Neuro-Oncology Research

The Neuro-Oncology Program at the Children’s National Research Institute continues to have robust translational and basic research components. Javad Nazarian, Ph.D., MSc, leads the basic research activities and currently serves as Scientific Director of the Brain Tumor Institute. Laboratory efforts underway include:

• Those focusing on systemic detections of intracranial lesions (liquid biopsies)
• The biology and the molecular therapeutic targets of high-grade gliomas, including pontine gliomas and new therapeutics for Group 3 medulloblastomas with MYC amplifications

Basic science efforts have expanded nationally and internationally with the program’s inclusion in the Childhood Brain Tumor Tissue Consortium (CBTTC) of which Nazarian was recently named the Scientific Director; the CBTTC has recently received NCI funding. The translational program remains robust as Children’s National remains an active member of the Pediatric Brain Tumor Consortium (PBTC), the Pediatric (Pacific) Neuro-Oncology Consortium (PNOC), the Sunshine Network and the newly opened CONNECT Consortium. All these consortiums are focusing on novel means to treat childhood brain tumors with an emphasis on molecular-targeted therapy and immunologic approaches.

Over the past year, translational trials have been opened utilizing check-point inhibitors, vaccine studies for high-grade gliomas and diffuse intrinsic pontine gliomas (DIPG) are underway, and molecular-targeted trials for medulloblastomas, brainstem gliomas and low-grade gliomas are also being conducted. The low-grade glioma study utilizing a MEK inhibitor has progressed to the point that the MEK inhibitor study will soon be part of a Phase III study for newly diagnosed patients with low-grade gliomas. Roger Packer, M.D., director of the Brain Tumor Institute, has led multiple international consensus conferences on pediatric low-grade gliomas, which have resulted in new guidelines published for the evaluation and potential management of such tumors. He has also been named Scientific Director of the National Brain Tumor Society’s Defeat Pediatric Brain Tumor initiative.

Our Team

• Gene Hwang, M.D.
• Lindsay Kilburn, M.D.
• Javad Nazarian, Ph.D.
• Roger Packer, M.D.
• Yanxin Pei, Ph.D.
• Brian Rood, M.D.
• Yuan Zhu, Ph.D.

In 2014, CCIR established the Medulloblastoma Special Interest Group, which focuses on understanding the causative mechanism and improving the treatment of medulloblastoma. The group performs translational research to integrate advances in molecular biology with clinical trials, taking research from the “bench to the bedside.” Our researchers are testing Hif1a inhibitors, such as echinomycin, for the treatment of medulloblastoma.

The lab of Yanxin Pei, Ph.D., is interested in using mouse models to study the molecular and cellular mechanisms underlying the initiation, progression and therapeutic resistance of Group 3 medulloblastoma (MB). Currently, there are two major research focuses in the lab. The first focus is to identify the cell of origin for Group 3 MB. Data demonstrate that the MYC oncogene alone is sufficient to induce medulloblastoma, and Sox2+ cells in the developing cerebellum with MYC overexpression can develop tumors upon transplantation into the cerebella of immune-deficient mice. Characterization of these MYC-driven tumors reveals that they resemble human Group 3 MB at a histological, immunohistochemical and molecular level, indicating that Group 3 MB may originate from the Sox2 lineage during cerebellar development. The lab is investigating why Sox2+ cells in the cerebellum are uniquely vulnerable to MYC-induced tumorgenesis, whereas other cell types are resistant. These studies may contribute to the development of novel therapeutic strategies for blocking tumor progression and possibly preventing tumor relapse. 

The second focus of the lab is to investigate the function of tumor-derived glial cells in the progression, maintenance and recurrence of MYC-driven MB. Preliminary data demonstrate that MYC-driven MB cells create their own niche by giving rise to mature glial cells to maintain tumor growth. The investigators are interested in determining whether elimination of tumor-derived glial cells can induce tumor regression or increase the efficacy of standard chemotherapeutic drugs, thereby preventing tumor relapse.

Our Team

• Catherine Bollard, M.B.Ch.B, M.D.

• C. Russell Cruz, M.D., Ph.D.

• Melanie Grant, Ph.D.

• Gene Hwang, M.D.

• Roger Packer, M.D.

• Yanxin Pei, Ph.D.

• Brian Rood, M.D.

• Yuan Zhu, Ph.D.