Children’s Brain Tumor Project Lab Update: Fall 2014

Posted in About the CBTP, Research, Updates

By Sheng Li, Ph.D. Ty Louis Campbell Fellow I am so grateful for the opportunity to work with the Children’s Brain Tumor Project as the first Ty Louis Campbell Fellow. I thank Cindy and Lou Campbell and the TLC Foundation for funding this creative position. My passion is bioinformatics and computational biology, both of which play critical roles in decoding tumors such as DIPG, gliomatosis cerebri, and AT/RT—the cancer that claimed Ty’s life two years ago. After receiving a bachelor’s degree in biotechnology from Sun Yat-sen University in Guangzhou, China, I came to Weill Cornell in 2009. I’ve been here for the past five years as a Ph.D. candidate in computational biology, during which time I have published research articles on high-throughput sequencing data analysis for cancer biology in Nature Biotechnology, Nature Genetics, Journal of Clinical Investigation, and Genome Biology. I’ve also been a lecturer in cancer genome data analysis for courses at Weill Cornell Medical College and the Institute of Computational Biomedicine’s EpiWorkshop. I completed my doctoral dissertation on the topic of cancer epigenetic dysregulation, and I’ll be further pursuing that research in this fellowship. The science of epigenetics is relatively new, and it’s emerging rapidly. The term refers to changes in the ways genes are expressed that don’t change the DNA itself. Disruptions in the epigenome are thought to play a fundamental role in how cancer develops, but how those disruptions happen are only just now starting to be understood. Because they occur spontaneously, they cannot be predicted—which is why the rare and inoperable tumors that strike children seem to come from out of the blue. There are no known risk factors, no family history, no warning signs—just a child who is healthy one day and terminally ill the next. For answers, we must comb through a staggering amount of data that can now be produced through sequencing and other studies. Today’s high-throughput sequencing methods are faster and more accurate than they were even just a few years ago, but each tumor sequenced produces an avalanche of data that must be pored over and analyzed by a bioinformatics specialist in order to find answers and draw conclusions—or at least identify new pathways for future studies. I am proud to be playing a role in the Children’s Brain Tumor Project’s multi-pronged research efforts—banking tissue for future study, sequencing tumors from a wide range of patients, interpreting the data produced from sequencing those samples, and then testing new drugs and new delivery methods selected specifically for that individual tumor. The Department of Neurological Surgery is working with the Department of Pathology, the Cancer Center, and the Center for Precision Medicine here at Weill Cornell as well as collaborating with...

Read More

Children’s Brain Tumor Project Lab Update: Summer 2014

Posted in About the CBTP, Research, Updates

By Prajwal Rajappa, M.D. Pediatric Brain Tumor Fellow Weill Cornell is one of 200 institutions that make up the Children’s Oncology Group (COG), the world’s premier organization dedicated to eradicating childhood cancer. Dr. Mark Souweidane and Dr. Prajwal Rajappa lead the Weill Cornell Pediatric Brain and Spine Center’s participation in a long-term study of brain tumor tissue samples collected from pediatric patients around the world, with the goal of understanding the molecular profile of these tumors. This lab update about our COG project was contributed by Dr. Rajappa. This COG study is extremely important given the lack of effective treatments available for pediatric brain tumor patients. We are collecting brain and spinal tumor tissue from pediatric patients treated at COG facilities around the world, providing a repository for long-term storage of those specimens. This study allows us to make specimens available to expert researchers both here in the United States and abroad who are working to understand the biology of these tumors. These repository-driven studies utilizing human tissue serve as the platform for meaningful translational research, which relies on laboratory findings that can be quickly applied to develop new treatment options. The rapidly evolving science of human genomics has the potential to change how physicians diagnose and treat cancer, but molecular studies require access to tumor tissue, which has been extremely limited—especially when the tumors are rare. There’s a particular shortage of pediatric tissue specimens available for ependymomas, thalamic gliomas, brainstem gliomas, diffuse pontine gliomas, gliomatosis cerebri, low-grade gliomas, and primary GBMs. The limited number of specimens available for research within any single institution can make it impossible to conduct statistically powerful and high-impact molecular research. Therefore, participation from multiple institutions is essential. Here at Weill Cornell, with a world-class pediatric service that draws patients from near and far, we have gathered a wide variety of samples of many pediatric brain and spine diseases in our repository, making us one of the top member institutions in the COG. In fact, in our first full year of participation in this study (2012), Weill Cornell ranked eighth out of 142 participating institutions in terms of number of pediatric patient samples enrolled. This year, we are poised for our highest patient enrollment on study. As shown in the pie chart at right, we have accrued a wide array of pediatric central nervous system (CNS) disease entities in our departmental repository that will serve as valuable material for further genomic sequencing and translational research. Within Weill Cornell, we have developed streamlined collaborations with other departments, such the department of pathology, which will ultimately advance our understanding of the biology of pediatric brain tumors and further initiate multi-disciplinary studies. Solidifying our role at COG,...

