In the traditional funding model, researchers cannot be nimble. If their research leads them to a new and important finding, they cannot redirect funds from other grants to pursue this promising information.
This is where Unravel comes in. Our goal at Unravel is to eliminate obstacles, bottlenecks, and barriers by providing unrestricted funding to help researchers translate ideas into new therapies. We do not ask researchers to take hours to write a grant. We select the best researchers knowing they are working tirelessly to find new, less toxic therapies for the children they are treating and their families.
We have created a Scientific Review Committee compiled of current pediatric research scientists, members of a pediatric research consortium, pharmaceutical industry scientists, and/or clinical trials coordinators. These individuals are in place to help us to identify pediatric cancer scientists with promising work that we can fund.
As a physician-scientist, Dr. Olson cares for children with brain tumors and conducts research that focuses on discovering and developing new cancer therapies. His lab’s work has led to more than a dozen national clinical trials, of which he leads a Phase III trial through the Children’s Oncology Group. Dr. Olson is the founder of Presage Biosciences and Blaze Bioscience.
His lab invented the chlorotoxin-based Tumor Paint, which led to the development by Blaze of the clinical candidate Tozuleristide (BLZ-100), now in human trials. He authored “Clinical Pharmacology Made Ridiculously Simple,” which has been the most used pharmacology board review book for more than 25 years.
Dr. Olson earned his Ph.D. in Pharmacology in 1989 and his M.D. in 1991, both from the University of Michigan. He then completed his residency in pediatrics in 1994 and his fellowship in pediatric oncology in 1997, both at the University of Washington. Dr. Olson is currently a Full Member at the Fred Hutchinson Cancer Research Center, a Professor at the University of Washington, and an Attending Physician at Seattle Children’s Hospital.
The Monje Lab studies the molecular and cellular mechanisms of postnatal neurodevelopment. This includes microenvironmental influences on neural precursor cell fate choice in normal neurodevelopment and in disease states. Areas of emphasis include neuronal instruction of gliogenesis, cellular contributions to the neurogenic and gliogenic signaling microenvironment, molecular determinants of neural precursor cell fate, and the role of neural precursor cells in oncogenesis and repair mechanisms.
As a practicing neurologist and Neuro-oncologist, Dr Monje is particularly interested in the roles for neural precursor cell function and dysfunction in the origins of pediatric brain tumors and the consequences of cancer treatment. As a paradigm of pediatric gliogenesis, we have been focusing on brainstem tumors, whose spatial and temporal specificity bespeak an underlying developmental cause.
I would like to extend my deepest gratitude to Unravel Pediatric Cancer for the continued support of my pediatric brain tumor research program. The unrestricted funding has given us the freedom over the past year to explore new approaches for the treatment of pediatric medulloblastoma and resulted in the development of a novel drug delivery platform to get drugs past the blood-brain barrier, a major challenge in cancer research. We believe that this nanoparticle delivery system has tremendous potential for the treatment of pediatric brain tumors by utilizing lower drug doses to minimize toxicity, yet maintain or enhance efficacy, and thus improve the lives of children afflicted with cancer.
One of the major issues in pediatric cancer is when a tumor relapses or recurs for which additional treatments often result in additional toxicity to the child, however with minimal benefit in the treatment of the cancer. The continued unrestricted funding through Unravel Pediatric Cancer is allowing us to explore combination drug therapies using our nanoparticle drug delivery system to target the remaining cancer cells that remain after initial radiation and chemotherapy. We are very hopeful that this strategy will allow us to minimize or prevent tumor relapse or recurrence, the worry that every patient and their family has to endure following their initial diagnosis of cancer.
Dr. Marie Bleakley is a pediatric hematologist-oncologist who specializes in hematopoietic (blood-forming) stem cell transplantation for patients with leukemia and other blood cancers.
Her research goal is to develop novel therapies that can optimize the cancer-fighting power of immune T cells while reducing a potentially dangerous side effect known as graft-vs.-host disease, or GVHD.
