B+ Research GrantsThe Andrew McDonough B+ Foundation is proud to announce the recipients of the Fall 2017 Research Grant Cycle. A total of $1,500,000 was awarded across 10 two-year grants of $75,000/year. Please see below for a list of the awardees.
The Andrew McDonough B+ Foundation is humbled and appreciative to have such a distinguished panel of world-class pediatric oncology clinicians and researchers on The B+ Foundation Scientific Advisory Board. Upon the recommendations of this esteemed group, The B+ Foundation looks forward to continuing to play a very active role in funding cutting-edge childhood cancer research.
Scientific Advisory Board
The members of The B+ Foundation Scientific Advisory Board are:
Dr. Peter C. Adamson
Peter C. Adamson, MD is Chair of the Children’s Oncology Group (COG), a National Cancer Institute (NCI) supported international consortium of more than 220 childhood centers that conducts clinical-translational research, including phase 1, 2 and 3 clinical trials, in children with cancer. He is Professor of Pediatrics and Pharmacology of the University of Pennsylvania School of Medicine at The Children’s Hospital of Philadelphia. Dr. Adamson is Board Certified in both Pediatric Hematology/Oncology and in Clinical Pharmacology. He is an internationally recognized leader in pediatric cancer drug development, having served until 2008 as Chair of the COG’s Developmental Therapeutics Program. Prior to becoming Chair of the COG, Dr. Adamson served as Director for Clinical and Translational Research at The Children’s Hospital of Philadelphia. His laboratory focuses on the clinical pharmacology of new drugs for childhood cancer. In June 2015, Dr. Adamson was appointed by President Obama to be a Member of the National Cancer Advisory Board.
Dr. Andy Kolb
Andy Kolb, MD received his undergraduate education at the University of Pennsylvania and his medical degree from Jefferson Medical College. After a residency in pediatrics at St. Christopher’s Hospital for Children, Dr. Kolb completed his fellowship training at Memorial Sloan-Kettering Cancer Center. He now serves as the Director of the Nemours Center for Cancer and Blood Disorders in Wilmington, DE. Dr. Kolb is a clinician scientist primarily focused in the laboratory and in the clinic on the efficient and effective translation of novel therapies into children. He is a founding member of the National Cancer Institute funded Pediatric Preclinical Testing Program and has successfully completed preclinical evaluations of numerous compounds and aided in the translation of these agents into clinical trials. In exploring the mechanism of action of targeted compounds, Dr. Kolb has developed an expertise in proteomics and cell signaling. Dr. Kolb serves within the Children’s Oncology Group (COG) as Chair of the Myeloid Disease Committee, Member of the Scientific Council, and Member of the Bone Tumor Committee. Through this work, Dr. Kolb has also developed expertise and experience in collaborative science, resource stewardship, clinical research development, clinical trial design and implementation, and in the necessities of young investigator development.
Dr. Julie R. Park
Julie R. Park, MD is attending physician at Seattle Children’s Hospital, professor in pediatrics at the University of Washington School of Medicine and associate in the Clinical Research Division at Fred Hutchinson Cancer Research Center (FHCRC). She is director of the pediatric hematology-oncology fellowship at the University of Washington.
Dr. Park is an active member of the Children’s Oncology Group Consortium and as chair of the COG Neuroblastoma Scientific Committee provides leadership for the development of neuroblastoma clinical research within COG. Dr. Park’s primary research focus has been investigating novel therapies for the treatment of high-risk neuroblastoma, a rare but aggressive form of childhood cancer. She has conducted a multi-center clinical trial to determine the feasibility and toxicity of a novel induction chemotherapy regimen for high risk neuroblastoma and has collaborated with local and national investigators to optimize the use of radiation therapy as part of treatment for neuroblastoma. Dr. Park’s work has led to her development of the current national randomized phase III trial within COG for treatment of newly diagnosed high-risk neuroblastoma.. Dr. Park has ongoing collaborations with Dr. Michael Jensen and is currently the primary investigator on an early phase clinical trial that uses adoptive immunotherapy approaches to treat neuroblastoma. Dr. Park also leads the Advanced Therapeutics Program at Seattle Children’s Hospital and has steered Seattle Children’s into becoming a leading participant in the Phase I Consortium of COG and the New Approaches to Neuroblastoma Therapy Consortium. She has been actively involved in the development of novel chemotherapeutic agents that may block critical tumor cell pathways necessary for tumor cell growth and survival.