Read More

Children’s Brain Tumor Project Lab Update: Spring 2014

Posted in About the CBTP, Research, Updates

By Mark M. Souweidane, MD Co-Director, Children’s Brain Tumor Project I’ll never forget May 1, 2012 — that was the day I performed the very first procedure in a new clinical trial testing convection-enhanced delivery (CED) of a therapeutic agent in a child with DIPG. More than ten years of my prior lab work, including bench research and animal testing, had me absolutely convinced that this was a safe procedure. Still, with anything so completely new there’s just that tiny seed of doubt, the faintest whisper of “what if…” What I was not prepared for were the emotional ties that quickly took hold of me. The little girl in the OR that day was Caitlin Downing, whom I had come to love in just a few short weeks of knowing her and her family. Hugs, insightful questions, and smiles from this 5-year-old were gripping. Caitlin’s sister, Courtney, had even joined her on one of her preoperative visits to New York so that she could approve of the doctor who would offer hope. Imagine my relief when the procedure went exactly as expected, and imagine my heartbreak several months later when the tumor came back to claim Caitlin’s life. But her successful surgery validated every effort that went into this translational project and left no doubt that we should push on. Today we find ourselves in an exciting position: With 13 children treated so far (all of whom have tolerated the treatment well, with no adverse effects), we have answered critical questions about the technical, surgical, and diagnostic aspect of this drug delivery tactic. Early results have raised awareness from oncologists, neuro-surgeons, radiologists, and pharmacologists from all over the world. The momentum is building rapidly. So encouraging are the results that we have decided to request a continuation of the study. If the continuation is approved, we will plan to treat a minimum of 12 more children at escalating doses. The study is being positively viewed on a national level. The preliminary results of this trial were presented to the Pediatric Brain Tumor Consortium (PBTC) in Atlanta last month. That group is highly interested in moving the strategy into a “group-wide” study and has assembled a working group, which I am leading, to formulate the best plan. Even as we modify the current strategy, we are continuing our laboratory and clinical efforts in different arenas. As an example, we are using other strategies for bypassing the blood-brain barrier, which is what prevents us from getting adequate doses of cancer-fighting molecules to a tumor site. In addition to testing CED, we are also pursuing another potential route, using super-selective intra-arterial chemotherapy to deliver medicine directly into the blood vessels of the...

Read More

Remembering Allie Fisher

Posted in Children's Brain Tumor Project Families

Kyle and Kelly Fisher of Overland Park, Kansas, became reluctant members of the Children’s Brain Tumor Project this summer, when they lost their three-year-old daughter, Allie, to gliomatosis cerebri. Allie passed away less than three months after her first seizure, so her family was still reeling from the shock of her diagnosis at the time of her death. Still, they donated Allie’s tumor to the Children’s Brain Tumor Project to help advance the science and lend a hand in the fight against gliomatosis cerebri and other terrible tumors. The Fishers’ community came together in love and support and held a neighborhood fundraiser called “Allie’s Garage Sale,” which they hope will become an annual event to support the Children’s Brain Tumor Project. Allie’s dad, Kyle, says, “We loved the three short years we had with her and miss her dearly. It brings us great joy to see the positive impact Allie had on people and is continuing to have via her tissue donation and fundraising for the Children’s Brain Tumor Project. We are hoping that the $4,500 raised via Allie’s Sale is only the beginning.” All of us at Elizabeth’s Hope and the Children’s Brain Tumor Project mourn Allie’s loss and welcome the Fishers and their friends and family to what one mom recently called “the worst club in the...

