Javad Nazarian, Ph.D., Assistant Professor, Pediatrics, Children’s National Medical Center, Center for Genetic Medicine
The focus of my science career changed almost three years ago when a physician colleague approached me and proposed a potentially challenging project: molecular analysis of pediatric brainstem gliomas (BSGs). The project deemed challenging because of the lack of fresh frozen samples for laboratory studies. My colleague explained that in most BSG cases, neurosurgery is often ruled out when the tumor is diffused and biopsies are rarely taken to avoid any serious neuronal damage. Hence, three decades of clinical research has gone by resulting in little progress. What was so special about this project was that it was initiated and funded by the parents of a child with DIPG (diffused intrinsic pontine glioma). He understood the challenge and was willing to give it a try.
Although biopsies and fresh-frozen autopsies are rate, few formalin-fixed paraffin-embedded (FFPE) autopsy BSG samples are available. Formalin fixation, by crosslinking molecules, preserves cellular morphology, which is significant for histological and pathological screenings. To use these samples for molecular studies, tissue will have to go through a ‘de-waxing’ step, which releases some –but not all- of the DNA, RNA, and proteins. This indeed hinders biomarker discovery efforts.
In the past two years with the help and support of foundations such as Isabella Kerr Molina Foundation, Ladies Board of Visitors, and the Childhood Brain Tumor Foundation we have been able to develop methodologies to push forward and standardize the analysis of FFPE samples. Results of our efforts were published in the Proteomics-Clinical Application Journal in 2007.
Three years later my career focus has shifted and I foresee that for many years to come, my efforts will be dedicated to improving our understanding of pediatric BSGs. Through the help of parents of BGS patients and concerned physicians, we have now collected a few frozen autopsied samples. Our goal is to generate the complete molecular profiles of the tumor. This means that mRNA, miRNA, DNA and protein analysis of these samples will be generated so that we have a complete picture of the molecular events of the disease. I cannot emphasize enough, the importance of fresh frozen autopsied samples for research. Parents and foundations alike have helped us in many ways to improve our understanding of the disease. Together, I truly hope, we advance rapidly towards the development of targeted therapeutics for pediatric brainstem gliomas.
September 8, 2009