Dr. Todd Druley
Todd Druley, MD, PhD is a board-certified pediatric hematologist/oncologist and Assistant Professor of Pediatrics, Developmental Biology and Genetics at Washington University School of Medicine. He obtained a BS in Cell and Structural Biology and a minor in Chemistry from the University of Illinois. He then completed the MD/PhD program at the University of Illinois, where he studied mechanisms of chemotherapy resistance. In 2002, Dr. Druley joined Washington University as a pediatric resident and has remained; completing his fellowship in Pediatric Hematology and Oncology and joining the faculty in 2008. He is a member of the Children’s Oncology Group (COG) Myeloid Disease Committee and Epidemiology Committee. Research in the Druley Lab is based on characterizing the link between abnormal human development and early childhood cancer, particularly infant leukemia. The lab has a track record for genomic methodology development and is currently applying that technology with the COG to improve molecular diagnostics in pediatric AML. Clinically, Dr. Druley is focused on pediatric cancer predisposition and serves as the co-director of the Pediatric Cancer Predisposition Program at St. Louis Children’s Hospital.
Dr. Michael Jensen
Michael Jensen, MD is director of the Ben Towne Center for Childhood Cancer at Seattle Children’s Research Institute and professor of hematology-oncology at the University of Washington School of Medicine. He is member of the clinical division in the Program in Immunology at Fred Hutchinson Cancer Research Center (FHCRC). Jensen holds the Janet and Jim Sinegal Endowed Chair in Pediatric Solid Tumor Research in Honor of Korey Rose.
Dr. Michael Jensen graduated from the University of Pennsylvania School of Medicine then completed training in Pediatric Hematology and Oncology at the University of Washington/Fred Hutchinson Cancer Research Center. His laboratory work began under the mentorship of Dr. Philip Greenberg, Program Head in Immunology, FHCRC and focused on the immunobiology of tumor-specific T-cells. Following completion of his fellowship, Dr. Jensen joined the faculty at the City of Hope National Medical Center where he built a translational research program integrating gene therapy and cellular immunotherapy for cancer. This program grew in to the Department of Cancer Immunotherapeutics & Tumor Immunology within the Beckman Research Institute and was incorporated into the institution’s NCI-Comprehensive Cancer Center as the Cancer Immunotherapeutics Program with Dr Jensen as its leader. During his tenure at City of Hope, Dr Jensen’s research program placed a strong emphasis on bench-to-bedside translational research and resulted in seven FDA-authorized Investigational New Drug Applications covering first-in-human applications of adoptive transfer of genetically engineered T-cells having re-directed tumor specificity for lymphoma, neuroblastoma, and malignant gliomas. In 2010, Dr Jensen joined the University of Washington School of Medicine faculty as a Professor of Pediatrics and is the founding director of the Ben Towne Center for Childhood Cancer Research. Dr. Jensen is an Adjunct Professor of Bioengineering and Neurological Surgery at the University of Washington School of Medicine and a Joint Member of the Clinical Research Division at Fred Hutchinson Cancer Research Center. Dr. Jensen is an Associate Head of the Immunology and Vaccine Development Program of the UW-FHCRC Cancer Consortium and is a SU2C Dream Team Principal Investigator on the recently awarded Pediatric Cancer Research Immunogenomics Dream Team award.
Dr. A. Thomas Look
A. Thomas Look, MD, is a Professor of Pediatrics at Harvard Medical School and Vice Chair for Research in the Department of Pediatric Oncology at the Dana-Farber Cancer Institute, as well as co-leader of the Dana-Farber/Harvard Cancer Center’s Leukemia Program. Over the past three decades, Dr. Look has published multiple peer-reviewed papers about the molecular basis of cancer and the application of molecular genetic findings to improve the treatment of childhood malignancies, particularly T-cell acute leukemia, myelodysplastic syndrome and neuroblastoma. He moved from St Jude Children’s Research Hospital to Dana-Farber Cancer Institute in 1999 specifically to establish a research program in the zebrafish model, to conduct genetic studies aimed at the identification of novel targets for cancer therapy, and he is now internationally recognized as a leader in this field.
