Diffuse intrinsic pontine
glioma (DIPG) account for about 20% of pediatric brain tumors. Despite three decades of clinical research,
the survival rate of children with high grade gliomas (HGG; WHO Grades III and
IV) remains less than 10%.Diffuse
intrinsic pontine gliomas (DIPGs) are high grade brainstem gliomas (BSGs) that
remain uniformly fatal.Factors
contributing to the lack of progress include challenges in surgical resection
(inaccessibility to brainstem), poor availability of tissue, and lack of robust
animal models of the disease.
We have taken two steps in
order to overcome these obstacles and move rapidly towards molecular targeting
and preclinical study of DIPGs.
First, we have
formed a DIPG Consortium (DIPGC) that includes scientists from Johns Hopkins
University (JHU), National Cancer Institute (NCI) and Children's National Medical
Center (CNMC) in Washington DC.The aim
of this consortium is to establish a DIPG biobank, share existing DIPG
specimens and standardize DIPG specimen procurement and distribution amongst
has obtained murine models of DIPG: the genetically engineered model that over
expresses PDGF and two xenograft models that were recently generated at JHU and
CNMC sites by orthotopic injection of postmortem DIPG tumor cells. Integrated genomic and proteomic
characterizations of DIPG in humans and in murine models of DIPG are underway
at DIPGC sites.
Our team includes three experts in the field of pediatric DIPG. All three centers have extensive experience
in planning, overseeing, executing and analyzing experiments proposed in this
- The Children's
National Medical Center (CNMC) site is a world leader in expression profiling
and is also equipped with the cutting edge protein profiling technologies.
- The Johns
Hopkins University (JHU) site has an established track record of basic and
translational research on high-risk brain tumors. There is substantial
expertise in the establishment and propagation of neurosphere cultures and
tumor orthotopic xenograft models.
- The Pediatric
Neuro-Oncology Section of the National Cancer Institute (NCI) is considered a
worldwide referral resource for DIPG patients. Initial studies on DIPG tumor
tissue have been performed at the NCI in collaboration with Paul Meltzer, M.D.,
Ph.D., a renowned authority in gene expression analysis.
The purpose of this study is
to prospectively collect specimens from pediatric patients with diffuse
intrinsic pontine glioma or brainstem glioma, either during therapy or at
autopsy, in order to characterize the molecular abnormalities of this tumor.
Primary Outcome Measures:
- Genome-wide expression patterns of RNA in tumor samples, normal brainstem tissue and
cerebrospinal fluid using Affymetrix gene expression profiling
- Validation of results of the genome-wide
profiling of tumor, normal brainstem tissue and cerebrospinal fluid
expression patterns as assessed by immunohistochemistry and western blot
compared to normal brainstem tissue
analysis of tumor samples and normal brainstem tissue
- In vitro and in
vivo molecular analysis of collected samples
samples will be used for in vitro analysis and generation of animal models.
Javad Nazarian is an
investigator at the Center for Genetic Medicine in Children's National Medical
Center, Washington DC and as an assistant professor in Integrative Systems
Biology at the George Washington University.He received his PhD from the George Washington University in Genetic in
2005. His dissertation research involved
molecular profiling of neuromuscular junctions using laser capture
microdissection. His postdoctoral
research involved protein profiling of pediatric brainstem tumors.
Dr. Nazarian's laboratory
investigates establishing in vivo models of brainstem gliomas as well as
generating the molecular profile of the disease. These include proteomics, genomics, microRNA
and mRNA profiles. His multidisciplinary
team includes members from Neurosurgery, Neurology, Oncology and Research
departments. The team's ongoing research
involves characterizing in vivo and in vitro models of brainstem gliomas,
developing nanoparticles-mediated strategies for specific targeting of tumor
cells, and assessment of non-hormonal steroids for treatment of pediatric brain
External link to Dr.Nazarian's website at the George Washington University
||Eric H. Raabe, MD, PhD
Eric Raabe, M.D., Ph.D., is
an instructor in the Division of Pediatric Oncology and a physician-scientist
at Johns Hopkins.
majored in neural science at Brown University and received his M.D. and Ph.D.
from the University of Cincinnati College of Medicine. He completed his
pediatric internship and residency at Children's Hospital of Philadelphia.
After spending a year
working in Africa as part of the Baylor International Pediatric AIDS
Initiative, Raabe joined Johns Hopkins as a pediatric oncology fellow. Working
in the laboratory of Charles Eberhart in Neuropathology, Raabe established a
human neural stem cell system to create genetically accurate models of
pediatric brain tumors.
With an interest in
neuro-oncology, Raabe see patients in the pediatric oncology outpatient clinic
at Johns Hopkins.
He continues his research in
the new Smith Building of the Wilmer Eye Institute in the Neuropathology
Division, in collaboration with Charles Eberhart.
External link to Dr. Raabe's website at the Johns Hopkins School of Medicine
||Kathy Warren, MD
Dr. Warren received her B.S. in Medical Technology in
1982 and her M.D. from Tufts University School of Medicine in 1990. She
completed a residency in pediatrics at Children's National Medical Center,
followed by a fellowship in pediatric oncology at the National Cancer
Institute. She is board certified in pediatrics and pediatric
hematology/oncology. Dr. Warren is a Tenure Track Investigator in the Pediatric
Oncology Branch, specializing in neuro-oncology. Her research interests include
performance of clinical trials, particularly in children with tumors of the
central nervous system, non-invasive evaluation/imaging of the brain, and
neurotoxicity resulting from tumors and their treatment.
External Link to Dr. Warren
Website at the NCI