Neoplasia. 2022 Dec 11;35:100861. doi: 10.1016/j.neo.2022.100861. Online ahead of print.
NO ABSTRACT
PMID:36516489 DOI:10.1016/j.neo.2022.100861
- Cooney T, Lindsay H, Leary S, Wechsler-Reya R.
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Dr. Robert Wechsler-Reya talks about his work with RCIGM.
In 2016, the Institute established the Joseph Clayes III Research Center for Neuro-Oncology and Genomics. This was made possible by a generous $10 million endowment from the Joseph Clayes III Charitable Trust. Under the direction of Robert Wechsler-Reya, The Center aims to accelerate the translation of leading-edge genomic research into prevention, diagnosis, treatment and cures.
“The first instinct of parents who have a child diagnosed with cancer is to seek out the best treatments available,” said Stephen Kingsmore, MD, DSc, President and CEO of Rady Children’s Institute for Genomic Medicine.“That’s exactly what our team of scientists, researchers and physicians aim to provide. By sequencing the tumor, we can discover the genomic foundation of the cancer, and develop individualized approaches to treatment.”
The Joseph Clayes III Research Center for Neuro-Oncology and Genomics brings together childhood brain cancer researchers to accelerate the translation of new findings and knowledge into prevention, diagnosis, treatment and cures.
The endowment is divided into three specific programs:
Neoplasia. 2022 Dec 11;35:100861. doi: 10.1016/j.neo.2022.100861. Online ahead of print.
NO ABSTRACT
PMID:36516489 DOI:10.1016/j.neo.2022.100861
Nat Commun. 2022 Dec 6;13(1):7506. doi: 10.1038/s41467-022-35118-3.
NO ABSTRACT
PMID:36473869 DOI:10.1038/s41467-022-35118-3
Cancer Res. 2022 Oct 20:CAN-22-0945. doi: 10.1158/0008-5472.CAN-22-0945. Online ahead of print.
ABSTRACT
Deregulation of N-myc is a leading cause of malignant brain tumors in children. To target N-myc-driven medulloblastoma, most research has focused on identifying genomic alterations or on the analysis of the medulloblastoma transcriptome. Here, we have broadly characterized the translatome of medulloblastoma and shown that N-myc unexpectedly drives selective translation of transcripts that promote protein homeostasis. Cancer cells are constantly exposed to proteotoxic stress associated with alterations in protein production or folding. It remains poorly understood how cancers cope with proteotoxic stress to promote their growth. Here, our data unexpectedly revealed that N-myc regulates the expression of specific components (~5%) of the protein folding machinery at the translational level through the major cap binding protein, eukaryotic initiation factor eIF4E. Reducing eIF4E levels in mouse models of medulloblastoma blocked tumorigenesis. Importantly, targeting Hsp70, a protein folding chaperone translationally regulated by N-myc, suppressed tumor growth in mouse and human medulloblastoma xenograft models. These findings reveal a previously hidden molecular program that promotes medulloblastoma formation and identify new therapies that may have impact in the clinic.
PMID:36264168 DOI:10.1158/0008-5472.CAN-22-0945
Robert Wechsler-Reya, PhD is also a professor and researcher at the Sanford Burnham Prebys Medical Discovery Institute (SBP) where he is focused on investigating the genes and nervous system signaling pathways that contribute to medulloblastoma, the most common malignant brain tumor in children.
© 2023 Rady Children's Institute for Genomic Medicine.