His initial work led to the first transgenic model of leukemia in the zebrafish, paving the way for small-molecule drug and targeted genetic modifier experiments in a vertebrate disease model. More recently, his laboratory has developed the first zebrafish transgenic model of childhood neuroblastoma, opening up the opportunity to apply the powerful genetic technology available in the zebrafish to identify new molecular targets for therapy in this devastating childhood tumor.
He is the principal investigator on several NIH-funded grants, including a Program Project focusing on T-ALL pathogenesis. He has won numerous awards, including the Allison Eberlein Award for Childhood Leukemia Research, the Award for Excellence from the American Academy of Pediatrics, the Pediatric Oncology Lectureship of the American Society of Clinical Oncology, the ASPHO Frank A. Oski Memorial Lectureship Award of the American Society of Pediatric Hematology and Oncology, and he is a Fellow of the American Association for the Advancement of Science.
Dr. Look received his MD degree and postgraduate training in Pediatrics from the University of Michigan, and his fellowship training in Pediatric Oncology at St. Jude Children’s Research Hospital. Prior to his appointment at Harvard, he was a professor at the University of Tennessee College of Medicine.
Dr. Stephen Skapek
Stephen Skapek, MD holds the Distinguished Chair in Pediatric Oncology Research at the University of Texas Southwestern Medical Center, where he serves as the Chief of the Division of Hematology-Oncology in the Department of Pediatrics, and the Medical Director the Pauline Allen Gill Center for Cancer and Blood Disorders at Children’s Medical Center in Dallas.
Dr. Skapek graduated from the Duke University School of Medicine, completed his pediatric residency training at the Wilford Hall Medical Center at Lackland AFB in San Antonio, Texas, and completed fellowship training in pediatric hematology and oncology at the Harvard Medical School’s Dana Farber Cancer Institute and Boston Children’s Hospital.
After completing his training, Dr. Skapek has focused clinical work on caring for children with rhabdomyosarcoma and other soft tissue sarcomas, and he has carried out both laboratory-based research in cancer and developmental biology and clinical research through the Children’s Oncology Group, which he serves as a member of the Scientific Council and Executive Committee and also as vice-Chair of the Soft Tissue Sarcoma Committee.
Dr. Lewis Silverman
Dr. Silverman is Director of the Pediatric Hematologic Malignancy Program at Dana-Farber Cancer Institute and Boston Children’s Hospital and is a Professor of Pediatrics at Harvard Medical School. He leads the DFCI ALL Consortium, a multi-institutional clinical trials group focused on developing more effective and less toxic therapies for children and adolescents with newly diagnosed ALL. He is the Principal Investigator of an international Phase III trial in pediatric Philadelphia chromosome-positive ALL being conducted by the Children’s Oncology Group (COG) and the multi-national European EsPhALL group. Other leadership roles include serving on the COG Scientific Council and as Scientific Chair for the TACL Consortium, which conducts trial for children with relapsed and refractory leukemia and lymphoma.
Dr. Sonali Barwe – A.I. duPont Hospital, Wilmington, DE
Children with acute myeloid leukemia (AML) having certain tumor proteins do not respond well to chemotherapy. These tumor proteins alter the way in which DNA is packaged in chromosomes and thereby turn on some tumor promoting genes while some tumor suppressing genes may be turned off. Fortunately, these marks can be easily removed and gene expression can be restored using specific drugs with lesser side effects than chemotherapy. We have generated mouse models using leukemic cells from such patients. These models faithfully replicate the human disease. We showed that combining two drugs which reverse these changes can completely cure mice transplanted with leukemic cells. The first goal of this proposal is to expand the study to test the efficacy of the drug combination to include more models. The second goal is to understand how these drugs work together to cure leukemia by using tools to detect the special marks and gene expression. The results obtained from this study will lay the foundation to allow the use of this drug combination in the clinic to treat children with AML.
