houston, TX 77030-4009
E-mailseikondo@mdanderson.org
Phone
: 713-834-6257

Research Categories: Cell/Tumor biology, Delivery Methods, Expermental therapeutics, Invasion, Preclinical models, Radiation therapy, Stem Cells


 

Institution/Organization Name : University of Toronto 
Toronto Western Hospital for Clinical-Translational ResearchArthur & Sonia Labatts 
Brain Tumor Center: Hospital for Sick Children's Research 
Inst. for Laboratory based research in molecular neurooncology 
Physician : Abhijit Guha 
Address
: 4W-446, Western Hosp, 399 Bathurst St Toronto, Ontario Canada M5T-2S8
E-mail
Abhijit.Guha@uhn.on.ca 
Phone
: 416-603-5740

Research Categories: Angiogenesis, Cell/Tumor biology, Experimental therapeutics, Invasion, Pathology, Preclinical models.

Research Interest:

  • Clinical-Translational Research: To be undertaken at the Toronto Western Hospital as part of our current neurooncology fellowship program, with involvement in surgically based neurooncology trials. The fellow would be part of a team comprised of several of my neurosurgical colleagues, clinical nurses, medical and radiation neurooncologists. The fellow would be expected to learn about designing and conduction clinical trials, running a tumor bank, pathological-molecular correlation studies, with some exposure to use of pre-clinical models.
  • Molecular Neurooncology Research: To be undertaken at Dr. Guha’s lab at the brain tumor center at Hospital for Sick Children’s Research Inst. The fellow would be part of my 11 person lab and also interact with other members of the tumor center, comprised of five other faculty members and their staff.
  • Overall theme of Guha lab: Molecular Regulators of Malignant Gliomas and Peripheral Nerve Tumors: Aberrant Signal Transduction Pathways; Angiogenesis and Microenvironment; Transgenic Mouse Models

Research Projects:

  • EGFR and mutant EGFR signalling pathways in astrocytomas: Proteomic based project to study the interactions, internalization, turnover and alterations in the proteome due to mutant EGF Receptors prevalent in malignant gliomas.
  • Transgenic modelling of human astrocytomas: Transgenic mouse glioma models to study relevant genetic interactions, glioma development, angiogenesis, drug response and discover novel glioma genes.
  • Angiogenesis and Glioma Microenvironment: Using human physiological MR guided samples from center and periphery of gliomas, isolating tumor and endothelial cells, to determine the influence of the microenvironment on the molecular and hence the pathological profile of GBMs

  • Peripheral Nerve Tumor Projects: Human peripheral nerve tumor samples are used to decipher their varying biological behavior at a molecular level. Second, xenograft models of malignant peripheral nerve tumors are used to determine efficacy of biological therapies, such as those against the Ras signaling pathway. Last, to use proteomic based approaches to determine what are additional neurofibromin interacting proteins, hence additional functions of relevance which when lost contribute to the large number of clinical manifestations found in NF1.

 


 

Institution/Organization Name:  University of Cincinnati Brain Tumor Center 
Physician Sponsor: Ronald E. Warnick, MD / Atsuo T. Sasaki, PhD 
Contact Information: 
Ronald Warnick, M.D. 
Chairman and President, Mayfield Clinic 
Director, UC Brain Tumor Center 
234 Goodman Street 
Cincinnati, OH45219 
Phone 513-221-1100 
E-Mail: nsgymd@mac.com

Atsuo T. Sasaki, Ph.D. 
Assistant Professor 
UC Cancer Institute,  
UC Brain Tumor Center 
3125 Eden Ave. Vontz Rm 2112 
Cincinnati, OH45267-0508 
Phone 513-558-2160 
E-Mail: atsuo.sasaki@uc.edu

Research Category:

Anatomic studies
Angiogenesis
Cell/Tumor biology
Delivery Methods
Experimental therapeutics
Immunology
Invasion         
Outcome Studies
Pathology
Pediatric tumors
Preclinical models
Quality of Life
Radiation therapy
Radiology
Stem Cells
Tumor Genetics

Research Interest/Projects: The University of Cincinnati (UC) has launched a new Brain Tumor Molecular Therapeutics Program aimed at understanding the biological mechanisms of cancer’s spread to the brain and developing more effective ways to treat the condition. The Molecular Therapeutics Program is believed to be the first translational, metastasis-specific program of its kind in the United States. 

