News

2018 Funding 625k to Support 11 Research Projects

Monday, April 09, 2018


Doctors and Researchers of The Morgan Adams Foundation Pediatric Brain Tumor Research Program

The Morgan Adams Foundation Board of Directors has granted $625,000 to fund 11 research projects and equipment in The Morgan Adams Pediatric Brain Tumor Research Program at Children’s Hospital Colorado in 2018. This brings the total amount of research dollars we’ve funded since our inception in 2001 to more than $4.7 million dollars.

“The crucial support from Morgan Adams continues to fund all those high-risk, high-reward studies that would otherwise not be possible,” said Rajeev Vibhakar, MD, PhD and Program Leader of Pediatric Neuro-Oncology at the University of Colorado School of Medicine and Children’s Hospital Colorado. “It is these studies that often lead to novel, groundbreaking research projects and subsequent therapeutic interventions.” (Below is a summary of the research projects funded in 2018. We’ll tell you more about these projects and the equipment in upcoming newsletters.)

 

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 has been an essential reference set for state-of-the-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.)
 
Lab model to investigate nanoparticle-mediated brain drug delivery (year 3 of 3)
Krishna Madhavan, Rajeev Vibhakar
Many of the drugs used in chemotherapy to treat brain tumors perform very well in the laboratory settings, but they fail to cross the blood-to-brain barrier in direct clinical applications, meaning the chemotherapy doesn’t reach the tumor. This project will study the delivery of drugs using gold nanoparticles into brain tumor cells in lab models to evaluate the effectiveness of delivery routes and the drug dosage required to be effective.
 
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 gliomas (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. Understanding the biology of a tumor is the best way to target the tumor effectively. This will ultimately result in new therapies for DIPG patients.
 
Analysis of paired BRAF V600E mutant glioma patient samples to identify novel resistance mechanisms to targeted BRAF inhibition
Jean Mulcahy-Levy, Theodore Nicolaides
(University of California San Francisco)
BRAF V600E mutations occur in a variety of gliomas, and the development of targeted therapies has provided a new treatment option for some patients. However, research shows that these mutations are likely to develop a resistance to these therapies. This project seeks to identify molecular and pathway alterations driving resistance to BRAF V600E inhibitors in central nervous system tumors. This will provide tools to identify patients who will need additional therapies to treat their tumors.
 
Oncogenesis caused by loss of SMARCB1 tumor suppressor is dependent on the activity of SIRT2
Rajeev Vibhakar
This project seeks to determine the molecular mechanisms by which the SIRT2 gene drives atypical teratoid/rhabdoid (AT/RT) tumor progression and to provide pre-clinical validation that using the drug TM is a worthwhile therapeutic approach. It is expected that this will then progress to a phase 1 clinical trial for treating AT/RT patients.

Newsletter March 2018

Saturday, March 31, 2018

Read our March 2018 Newsletter HERE.


Sujatha Venkataraman

Sunday, December 03, 2017

After her son Rishi passed away from childhood cancer 14 years ago, Sujatha Venkataraman, PhD, was inspired to switch her research focus from adult breast and prostate cancer to childhood cancer. “Innocent kids should not go through this,” Sujatha reflects. “Kids like my little son are my inspiration.”

As a researcher of The Morgan Adams Foundation Pediatric Brain Tumor Research Program at Children’s Hospital Colorado, she is working to find a cure for DIPG – diffuse intrinsic pontine glioma – which is 100% fatal. “I am currently working on identifying the genes that cause DIPG and to identify gene pathways that make the DIPG tumor aggressive after relapse from radiation treatment.”

The typical treatment for DIPG patients is radiation, the only standard therapy so far. But, the tumor comes back after radiation, growing even more aggressively than the original tumor and becomes resistant to radiation therapy. At that point, there are no treatment options and parents are often told to take their child home to spend the limited time they have left away from the hospital.

DIPG affects children almost exclusively. Approximately 200-400 children in the United States are diagnosed with DIPG each year.

“Since very little is known about DIPG tumor biology, I want to understand the biology of this tumor. Understanding the biology of a tumor is the best way to target it faster.” Last year, Sujatha and Dr. Rajeev Vibhakar received a $20,000 MAF grant to investigate whether PTC-209, a small-molecule inhibitor of BMI1 protein, can help kill DIPG tumor cells. The research has yielded important data and resulted in more grants – totaling $500,000 – from the U.S. Department of Defense and other organizations, and that means a new possibility of hope for kids with this uniformly fatal tumor.

Only 4 percent of the national federal funding goes to pediatric cancer research, Sujatha notes. “A fraction of that money goes to pediatric brain tumor research. Most of our DIPG work is funded by The Morgan Adams Foundation.”

Watch Sujatha talk about DIPG tumors and the research she is working on in this short video.

Sujatha’s published papers related to DIPG include:


Chocolove Holiday Gift Box

Sunday, November 19, 2017


Chocolove has teamed up with The Morgan Adams Foundation to bring you an incredible gift box for the holidays. This 12-piece box of decadent dark chocolates filled with liquid caramel and dusted with real gold flakes is sure to be a hit with friends, family, co-workers and clients. Each box comes with a Happy Holidays card attached to the top.

100% of sale proceeds are donated to The Morgan Adams Foundation which funds pediatric cancer research! 

ORDER your gift box today. 

Morgan Adams's spirit lives on in the dedicated researchers and doctors we work with at the Children's Hospital Colorado. Like us, they are dedicated to finding cures for children's cancer. Children's bodies are different than adults and require different approaches to help cure. Because a child's life has just begun, there is no rationalization of how damaging a treatment can be on a child, to save a life. Every effort must be made to cure a child's cancer with the child having a full recovery and, if possible, no collateral damage so they can go on to live a long, full life.

To this end, a novel and careful drug delivery method is required. Binding drugs to gold nanoparticles is such a method being studied by Dr. Rajeev Vibhakar, Director of the Children’s Hospital Colorado Pediatric Neuro-Oncology program.

This pioneering work uses gold-coated nanoparticles as a carrier to bind and deliver cancer drugs specifically to cancer cells. This research will allow for more effective treatment with less drugs and less healthy cells being damaged and, therefore, less side effects. The research steps are several and the results so far are promising.

Chocolove's  holiday gift box of 12 decadent dark chocolates are filled with liquid caramel and dusted with real gold flakes. The 23-karat gold dust is real and so is the amazing chocolate/liquid caramel experience. The inspiration for the nano-amounts of gold dusting these chocolates is heartfelt. Chocolove will donate 100% of the proceeds for this item to The Morgan Adams Foundation! 

Happy Holidays from Chocolove and The Morgan Adams Foundation!


 


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