Dr. Oren Becher – Lurie Hospital, Chicago, IL
Diffuse intrinsic pontine glioma, or DIPG, is an incurable brain cancer that mostly strikes young children. The median survival rate is less than one year after diagnosis. To date, there are no chemotherapeutic or targeted agents that have proven to be beneficial for treatment of these cancers. Dr. Becher leads one of very few laboratories around the world that focus exclusively on this type of deadly brain cancer. He is using a novel DIPG mouse model to study the function of proteins that drive tumor growth and to determine how novel anti-cancer drugs can inhibit tumor growth. His goal is to identify the most effective drugs against this type of brain cancer and then translate these findings by testing the drugs in clinical trials for children afflicted with this type of brain cancer. In this application, Dr. Becher is proposing to evaluate the anti-cancer activity of two novel cancer drugs alone and in combination in the newly developed improved DIPG mouse models.
Dr. Eleanor Chen – University of Washington, Seattle, WA
Rhabdomyosarcoma (RMS) is a devastating pediatric sarcoma. There is still no effective treatment for children with relapsed or wide-spread disease. In contrast to adult cancers, RMS has fewer DNA mutations, suggesting that other molecular changes may be driving tumor growth and progression. We have identified 40 potential candidate genes that function to alter DNA structure and packaging in the cells without causing DNA mutations. Previous data suggest that these genes may play a role in RMS. Some of these genes may work together to exert biological effects. My proposed research will apply genome engineering technology to target each individual candidate gene and gene combinations in RMS cells to identify the ones that are essential for RMS tumor growth. New targets identified from the study will be the basis for novel therapy designs to improve survival of RMS patients with advanced disease.
Dr. Xingguo Li – University of Rochester, Rochester, NY
Neuroblastoma is a common and deadly childhood cancer with an overall 5-year survival of less than 50% for high-risk tumors. Tumor initiating cells may drive therapeutic resistance and relapse which accounts for the majority of deaths in neuroblastoma. We have recently discovered a novel regulatory pathway involved in the cancerous properties of neuroblastoma tumor initiating cells. Our preliminary studies have further confirmed the therapeutic potential of using drugs to inhibit this pathway’s role in neuroblastoma cancer cells. In this project, we will determine the role of this pathway in the development of neuroblastoma and devise an approach to inhibit its cancerous activity with the long-term goal of improving neuroblastoma treatments for children diagnosed with this terrible disease.
Dr. Reshmi Parameswaran, Case Western Reserve, Cleveland, OH
Natural Killer (NK) cells are immune cells in our body which can kill cancer cells. Cancer cells often escape from NK cells mostly due to insufficient number and low activity of NK cells in cancer patients. Transforming Growth Factor beta is a protein produced by cancer cells which make NK cells less active. We will study the role played by this protein in suppressing NK cell activity in pediatric Acute Myeloid Leukemia patients. We will also use methods to neutralize Transforming Growth Factor beta to enhance NK cell activity and thus develop better treatment for pediatric Acute Myeloid Leukemia.
Dr. Ronald Parchem – Baylor College of Medicine, Houston, TX
One of the reasons that curing cancer is so difficult is that tumors are made up of many different types of cells, each with its own behavior and drug susceptibility. Researchers are beginning to appreciate that a small population of tumor cells, called cancer stem cells, are more aggressive and able to survive chemotherapy. Our goal is to understand how cancer stem cells acquire the properties that enable them to persist and metastasize, and to discover new ways to treat cancer by targeting them. In addition to improving treatment efficacy, therapies that target specific molecular pathways are better tolerated by patients. We previously showed that neural progenitors – stem cells that give rise to the nervous system during development – depend on the function of a gene, called microRNA-302 (miR-302); without miR-302, the nervous system does not form properly resulting in death. Our preliminary work in a brain cancer model of glioma shows that miR-302, ordinarily non-active after birth, is turned on in glioma, the most common type of brain cancer. Because miR-302 is active in stem cells, we hypothesize that miR-302 marks the cancer stem cell population in glioma and other related cancers. In this project, we will use multiple cancer models and experimental techniques to test the function of miR-302 in cancer stem cells, specifically on the aggressiveness of brain-related cancers, and will dissect the molecular pathways that control cellular behavior.
