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.
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.