Dr. Bleakley and her team have already pioneered one novel transplantation approach that selectively removes donor T cells that might cause GVHD. They are also genetically engineering T cell therapies that target unique markers to kill a patient’s cancer cells even more effectively.
Burkitt lymphoma is a highly aggressive cancer which predominantly occurs in children. The treatment for Burkitt lymphoma is high dose, intensive chemotherapy. Although up to 90% of children will be cured with chemotherapy, for children whose disease relapses, the chances of survival are less than 20%. We simply have no good treatment options for these children who slip through the cracks and relapse after chemotherapy. Our lab works to identify novel treatment approaches which may be more effective and less toxic than traditional chemotherapy.
We specifically study the genetics and the biology of Burkitt lymphoma with a focus on changes in the tumor that could be targeted with new therapies. Through generous donations of tumor samples from children with Burkitt lymphoma, we have identified genetic changes in Burkitt lymphoma and that might lead to targeted therapies. One pathway we have studied is targeting a protein called Hsp90. We found that targeting this protein in Burkitt lymphoma cells results in cell death, in part through inhibition of a signaling pathway called PI3K (Giulino-Roth et al, Molecular Cancer Therapeutics, 2017). Inhibitors of PI3K are now being studied in a pediatric clinical trial through the Children’s Oncology Group. This trial includes children with Burkitt lymphoma.
"My career is dedicated to the care of children with central nervous system (CNS) tumors and specifically the study of diffuse intrinsic pontine glioma (DIPG) and diffuse midline glioma, H3 K27M-mutant (DMG). During my pediatric oncology fellowship with Drs. Elizabeth Raetz and Bill Carroll, my labwork led to a COG clinical trial and an ASPHO’s Young Investigator Early Career award. Next, I completed a pediatric neuro-oncology fellowship at Stanford University, where I continued as a post-doc in Dr. Michelle Monje’s neuroscience/DIPG Lab. There, I helped to identify combinatorial epigenetically-targeted drug strategies in DIPG that was published in Cancer Cell and provided the preclinical foundation for a phase 1 clinical trial. In 2016, I joined the faculty at Seattle Children’s where, under Drs. Mike Jensen and Julie Park, I serve as the CNS CAR T cell Lead, helping to oversee one of the largest pediatric CNS CAR T cell programs in the world. I am the PI of two Phase 1 locoregional clinical trials using CAR T cells: BrainChild-01 targeting HER2 in children with a recurrent/refractory HER2-positive CNS tumors and BrainChild-03 targeting B7-H3 in children with recurrent/refractory CNS tumors and DIPG, the first trial to deliver intra-CNS CAR T cells to a child with DIPG.
In my lab within the Ben Towne Center for Childhood Cancer Research at Seattle Children’s Research Institute, we focus on creating treatment-naïve biopsy-derived patient-derived DIPG models to learn how to target DIPG’s molecular and immunologic vulnerabilities. Our team also optimizes CAR T cell therapies for pediatric CNS tumors and translates these findings into truly biology-driven clinical trials aimed at improving outcomes for affected children.
Cancer is the most common genetic disorder and affects 1 in 300 children. Cancers are thought to occur as a result of DNA changes that are either inherited or acquired throughout an individual’s lifetime. Advances in sequencing technologies, genome science and bioinformatics finally provide us with the tools to identify these changes and develop precision therapies to attack cancer cells while sparing their normal counterparts. While cancer genomics has entered clinical practice for both pediatric and adult cancer patients, current methods of clinical genomic data analysis are largely limited to the detection of coding mutations, and do not work well for most pediatric cancer patients. To address this, we launched the Treehouse Childhood Cancer Initiative, focusing on the study of tumor RNA as readout of both genetic and epigenetic changes that can drive pediatric tumors. The goal of Treehouse is to increase the number of pediatric cancer patients that benefit from the genomic characterization of their tumor.
