Panneerdoss Subbarayalu, PhD, to receive NIH, NCI R21 Grant, “Targeting the RNA Modifying Enzyme ALKBH5 in Medulloblastoma

Project Title: Targeting the RNA modifying enzyme ALKBH5 in Medulloblastoma

Principal Investigator: Panneerdoss Subbarayalu

Co-Investigators: Manjeet Rao, PhD, Andrew Brenner, MD, PhD., Peter Houghton, PhD.

Funding Agency: National Institutes of Health, NATIONAL CANCER INSTITUTE

Medulloblastoma is the most common malignant brain cancer in children. Despite the progress in treating medulloblastoma, the 5-year survival rate for high-risk medulloblastoma remains poor, and the risk of recurrence within two years of treatment is still high. The quality of life for those kids who do survive is substantially reduced due to the high toxicity associated with the radiation and chemotherapy they must endure at such an early age. These facts underscore the importance of identifying novel targets that can treat the disease effectively without any toxicity and offer long-term benefits. We discovered that ALKBH5, a protein that removes methylation marks from RNA, supports medulloblastoma growth. Interestingly, we discovered that ALKBH5 may support medulloblastoma growth by promoting the survival of medulloblastoma stem cells, which facilitate medulloblastoma to come back and also not respond to radiation. We believe that the successful completion of this study will provide a strong rationale to block ALKBH5 activity and consequently medulloblastoma growth with novel ALKBH5 inhibitors that we are currently characterizing. The current study will also validate ALKBH5 inhibition as a bonafide approach for sensitizing radiation response and therefore lowering the dose of radiation required for treating medulloblastoma patients.

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Since 2004, UT Health San Antonio, Greehey Children’s Cancer Research Institute’s (Greehey CCRI) mission has been to advance scientific knowledge relevant to childhood cancer, contribute to understanding its causes, and accelerate the translation of knowledge into novel therapies. Greehey CCRI strives to have a national and global impact on childhood cancer by discovering, developing, and disseminating new scientific knowledge. Our mission consists of three key areas — research, clinical, and education.

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