This unique program consists a multidisciplinary team from UC College of Medicine and the Departments of Neurosurgery, Radiation Oncology, and Hematology-Oncology.  We have built a subspecialized research team that will collaborate with the existing brain tumor clinicians and surgeons to address the problem of brain metastases through translational research and original clinical trials. 

Brain metastases are secondary tumor sites that occur when cancer spreads from the point of origin to another organ or part of the body. Circulating tumor cells can be detected in the blood of cancer patients; however, not all these patients will develop brain metastases. A better understanding of how and why cancers metastasize to the brain would allow researchers to develop specific therapies to treat existing brain metastases and possibly prevent their formation. 

To address these problems, we focus on cellular metabolism to understand how metastatic cancer cells adapt to the microenvironment of brain. We particularly focus on nucleotide metabolism and its importance to supply energy to normal and tumor cells. We use innovative multi-system approach combining mouse genetics, immunohistochemistry, biochemistry, molecular biology, proteomics and metabolomics analyses.


Institution/Organization Name : Mount Sinai School of Medicine
Physician : Isabelle M. Germano, MD, FACS
Address
: Department of Neurosurgery – Box 1136, Mount Sinai Medical Center, One Levy Placy, New York, NY 10029
E-mailisabelle.germano@mountsinai.org 
Phone
:212-241-9638

Research Categories: : cell/Tumor biology, Delivery Methods, Experimental therapeutics, Outcome Studies, Pathology, Preclinical models, Quality of Life, Radiation therapy, Radiology, Stem Cells

Research Interests/Projects:

The Gene and Brain Tumor Laboratory of the Neurosurgery Department at Mount Sinai School of Medicine focuses on translational research for malignant gliomas. We focus on aggressive preclinical testing of the most promising new anti-glioma agents alone and in combination with radiation. The toxicity and efficacy of these compounds is evaluated in vitro on glioma cell lines and in animal models of brain tumor. We have published on laboratory and clinical trials using gene therapy and are still investigating some of the aspects of this modality. A more recent focus of the laboratory isembryonic stem cells (ESC). These totipotent cells with unlimited proliferative capacity, and, unlike other cell types, can be permanently and precisely genetically modified without the use of viral vectors.Clinical interests include use of image-guidance and non-invasive pre-operative brain-mapping for malignant glioma surgery

Selected publications:

Germano IM, Uzzaman M, Benveniste R, Zaurova M, Keller G.Apoptosis in human glioma cells produced using embryonic stem cell-derived astrocytes expressing tumor necrosis factor-related apoptosis-inducing ligand (TRAIL). J Neurosurgery 105:88-95, 2006

Uzzaman M, Benveniste R, Keller G,Germano IM. Embryonic stem cell-derived astrocytes: novel gene therapy vector for brain tumors. Neurosurgical Focus 19(3) E6, 2005

Benveniste R, Keller G, Germano IM. Embryonic stem cell-derived astrocytes expressing drug-inducible transgenes: Differentiation and allotransplantation into the mouse brain. J Neurosurgery 103:115-123,2005

Benveniste R. and Germano IM. Correlation of factors predicting intraoperative brain shift with successful resection of malignant brain tumors using image-guided techniques. Surg Neurol 63:542-549, 2005

Kanzawa T, Zhang L, Xiao L, Germano IM, Kondo Y, Kondo S. Arsenic trioxide induces autophagic cell death in malignant glioma cells by up-regulation of mitochondrial cell death protein BNIP3. Oncogene 24: 980-91, 2005.

