Inositol Polyphosphates Intersect with Signaling and Metabolic Networks via Two Distinct Mechanisms
Inositol-based signaling molecules are central eukaryotic messengers and include the highly phosphorylated, diffusible inositol polyphosphates (InsPs) and inositol pyrophosphates (PP-InsPs). Despite the essential cellular regulatory functions of InsPs…
Precision Medicine Approach for Children with Diffuse Intrinsic Pontine Glioma
OBJECTIVE: Children with diffuse intrinsic pontine glioma (DIPG) continue to have a dismal prognosis. Within the context of a multi-center trial, we evaluated whether genomic profiling, defined as…
Development of robust in vitro and in vivo preclinical models for diffuse intrinsic pontine glioma
Diffuse intrinsic pontine glioma (DIPG) is a tumor of the brainstem arising in the pons. Because of the critical anatomical location total surgical resection of the tumor is…
ACVR1-Mutant diffuse intrinsic pontine gliomas (DIPGS) acquire abeerant activin-mediated bmp pathway activation
Diffuse intrinsic pontine gliomas (DIPGs) are aggressive pediatric high-grade gliomas with no effective therapies. In 20-25% of DIPGs, seven gain-of-function mutations were identified in the Type 1 Bone…
A Novel Inositol Pyrophosphate Phosphatase in Saccharomyces cerevisiae: Siw14 Protein selectively cleaves the β- Phosphate from 5-Diphosphoinositol pentakisphosphate (5PP-IP5)
Inositol pyrophosphates are high energy signaling molecules involved in cellular processes such as energetic metabolism, telomere maintenance, stress responses, vesicle trafficking, and can mediate protein phosphorylation. While the…
Scalable Biobanking: A Modular Electronic Honest Broker and Biorepository for Integrated Clinical, Specimen and Genomic Research
Abstract: Biorepository research has introduced significant challenges to biomedical informatics systems design and implementation. We take a best-of-breed system integrative approach to finding solutions to administer a biobank operationally,…
Effects of TORC1/2 inhibitor MLN0128 alone and in combination with MEK inhibition in BRAF mutated glioma cells.
INTRODUCTION: First generation allosteric inhibitors of mTORC1 have shown clinical benefit for the treatment of pediatric low-grade gliomas (PLGG). MEK inhibition has shown great promise in early phase…
Targeted combinatorial approach for treatment of pediatric low grade gliomas in the context of BRAFV600E and KIAA1549:BRAF mutations.
Pediatric low-grade gliomas (PLGG) constitute the most common group of central nervous system tumors in children. Viewed as a chronic disease, ideal therapy for PLGG should carry limited…
Combinatorial pathway targeting approaches for BRAF fusions associated with pediatric low-grade gliomas.
INTRODUCTION: Activating BRAF-fusion mutations occur frequently in pediatric low-grade gliomas (PLGGs). We have previously shown targeting of KIAA1549-BRAF fusion by PLX4720, the research analog of vemurafenib, results in…
Exome sequencing identifies BRAF mutations in papillary craniopharyngiomas
Craniopharyngiomas are epithelial tumors that typically arise in the suprasellar region of the brain. Patients experience substantial clinical sequelae from both extension of the tumors and therapeutic interventions…