Pediatric brain tumors are the most common solid tumors in children, with 5,000 new cases diagnosed per year in the United States. Around 17% of brain tumors in children age 0-14 years are pediatric high-grade gliomas (pHGGs). pHGG is the deadliest cancer in children, with the median survival time of only 12-15 months despite aggressive therapy. pHGGs show distinct features from their adult counterpart (adult high-grade gliomas), and no new therapy for the disease has been developed for over 3 decades. Therefore, the major problem we would like to tackle is to design mechanism-based therapies based on the onco-genomic features of pHGGs. Various high frequent mutations have been discovered in...

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Pediatric brain tumors are the most common solid tumors in children, with 5,000 new cases diagnosed per year in the United States. Around 17% of brain tumors in children age 0-14 years are pediatric high-grade gliomas (pHGGs). pHGG is the deadliest cancer in children, with the median survival time of only 12-15 months despite aggressive therapy. pHGGs show distinct features from their adult counterpart (adult high-grade gliomas), and no new therapy for the disease has been developed for over 3 decades. Therefore, the major problem we would like to tackle is to design mechanism-based therapies based on the onco-genomic features of pHGGs. Various high frequent mutations have been discovered in pHGGs, however, how these mutations lead to brain tumors and how we can specifically design new therapies based on these mutations are still unknown.

We recently discovered that some of these mutated genes are involved in regulating an important element in the cell called telomere. Telomere is a cap at the ends of DNAs in all of our cells to protect DNA integrity. When people age, telomeres will get shorter and shorter, and the length of the telomeres has been considered to be a key factor to determine the life spans in humans. That is why sometimes people call telomere "life clock". Cancers, unlike normal organs, have to find a way to make sure their telomeres do not get shorter so that they can divide indefinitely. Here, we will use multifaceted approaches to study telomere regulation in pHGGs, and we will also use various safe and effective drugs to specifically disrupt the telomeres of the cancer cells without affecting normal cells.

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