News

RESEARCHER SPOTLIGHT Adam Green, MD

Monday, April 23, 2018

Dr. Adam Green joined the neuro-oncology group at Children’s Hospital Colorado in 2014. He has a dual role – caring for patients at Children’s Hospital Colorado in the pediatric neuro-oncology department and conducting research for The Morgan Adams Foundation Pediatric Brain Tumor Research Program. His goal is to develop better treatments, and ultimately a cure, for rare brain tumors that have low survival rates. Diffuse Intrinsic Pontine Glioma (DIPG), which has a 0% survival rate, is at the top of his list. The tumor is rare: about 200 patients, mostly between the ages of five and nine, are diagnosed each year in the U.S. The sole treatment option for DIPG is radiation, which only serves to slow the tumor’s progression, not stop it.
 
WHY STUDY DIPG?
I planned to become a pediatrician when I was in high school and I was a neurobiology major in college. I became interested in pediatric brain tumors in medical school and then specifically in DIPG because of a patient I treated during my first year of fellowship. It felt unacceptable to me that we still have a disease in our field for which we can offer patients and families no hope for cure, unlike every other cancer we treat. I felt compelled to try to change this through research.
 
RESEARCH FOCUS:
In my work on DIPG to this point, we have used cell culture and lab models of the disease, created directly from patient tumor samples, to identify new weaknesses in these tumors and try to exploit those weaknesses through new treatments. We have been able to bring two of these treatments into clinical trials.
 
GETTING CHEMO TO THE TUMOR:
One trial is designed to determine whether chemotherapy delivered orally or by IV can penetrate to DIPG tissue enough to have an effect. The trial arose from work conducted in our lab as part of The Morgan Adams Foundation Pediatric Brain Tumor Research Program and is currently expanding to other hospitals. The trial will help us decide whether we should continue to investigate new medicines delivered by these routes or focus on delivering chemotherapy directly to the tumor. I am confident we’ll be able to answer this question.
 
ONE TRIAL COMING UP:
Dr. Green and his colleagues will present findings from this clinical trial at the International Symposium on Pediatric Neuro-Oncology, taking place this July in Denver.

 


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.


You can help kids with cancer RIGHT NOW

Tuesday, December 12, 2017

Our young friend Cooper knew research was being done on rare types of kids' brain tumors. He knew that research took money. So when doctors explained last April that his hope for remission was gone, the bright 12-year-old had an idea: he would use his life savings to find a cure.

If only it were that simple. If only the dollars Cooper had saved for college could have made that happen. If only diffuse intrinsic pontine glioma, or DIPG, weren't the deadly pediatric brain cancer it is. If only the answers had been found before it claimed his life.

After Cooper passed, Sujatha Venkataraman, PhD - one of the researchers working closely with The Morgan Adams Foundation (MAF) - told his parents that targeting DIPG is her "only mission and focus in life." "I lost my own small son Rishi to cancer," Venkataraman reflects. "Kids should not go through these sufferings. DIPG is under-researched and it is always fatal. We are working hard to find a way to improve outcomes for these children."

Childhood cancer is scary. Some types remain 100% fatal. But there is hope.

Last year, Sujatha and Dr. Rajeev Vibhakar received a $20,000 MAF grant to identify drug therapies that may slow DIPG tumor growth. This research has yielded important data and resulted in more grants - totaling $500,000 - from the federal government and other organizations, and that means a new possibility of hope for kids like Cooper.

You have made this possible.Your gift starts the process of getting good ideas out of the lab and into tangible treatment options for kids and teenagers.

Your continuing support will help doctors and researchers pursue every possible new treatment avenue for kids with cancer. The hope you give these kids will be leveraged many times over. I invite you to join me in continuing our work to create a brighter future for kids and teens battling cancer.

With much gratitude,

 

Founder and Executive Director



Remembering Trevor

Trevor Kling was very involved as a Morgan Adams Foundation Ambassador. A shining light among us, this 14-year-old Honor Roll student missed only one day of school while enduring 36 radiation treatments and 14 months of chemotherapy. He passed in October, more than two years after his diagnosis with anaplastic astrocytoma grade III.

Trevor's dad Dave shares, "When his mom Cheryl and I explained to Trevor that he was dying, he told us he still wanted to fight for other kids. He knew being an Ambassador would help make more money to fund more research, even if it couldn't help him. So, we're going to continue that, because it will make a difference for someone 10 years down the road."

The outlook for kids with Trevor's type of cancer has changed little. Your gift can help move the needle on the translational research needed to change the survival rates for kids battling highly aggressive brain tumors.

Please give generously.





By shining laser light on cancer cells, researchers at The Morgan Adams Foundation Pediatric Brain Tumor Research Program are able to track the effect of promising cancer drugs. "We use a variety of lasers, not for making things happen, but for detecting what is happening in our cancer cells," explains pediatric hematologist-oncologist Dr. Rajeev Vibhakar. "With our imaging flow cytometer, we can detect individual cells, which allows us to learn more from very small samples. The cells are treated with dyes, so that - depending on the laser we shine on them - the light reflected is different. This allows us to tell if the cell is dying - a process called apoptosis - or alive."

Anti-cancer drugs trigger apoptosis in cells that are diseased. Dr. Vibhakar says, "A lot of the research funded by The Morgan Adams Foundation focuses on drugs currently available for the adult population. We want to find new 'targets' for these existing drugs in the pediatric population." When you support this work, your gift helps us fund ways to get new treatments to kids with cancer faster than the decade or more required for most drug development.

Through your gift, you can help make this happen. In this lab. At this time. Thank you for shining a light on new treatment possibilities for kids with cancer.


"This program is the cutting edge."

 

A neuro-oncology program led by world-class researchers, Dr. Rajeev Vibhakar and Dr. Nick Foreman. A lab producing and documenting breakthrough results. And a promise to stay on the leading edge of finding a cure for pediatric brain cancer. Those energies merged in September at the naming of The Morgan Adams Foundation Pediatric Brain Tumor Research Program. Board Chair John Dudasch recalled his daughter's fight: Avery died at the age of 11 after an 11-month battle with a diffuse high grade glioma. He noted, "These aren't just nameless kids we are asking you to work for. Cancer strikes everywhere. You can help us make a difference."

Please join the Dudasch family in supporting the vital work being done in this dedicated lab. Every gift will be multiplied - in research, results, kids healing, and our infinite hope for a cure.



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:


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