Read More

Children’s Brain Tumor Project Lab Update: December 2013

Posted in About the CBTP, Research, Updates

By Jeffrey Greenfield, MD, PhD Director, Children’s Brain Tumor Project It’s hard for me to believe that two years have gone by since Elizabeth’s Hope was born, allowing us to launch the Children’s Brain Tumor Project. In scientific research terms, this has been the blink of an eye. I am so very grateful for your support—this truly is a dream come true for me, and some day we will be able to make a significant impact on the care of children facing brain tumors. Anniversaries always make you look back and think about where you’ve been, and our list of accomplishments over the past two years is considerable. Here are some of the highlights of our first two years: 2011-2012 Elizabeth’s tumor was the very first sample of gliomatosis cerebri ever subject to genomic analysis, and it yielded a treasure trove of information about the genetic mutations associated with her tumor. Since then we have been able to sequence several additional tumors, searching for what they have in common with Elizabeth’s, and where they diverge. This hunt for patterns and data is what will help us unlock the mystery of this rare tumor. Only weeks after Elizabeth’s Hope was founded, my colleague Dr. Mark Souweidane received FDA approval to begin a groundbreaking trial testing the safety of convection-enhanced delivery (CED) of therapeutic agents for pontine gliomas (DIPG). He treated the first patient in May of 2012 and has treated eight more children since then, with zero toxicity. Testing different agents, at different doses, will generate the data we need in the coming months and years. In the fall of 2012, a basic science researcher named C. David Allis, Ph.D., was investigating and documenting a DNA histone called H3.3. Much to everyone’s surprise, it was discovered that H3.3 mutations are found in pediatric gliomas. Dr. Allis and I are now collaborating on a new project to try to find out why the mutation causes gliomas — including gliomatosis cerebri — to develop. I was honored to share in a Starr Cancer Consortium grant given to Dr. Allis to pursue the research. I have a two-year, $112,000 grant for 2013 and 2014. 2013 In January 2013, the Institute for Precision Medicine opened its doors at NewYork-Presbyterian/Weill Cornell Medical Center. This cutting-edge research hub is exploring how to develop optimal targeted, individualized treatment based on each patient’s genetic profile. This is extraordinarily significant for Elizabeth’s Hope and the Children’s Brain Tumor Project, as it brings the ability to sequence tumors right onto our campus and spares us the cost of buying new machinery. Our gifts can be used for the bioinformatics staff members we need to interpret the data, rather than on...

Read More

Children’s Brain Tumor Project Lab Update: Fall 2013

Posted in About the CBTP, Research, Updates

By Jeffrey Greenfield, MD, PhD Director, Children’s Brain Tumor Project We have some extremely exciting news to report this month: Yujie Huang, PhD, of our Children’s Brain Tumor Project laboratory, has been awarded a three-year, $400,000 grant from the Department of Defense. Dr. Huang was awarded the grant for a project called “Characterizing and Targeting Bone Marrow-Derived Inflammatory Cells in Driving the Malignancy and Progression of Childhood Astrocytic Brain Tumors.” Gliomatosis cerebri is one of the most difficult — if not the most difficult — to cure of all astrocytic brain tumors, so getting this project funded is a significant step forward for us. News like this makes it more and more clear how critical the support of Elizabeth’s Hope is to us. Department of Defense grants are not easy to secure, and an award of this size required us to file an application with supporting data based on previous research. That data assures the DoD that its grant money is going to projects that are based on sound science and have good chance of success. How could our lab have done the foundational work, and generated the data, if not for you, our loyal supporters? Even more exciting, some of the data used in support of this grant application was generated by Emma Vartanian, who joined the lab on a summer fellowship from the Saint Baldrick’s Foundation. As you may recall from our Spring 2013 newsletter, Emma’s project uses mouse models to study the effects of an inhibitor drug on gliomas, with the goal of preventing low-grade tumors from progressing into fatal ones. If we can learn how to stop bone marrow cells from signaling the distant tumor to grow, we may be able to keep low-grade gliomas from developing into high-grade tumors like gliomatosis cerebri. Under Dr. Huang’s guidance this summer, Emma and the team initiated the transplant phase of the study and performed bone marrow transplants on more than 20 animals. Now those mice will be treated with an experimental inhibitor drug to test its ability to limit tumor growth. As the treatment progresses in Dr. Huang’s newly funded phase of this study, our research team will be able to analyze how the transplanted bone marrow-derived cells move and participate in tumor progression. We already have histological and radiographic data, in the form of brain tissue slides and MRI images, suggesting far better tumor outcomes and survival patterns in drug-treated transplant mice, as compared to untreated control animals. This is exciting stuff indeed. I am so energized by how our work is all coming together. With Elizabeth’s Hope making our lab work possible, we gave St. Baldrick’s the confidence to award us the summer fellowship. With...

Read More