Projects Funded (All Years)
2020 Projects Funded
RNASeq “in the round”
Nick Foreman
Creation of a single-cell atlas of pediatric brain tumors (year 2 of 2)
Nick Foreman
Pre-Clinical modeling of drug efficacy in pediatric brain tumors
Rajeev Vibhakar
High-throughput drug screening in pediatric brain tumors for rapid clinical translation
Nicholas Foreman
Rational approach to combined targeting of two major transcriptional regulators, EZH2 and CDK9 in MYC-medulloblastoma
Rajeev Vibhakar
Investigate the molecular pathways regulated by the oncogenic MIC2 in driving H3K27M-DIPG tumorigenesis
Sujatha Venkataraman
Developing a Clinically Translatable Interpretable 3D Radiographic and Transcriptomic Joint Domain Deep Learning Framework for Limited Datasets Using Adamantinomatous Craniopharyngioma as an Example
Todd Hankinson
PRMT5 Inhibition in Pediatric High-Grade Glioma
Adam Green
Development of Novel Therapies for Atypical Teratoid/Rhabdoid Tumors
Jean M. Mulcahy Levy
Development of CAR T cells to target ependymoma and the tumor microenvironment
Anandani Nellan, Nicholas Foreman
Understanding the oncogenic role of BMI1 in ependymoma (EPN) PFA tumors at the single-cell transcriptional level
Sujatha Venkataraman, Andrew Donson, Nicholas Foreman, Rajeev Vibhakar
Development of Human Immune System Mouse Models of ATRTs
Siddhartha S. Mitra
Targeting Hes5 in Embryonal tumors with multilayered rosettes (ETMR)
Sujatha Venkataraman, Andrew Donson
EMT in Craniopharyngioma
Todd Hankinson
Investigation Toward a DIPG Combination Therapy Clinical Trial
Adam Green
Targeting BMI1 in AT/RT
Rajeev Vibhakar
Combinatorial Immunotherapy against High-Risk Medulloblastoma
Siddhartha S. Mitra
Tumor microenvironment (TME) Modifying Immunotherapy Combined with Tumor Neurosphere Vaccine for Pediatric High-Grade Glioma
Anandani Nellan, Adam Green, Steven Dow
Biomimetic Microenvironments to Model Leptomeningeal Metastasis in Pediatric Neuro-Oncology
Rachael Sirianni
Evaluating the Mechanism and Efficacy of Targeting the Replication Stress Pathway in Pediatric Osteosarcomas
Pankita H. Pandya
2019 Projects Funded
RNASeq “in the round”: Extension of tumor characterization to include mutational and fusion data on all new patients
Nick Foreman, Andrew Donson, Rajeev Vibhakar
Researchers will use RNA sequencing to analyze new tumors, as well as tumor samples from the last 30 years. This project will extend the analysis to identifying whether tumors result from gene mutations or fusions of existing genes. This improved characterization of tumor samples provides additional information to help determine the best treatment for each tumor.
Creation of a single-cell atlas of pediatric brain tumors
Andrew Donson, Nicholas Foreman, Todd Hankinson, Rajeev Vibhakar
High-throughput drug screening in pediatric brain tumors for rapid clinical translation
Nicholas Foreman, Katie Dorris, Andrew Donson
Pre-Clinical Modeling of drug efficacy in Pediatric Brain Tumors
Angela Pierce, Rajeev Vibhakar
High-Throughput Next Generation Sequencing and Analysis of CRISPR-Cas9 Mediated Gene Knockout Screen and Validation of Targets identified in Pediatric Brian Tumor
Sujatha Venakataraman, Rajeev Vibhakar
Targeting NTRK fusions in Diffuse Intrinsic Pontine Glioma (DIPG)
Rajeev Vibhakar, Lindsey Hoffman, Nathan Dahl
Investigation of Pediatric Treatment-Induced High-Grade Gliomas
Adam Green
Novel targeting of CD99, a cell surface protein in H3K27M-mutant DIPG
Sujatha Venkataraman, Adam Green, Siddhartha S. Mitra, Terry Fry, Rajeev Vibhakar
Using a CRISPR screen to identify genes that regulate immune surveillance by microglia and macrophages
Siddhartha S. Mitra
In vivo model targeting BMI1 in ATRT
Irina Alimova, Angela Pierce, Rajeev Vibhakar
Targeting BMI1 in neuroblastoma tumors
Sujatha Venkataraman, Rajeev Vibhakar
Understanding the oncogenic role of CDK7 and CDK12, the crucial targets identified from the shRNA screening in medulloblastoma
Bethany Veo, Rajeev Vibhakar
Analysis the Epigenome to identify novel resistance mechanisms to targeted BRAF inhibition
Jean Mulcahy Levy, Rajeev Vibhakar
Can ATR kinase inhibitors sensitize medulloblastoma tumor cells to radiation and chemotherapy treatments?