Kanzawa T, Germano IM, Komata T, ito H, Kondo Y, Kondo S. Role of autophagy in temozolomide-induced cytotoxicity for malignant glioma cells. Cell Death Differ 11(4) 448-457, 2004

Kanzawa T, Bedwell J, Kondo Y, Kondo S, Germano IM. Inhibition of DNA repair sensitizes resistant glioma cells to temozolomide. J Neurosurgery 99:1047-1052, 2003

Germano IM, Fable J, Gultekin H, Silvers A. Adenovirus/herpes simplex-thymidine kinase/ganciclovir complex: preliminary results of a phase I trial in patients with recurrent malignant gliomas. J Neuro-Oncology 65:279-289, 2003

Kanzawa T, Komata T, Kyo S, Germano IM, Kondo Y, Kondo S. Down-regulation of telomerase acitivity in malignant glioma cells by p27k1p1. J Oncol 23:1703-8, 2003

Kanzawa T, Germano IM, Kondo Y,Ito H, Kyo S, Kondo S. Inhibition of telomerase activity in malignant glioma cell lines correlates with their sensitivity to TMZ. Br J Cancer 189:922-929, 2003

Yao K, Komata T, Kondo Y, Kanzawa T, Kondo S, Germano IM.Molecular response of human glioblastoma cells to ionizing radiations: cell cycle arrest, CDKI modulation, and autophagy.J Neurosurgery 98:378-384, 2003

Komata T, Kanzawa T, Takeuchi H, Germano IM, Schreiber M, Kondo Y, Kondo S. Antitumor effect of cyclin-dependent kinase inhibitors (p16INK4A, p18INK4C, p19INK4D, p21WAFI/CIPI and p27KIPI) on malignant glioma cells. British Journal of Cancer 88:1277-80, 2003.

Benveniste R and Germano IM. Evaluation of factors predicting accurate resection of high-grade gliomas using frameless image-guided stereotactic guidance. Neurosurgical Focus 14:1-4, 2003

Kanzawa T, Kondo Y, Ito I, Kondo S, Germano IM. Induction of autophagic cell death in malignant glioma cells by arsenic trioxide. Cancer Research 63:2103-2108, 2003

 


 

Institution/Organization Name: Virginia Commonwealth University, Department of Neurosurgery, Inova Campus in conjunction with George Mason University, Center for Applied Proteomics 
Physician: Joseph Watson MD 
Address
: Department of Neurosciences Office, Inova Fairfax Hospital 3300 Gallows Rd. Falls Church, VA 22042 
E-mail
joseph.watson@inova.org 
Phone
: 703- 776-8310

Research Categories: Cell/Tumor biology, Other: tumor proteomics

Research Interests/Projects:

Advances in CNS tumor biology, tumor genetics, and biochemistry have failed to uncover a final common pathway for histologically related tumors or for neoplasia in general. As a way to elucidate tumorogenesis and search for patient-specific treatments, we have been examining the protein profile of CNS tumors. This field of study represents a novel departure from genetic analysis, but is constrained by the limited availability of fresh, un-fixed human tissue. Brain and pituitary tumors removed at our large, community hospital (Inova Fairfax Hospital) are sent to pathology in an amount far in excess of that which is needed to make a histological diagnosis. We have an IRB- approved protocol in place to use this excess tissue as substrate for studying tumorogenesis by focusing on the protein profile, or proteome, of these neoplastic tissues. The proposed research is a translational study directly from the operating room to the laboratory, with the search for biological pathways that may be targets of therapy. Tumor specimens will be flash frozen in the operating room and a simultaneous serum specimen will be collected. These specimens will be grouped according to final histological diagnosis and examined in the laboratories at the Center for Applied Proteomics and Molecular Medicine, George Mason University. Specific cell populations will be targeted by Laser Capture Microdissection (LCM) and subjected to reverse phase proteomic analysis, with an emphasis on the network of phosphorylated proteins. Identification of tumor-specific protein networks in individuals and across histological groups will be possible. Further, we will develop reliable clinical testing algorithms for these protein pathways. This body of work is fundamental for creating individualized, tumor-specific biological treatment. Given the technical limitation of gene therapy, great promise lies in the elucidation of tumor pathways that may be interrupted by targeting protein or protein modification networks. Preliminary pilot data in glioblastoma has revealed significant clustering in tumors for certain protein pathways that correlate with clinical outcome. Further study in this area promises to uncover serum markers for disease. Ultimately, the search will include a final common pathway of tumorogenesis with respect to the protein mediators of cell function and survival. Visiting investigators will participate in tumor collection, processing with microdissection and analysis with protein microarrays and mass spectroscopy. They will be involved in the planning of experiments and the analysis of data and preparation of papers for talks and publications. Patient interaction will be encouraged, based on experience.