We would like to extend our approaches to the study of constitutional genetic diseases, such as structural birth defects. We will use molecular biology, genomic and bioinformatics techniques to understand the etiology of these diseases and identify novel molecular targets for treatment.
I am a pediatric oncologist whose specialty is neuroblastoma. We’ve made significant progress in improving the outlook for many children newly diagnosed with this challenging disease, and we are now able to achieve the best cure rates. For those whose disease returns, we are devising new approaches that are showing encouraging results.
I feel privileged to work as part of a team that sees more patients with neuroblastoma than virtually any other institution. Our exposure to so many patients from so many varied backgrounds and parts of the world affords us an extraordinary amount of experience and knowledge that we draw on each time we meet a new patient. Our team discusses each patient’s unique situation and tailors an individualized plan of care with the greatest chance of success.
We have also learned that in some cases, neuroblastoma disappears on its own, with little or no treatment. We are identifying factors that may predict which patients will experience such spontaneous regression and which patients require more intensive therapy. In addition to patient care and research, I teach fellows and residents.
It is awe-inspiring to see young adults trying to maintain their normal lives while going through cancer treatment. The parents of our patients are also an inspiration; anything we can do for them as doctors and friends is well worth the effort.
Unravel Pediatric Cancer has generously supported the work of Dr. Nai-Kong Cheung, who is studying a vaccine for neuroblastoma as a treatment to prevent relapse of the disease. The vaccine, which was developed at Memorial Sloan Kettering Cancer Center nearly 10 years ago, works by triggering an immune response against the cancer. The MSK-initiated Phase I/II trial for high-risk stage 4 neuroblastoma patients, funded in part by Unravel Pediatric Cancer, has so far accrued nearly 300 patients. The results are highly encouraging—especially in those who had already suffered a relapse of disease prior to entering the study. Recently, the team has initiated the drafting of a new treatment protocol to increase the effectiveness of vaccine therapy. They are also exploring in-depth the impact of a patient’s intestinal flora on his/her immune response during vaccine treatment.
This work would not be possible without friends like Unravel Pediatric Cancer, and we are so grateful for your continued generosity.
Dr. Hong's research focuses on high risk solid tumors (e.g. kidney cancers, soft tissue sarcomas and brain tumors). These cancers represent the areas of greatest need in Pediatric Oncology. His work uses functional genomic techniques (e.g. RNAi, CRISPR-Cas9) and the latest sequencing technologies (e.g. long range phased sequencing, scRNAseq, ATACseq) to identify new therapeutics and mechanisms in pediatric cancers.
"As a fellow in pediatric oncology nearly a decade ago, I had the privilege of caring for several kids with ATRT. Their stories stayed with me as I became more involved in research. Throughout my research, I kept returning to SMARCB1, the protein lost in ATRT and as a result, I have been looking for ways to therapeutically target cancers that have SMARCB1 lost. One of our recent efforts are to identify novel ways we can understand the interaction between ATRTs with the immune system and trying to develop the model systems to study this in the lab."
For more info on Dr. Hong's research, click here.
Dr. Warren is an internationally recognized expert in pediatric neuro-oncology. She was appointed Clinical Director of Pediatric Neuro-Oncology at Dana-Farber/Boston Children's in 2019 and was previously Senior Investigator and head of the Neuro-Oncology Section in the Pediatric Oncology branch of the National Cancer Institute where she worked for more than 25 years. Her major focus is developing new therapeutics to improve the outcome and quality of life for children with CNS tumors. Her work focuses on rational, pharmacokinetic-based drug development for children with brain tumors, and she is a leading innovator in developing new means of drug delivery. Her clinical trials have led the field in exploring new approaches for the treatment of children with these diseases. Dr. Warren has extensive experience in pharmacology, neuro-imaging, and clinical trial design and incorporates each of these into her research. She has led a number of clinical trials, including single institution, multi-institution, national consortium, and international trials.