Rajeev Vibhakar
Predictive Diagnosis and Genomics of Pediatric Neurological Tumors via Convolutional Neural Networks
Todd C. Hankinson
Multiple-Biopsy of Infiltrative Glioma (M-BIG) Study
Nathan Dahl, Lindsey Hoffman, Adam Green
Development of a novel extracellular PRAME antibody to target atypical teratoid rhabdoid tumor
Anandani Nellan, Andrew Donson
Establishing DIPG xenograft models and advancing therapeutic strategy in DIPG
Sujatha Venkataraman, Siddhartha S. Mitra
In vivo animal model to investigate nanoparticle-mediated brain drug delivery
Krishna Madhavan, Rajeev Vibhakar
Development of Models of Recurrent Pediatric High-Grade Glioma
Adam Green
Study looking at feasibility of isolating circulating tumor DNA from blood, cerebrospinal fluid and urine in Pediatric Solid Tumor patients
Nicholas Foreman, Masanori Hayashi
Biomimetic Microenvironments to Model Leptomeningeal Metastasis in Pediatric Neuro-Oncology
Rachael Sirianni
2018 Projects Funded
The RNASeq transition: Creation of a pediatric brain tumor RNAseq reference database (year 2 of 2)
Andrew Donson, Nick Foreman, Rajeev Vibhakar
Through 15 years of using gene chip technology (“chipping”) to analyze tissues of brain tumor samples, The Morgan Adams lab now houses one of the largest pediatric brain tumor gene expression databases in existence. This resource is an essential reference set for state-ofthe- art diagnosis, allowing researchers to assign children’s brain tumors into newly described and clinically relevant pediatric brain tumor subgroups. RNA sequencing provides amplified data, giving researchers the unprecedented opportunity to identify the DNA mutations underlying tumor growth. Identification of tumor mutations will allow more definitive identification of tumor types so that more effective chemotherapy can be selected to specifically target these tumors.
Chipping “in the round.” Extension of tumor characterization to include mutational and fusion data on all new patients
Nick Foreman, Andrew Donson, Rajeev Vibhakar
Researchers will use RNA sequencing to analyze new tumors, as well as tumor samples from the last 30 years. This project will extend the analysis to identifying whether tumors result from gene mutations or fusions of existing genes. This improved characterization of tumor samples provides additional information to help determine the best treatment for each tumor.
High throughput next-gen sequencing and analysis of CRISPR-Cas9 mediated gene knockout system
Sujatha Venkataraman, Rajeev Vibhakar
This project will perform sequencing and analysis of different brain tumor cells based on CRISPR/Cas9 platforms from two companies. CRISPR/Cas9 is a technology that enables researchers to edit parts of the genome by removing, adding, or altering sections of the DNA sequence. (Paid for by The Adam Crocker Fund for Cancer Research.)
Pre-clinical modeling of drug efficacy in pediatric brain tumors
Angela Pierce, Rajeev Vibhakar
Development of novel drugs to treat pediatric brain tumors is often complicated by a lack of robust pre-clinical data and lab modeling of drugs. This frequently results in phase 1 clinical trials that fail. To avoid situations like this, we have established pre-clinical models of a range of brain tumors (funded by MAF in 2015) and we can test multiple drugs using this platform. These studies will leverage data from all MAF-funded research from the past 7 years to test novel therapeutics and combinations.
High-throughput drug screening in pediatric brain tumors for rapid clinical translation
Andrew Donson, Nick Foreman, Katie Dorris
This project will systematically test more than 100 FDA-approved oncology drugs on all pediatric tumor types, using an established process that allows testing to be done quickly, using tumor samples obtained from Children’s Hospital Colorado patients. Previous analysis by researchers led to the identification of novel therapeutic approaches for a patient with an Ependymal tumor.
By specifically testing FDA-approved compounds that already have known treatment effects in adults and often children, the results of testing can be rapidly applied to patients without the need for time-consuming drug development and safety testing.
Disease progression model for H3K27M-mutant DIPG: Determining downstream effects of effective treatment
Sujatha Venkataraman, Adam Green
Diffuse intrinsic pontine glioma (DIPG) are aggressive tumors at the base of the brain that typically are untreatable. In the past several years, major sequencing projects have found most of these tumors harbor a mutation in histone 3 called H3K27M, which is unique in human disease. Histones are proteins around which DNA folds and mutations in these proteins have major implications for which genes are turned on and off. We believe that a better understanding of the H3K27M mutation’s effects will allow us to target DIPG treatments against the combination of genetic changes truly driving the tumor.
The oncogenic role of the SEC in H3K27M-mutant DIPG
Nathan Dahl, Rajeev Vibhakar
This project seeks to understand secondary factors, in addition to mutations in the histone 3 gene (H3K27M), that lead to growth of the DIPG tumor. Completion of this project will bring new understanding of the mechanisms by which H3K27M mutations drive the formation of DIPGs and lay the groundwork for a novel therapeutic approach in treating these tumors.
Use of pluripotent stem cells (hiPSCs) to model DIPG cell formation and radio-resistance
Sujatha Venkataraman, Rajeev Vibhakar
This project will use stem cells to create lab models of DIPG tumors and better understand the biology of this tumor, including how tumor cells form and how they develop resistance after radiation.