 


 

Institution/Organization Name: University of California, Irvine
Physician: Yi-Hong Zhou
Address
: MedSci C214, ZOT 1700-80, Irvine, CA, 92697
E-mail: yihongz@uci.edu 
Phone
: 949-824-5767

Research Categories :Angiogenesis, Cell/Tumor biology, Invasion, Outcome Studies, Stem Cells, Tumor Genetics, Other: Molecular-based model for glioma prognosis

Research Interests/Projects:

We are the first discovered tumor suppressive function of PAX6 in malignant glioma cell lines and favorable prognostic value of PAX6 for patients with WHO grade IV glioblatoma multiforme (median survival 0.9 to 1 year). We also revealed PAX6’s unfavorable prognostic value for patients with WHO grade II and III gliomas (median survival 4 to 7 years). We have been seeking an answer to PAX6’s conflicting role in different glioma types. Our current research data suggest a content-dependent function of PAX6 in glioma development and the role of PAX6 in brain tumor neural stem-like cells and GBM heterogeneity maintenance. Our recently published paper revealed tumor suppressive and therapeutic effect of an extracellular matrix protein EFEMP1, which is encoded by a target gene of PAX6. We are studying EFEMP1 in inhibiting EGFR/PTK2/AKT signaling pathways and developing tumor-suppressive extracellular signaling peptide out of EFEMP1 as a novel therapeutic agent to still the malignant behavior of cancer, thus to achieve therapeutic improvement of survival for patients with advance cancers. We have been studying glioma prognosis for a decade, focusing on developing multivariate models to improve outcome prediction, identify potential new therapeutic targets and uncover potential biomarkers for disease severity and/or progression in glioma patients.

 


 

 

Institution Name : Department of Neurosurgery, Weill Cornell Medical College 
Physician : Antonio Bernardo, MD
Address: 510 East 70th Street, Baker F2212
E-mailanb2029@med.cornell.edu 
Phone: 212.746.1468

Research Categories:

Anatomic studies
Angiogenesis
Cell/Tumor biology
Delivery Methods
Experimental therapeutics
Immunology
Invasion         
Outcome Studies
Pathology
Pediatric tumors
Preclinical models
Quality of Life
Radiation therapy
Radiology
Stem Cells
Tumor Genetics
Other: Skull base surgery, vascular neurosurgery

Research Interest/Projects:
The training technique with this program is geared towards the surgeons who have special interest in Skull Base and Vascular Neurosurgery. Lesions of the skull base present a unique challenge to neurosurgeons. Special training is required to perform intricate surgery in the small recesses of the brain. Most skull base neurosurgical approaches demand that surgeons be proficient not only with the tools but also with complex anatomy to be negotiated. The training site is the Microneurosurgery Skull Base Laboratory at Weill Cornell Medical Center. The laboratory is a state of the art facility which integrates exquisite cadaveric dissections, 2-D visualizations, virtual reality and computerized simulation for training of surgical procedures and visuospatial skills. In the laboratory complex approaches to the cranial base are performed on cadavers under conditions that simulate an actual operation as closely as possible. The program includes the following objectives:

  1. Define cadaver prosection models to investigate new surgical routes to access intracranial targets
  2. To gain experience in teaching neurosurgeons and residents the visuospacial skills required to navigate through various skill base neurosurgical approaches
  3. To achieve adequate preoperative training and rehearsal of complex approaches to the cranial base.
  4. To provide an opportunity to publish and establish expertise in a subspecialty area.

The program focuses attention on the training of neurosurgeons in the care of patients with pathology in the skull base region. The fellowship will include independent cadaveric dissection to promote practice and rehearsal of complex approaches to the skull base. The fellow will work closely with Dr. Bernardo for th purpose of education and for development of new neurosurgical techniques. Upon completion of the training program, the surgeon should have an improved understanding of cranial base anatomy and skull base surgical techniques.