Translational Research Accomplishments

The Neuro-Oncology Branch (NOB) laboratory has built an infrastructure to support clinical, basic, and translational research in neuro-oncology. In recent years, we have created a very large clinical practice from which to draw on for clinical and translational studies. We have also generated a vast genomic, molecular, cell line and glioma tissue database from which many research questions can now be answered. We have demonstrated our ability to maximize our resources resulting in new and important insights in glioma stem cell biology, glioma genomics, and glioma clinical/translational research. Brief examples of our accomplishments are detailed below:

  • Activated 11 clinical trials as a direct result of translational work performed within the Neuro-Oncology Laboratory

  • Identified 12 compounds through the preclinical screening program that have since been or are about to be brought forward to clinical trials at NIH (AZD6918, AZD8005, MLN-518, ZD6474, CC8490, LY317615, Sunitinib, Velcade/Tamoxifen, CC5013, Talampanel)

  • Generated and contributed the pivotal clinical trial companion data to Genentech’s FDA application that directly resulted in FDA approval of bevacizumab for recurrent GBMs

  • Demonstrated our ability to take a drug from the laboratory (enzastaurin), develop preclinical data supportive of clinical trials, conduct two Phase I and Phase II trials, and chaired a Phase III worldwide randomized registration clinical trial, while simultaneously discovering a novel mechanism of action of the drug (GSK3 inhibition) leading to new GSK3 inhibitors being brought into early phase clinical trials within NOB

  • Conceived, executed, and produced the Glioma Molecular Diagnostic Initiative (GMDI); one of the largest publicly open molecular, genomic, and clinical corollary, multiple platform databases in the world for any disease

  • In collaboration with the NCI Center for Bioinformatics, created REMBRANDT, a data warehouse and user-friendly bioinformatics toolbox for analyses of GMDI data for investigators of all expertise; GMDI and REMBRANDT were highlighted within the NCI Congressional Bypass budget and won the Congressional Service to America Award for Science and Technology in 2007

  • Provided some of the first published data in gliomas for four new potentially promising glioma molecular therapeutic targets (GSK3, notch, SCF, TrkA)

  • Contributed to the public scientific knowledge/database by making freely public (via GEO and/or caArray) expression arrays from 786 tumors and 123 glioma/tumor stem cell or normal neural stem cell lines and SNP data from 821 gliomas

  • Produced the first high-resolution SNP-based genomic survey of a large number (178) of gliomas of various histological types

  • Created a novel gene expression based glioma classification schema demonstrating two major groups of gliomas and six subgroups, each with distinct biological properties

  • Created bioinformatic tools at NIH whereby clinicians can instantly generate a SNP-based genomic survey of every patient’s glioma from FFPE sections and/or their gene expression profile-based tumor subgroup classification from fresh frozen tissue by merely pressing a button on their computer

  • Created coordinated clinical/laboratory SOPs such that GIC/GSCs (glioma stem cells) lines are generated for every glioma patient operated on at NIH

  • Was one of the first to provide evidence for the genomics and gene expression similarities between glioma initiating/glioma stem cells (GIC/GSC), and both their parental tumors and normal neural stem cells, and demonstrated how molecularly and genetically divergent standard utilized glioma cell lines are from primary gliomas

  • Provided one of the first examples of a temporally deregulated and aberrantly fixed normal stem cell developmental block to differentiation contributing to the pathogenesis of a human tumor by showing epigenetic deregulation of BMPR1b expression in GIC/GSC from a subgroup of GBM patients

  • Demonstrated that SSEA-1 (CD15) is a more ubiquitous marker than the commonly accepted CD133 marker for selecting for a population of cells enriched for GIC/GSCs properties