Dr. Warren currently serves as the chair of RAPNO (Response Assessment in Pediatric Neuro-Oncology), a member of the NCI Brain Malignancy Steering Committee, NCI Clinical Trials, and Translational Research Advisory Committee Ad hoc Working Group on Glioblastoma, and is a steering committee member for the DIPG Registry. She has served on numerous national and international scientific committees and advisory boards.
For more info on Dr. Warren, click here.
The white matter infrastructure of the brain depends on the function of a stem cell-like group of cells called oligodendrocyte progenitor cells (OPCs) that form an insulation called myelin around the long nerve fibers (much like wires) that connect electrically active brain cells. The Monje-Deisseroth research group has recently shown that more active neural circuits become better myelinated such that brain circuits used more function better. The molecules that mediate this adaptive effect of active brain cells on the behavior of OPCs is not yet well understood. One molecule, known to be expressed more in active brain regions, that modulates the behavior of OPCs during development or after certain forms of brain injury to promote growth and regeneration of myelin is called brain-derived neurotrophic factor (BDNF). Anna’s project seeks to understand if BDNF regulates activity-dependent OPC proliferation and myelin growth in the healthy brain and if medicines that mimic BDNF could be used to promote regeneration after white matter injury.
For more info on the Monje Lab at Stanford, click here.
Dr. Koldobskiy is an Assistant Professor of Pediatric Oncology and Pediatric Neuro-Oncology at the Sidney Kimmel Comprehensive Cancer Center. He received his B.S. and M.S. from Yale University and M.D./Ph.D. in the Medical Scientist Training Program at Johns Hopkins, conducting his thesis research with Dr. Solomon Snyder in Pharmacology and Molecular Sciences. He completed his Pediatrics residency training at Johns Hopkins and his Pediatric Hematology and Oncology fellowship training in the joint Johns Hopkins/National Institutes of Health program. He studies epigenetic variability in childhood cancer.
To learn more about the lab click here.
For Dr. Koldobskiy's bio page click here.
Creates mouse models and patient-derived xenograft cell lines for metastatic osteosarcoma, Ewing sarcoma, and rhabdomyosarcoma, and studies the mechanisms for development, progression, metastasis and resistance to treatment for those diseases. Most lab work is focused on using the mouse models and cell lines developed in house to test potential therapeutic strategies before passing along the data to clinical trialists. Has junior faculty, postdocs and grad students, some of whom are studying underlying molecular mechanisms of tumor establishment and progression. The mouse models are unique in that they are wild type, not immunocompromised, but growing the tumors. He makes his cell lines available to colleagues.
To learn more about the lab click here.
Dr. Yustein Bio click here.
Alia Merla, PhD. Unravel’s Scientific Review Committee Chair
Jaclyn A Biegel, PhD, Division Chief of Genomic Medicine and the Director of the Center for Personalized Medicine in the Department of Pathology and Lab Medicine at Children’s Hospital Los Angeles. Professor of Clinical Pathology at the Keck School of Medicine at the University of Southern California.
Jay Sarthy MD, PhD. Acting Assistant Professor, University of Washington School of Medicine, Attending Physician, Seattle Children’s Hospital, Research Associate, Fred Hutchinson Cancer Research Center.
Judy Davie, Associate Professor in the School of Medicine at Southern Illinois University at Carbondale
Katherine E. Warren, MD. Clinical Director, Pediatric Neuro-Oncology. Dana-Farber/Boston Children’s Cancer and Blood Disorders Center Boston, MA
Dr. Lisa Roth. Assistant Professor in the Departments of Pediatrics and Medicine at Weill Cornell Medicine. Director of the Adolescent and Young Adult Lymphoma Program at Weill Cornell Medicine/New York Presbyterian Hospital
Michelle Monje, MD, PhD. Associate professor of Neurology and Neurological Sciences at Stanford University. Scientific director of the Stanford Center for Childhood Brain Tumors.