Dr. Kristopher Sarosiek – John B. Little Center for Radiation Sciences, Harvard Chan School
Central nervous system (CNS) tumors comprise a diverse group of cancer types and are a leading cause of cancer-related death in children. In addition to surgery, radiation and chemotherapy are the mainstays of treatment and although tumors frequently respond initially, tumor recurrence and treatment resistance is common. Importantly, radiation and chemotherapy treatments also damage healthy developing tissues in children and can cause life-long and devastating toxicities. When effective, most anti-cancer therapies induce apoptosis (programmed cell death) in cancer cells. However, CNS tumors frequently increase their expression of key pro-survival proteins from the BCL-2 family (BCL-2, BCL-XL and MCL-1) to block this form of cell death and support the development of resistance. The recent development of novel medicines that block pro-survival protein function has created an unprecedented opportunity to enhance the chemosensitivity of cancer cells and have already been approved for use in other malignancies. We propose to use cutting-edge tools to measure dependence on pro-survival proteins within pediatric CNS cancer cells in order to determine which cancers are most sensitive to these new therapies. In addition, we will comprehensively define the most effective strategies for combining these new medicines with existing treatments to inhibit the development of therapy resistance and improve cure rates while also reducing toxicities.
Dr. Bjoern Schwer – University of California, San Francisco, CA
Medulloblastoma is a brain tumor that primarily affects children and is the leading cause of cancer-related deaths in children. Currently, 30-40% of children with medulloblastoma die and therapies for treating medulloblastoma have not majorly changed since the 1980s. Recent research has shown that medulloblastoma actually represents many different types of tumors and potential factors driving medulloblastoma development have been proposed. However, these insights have not translated into improved patient outcomes because an efficient approach for validating these findings and for testing new therapies is lacking. We propose to address this critical need by developing an approach that will dramatically accelerate the identification of drivers of medulloblastoma and the testing of new therapies.
Dr. Leo Wang – City of Hope, Duarte, CA
Chimeric Antigen Receptor (CAR) T cells, recently approved by the FDA, have revolutionized leukemia treatment. However, CAR T cell solid tumor therapy has been disappointing, because myriad inputs contribute to make solid tumors resistant to immune attack. Indeed, despite our very encouraging initial clinical results using IL13Ra2-targeted CAR T cells in glioblastoma multiforme, benefit is only temporary; CAR T cells vanish from patients within 7 days of administration, and rapidly lose the ability to kill brain tumor cells in culture. Improving CAR T cell persistence will vastly improve their efficacy in treating brain tumors.
Doing this requires us to understand and manipulate protein-level events in CAR T cells, as proteins are the ultimate effectors of cellular function. Identifying proteins responsible for T cell persistence will be critical to keeping CAR T cells from disappearing. The best way to do that is with protein-focused techniques like mass spectrometry and mass cytometry.
I pioneered a groundbreaking technique for using mass spectrometry on small numbers of cells, which has not been possible before. We will use this and other protein-focused techniques, as well as biological models of brain tumors and the immune system, to identify a unique protein signature corresponding to T cell survival and persistence. We hypothesize that these activated protein circuits can be leveraged to improve CAR T cell persistence and efficacy.
Dr. Jason Yustein – Baylor College of Medicine, Houston, TX
Metastatic disease, which is when the cancer has spread throughout the body, is responsible for about 90% of all cancer related deaths. For children afflicted with metastatic osteosarcoma, the most common bone tumor in the pediatric population, it often means a very aggressive cancer that is associated with an extremely poor outcome. Unfortunately one reason for this unacceptable outcome is due our lack of understanding the biology of the metastatic state and identifying better treatment options.
Recently our laboratory has created a new mouse model of metastatic osteosarcoma (OS) that mimics the human tumor development and progression. Using the tumors from this model, we have been able to analyze genes and determine pathways that are functioning abnormally, including the identification of key alterations within metastatic tumors in a key pathway in the cell known as the Wnt cascade.
Our proposal will continue to investigate the exact role of Wnt signaling during metastatic development, or evolution, through both innovative pre-clinical models as well as functional and therapeutic studies. Furthermore, using these models we will test a new therapeutic agent designed to target this pathway that one day can be brought to the clinical care of these patients. Therefore, by gaining a better understanding of the detailed role of Wnt signaling during metastatic development, we will elucidate novel molecular aberrations and further identification of novel therapies.