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Funding Childhood Cancer Research

 

The Andrew McDonough B+ Foundation® is proud to announce the recipients of the Fall 2020  Research Grant Cycle. Please see below for a list of the awardees.

Seattle Children's Hospital Research Foundation

Part of our mission is to provide childhood cancer funding. We are 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 childhood cancer research funding.

 

Scientific Advisory Board

The members of The B+ Foundation Scientific Advisory Board are:

Dr. Peter C. Adamson

Peter C. Adamson, MD is Global Development Therapeutic Area Head, Oncology and Pediatric Innovation at Sanofi. Dr. Adamson leads global cancer drug development for Sanofi and is also working across therapeutic areas to further pediatric drug development efforts. Prior to this, Dr. Adamson served as Chair of the Children’s Oncology Group (COG), a National Cancer Institute supported international consortium of more than 220 childhood centers. Dr. Adamson, currently Emeritus Professor of Pediatrics and Pharmacology at the Perelman School of Medicine, is Board Certified in Pediatric Hematology/Oncology and Clinical Pharmacology. He was appointed by President Obama to, and continues to serve on, the National Cancer Advisory Board (NCAB), and also served on the Blue-Ribbon Panel for the Beau Biden National Cancer Moonshot Initiative.

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. Douglas Hawkins

Douglas S. Hawkins, MD, is the Group Chair of the Children’s Oncology Group (COG). COG is the world’s largest organization devoted exclusively to childhood and adolescent cancer research. COG unites over 10,000 experts in childhood cancer at more than 200 leading children’s hospitals, universities, and cancer centers across North America, Australia, and New Zealand in the fight against childhood cancer. Dr. Hawkins is also a clinician at Seattle Children’s Hospital and Professor of Pediatrics at the University of Washington School of Medicine.

Prior to becoming COG Group Chair in 2020, Dr. Hawkins was the Chair of the COG Soft Tissue Sarcoma Committee, overseeing the conduct of biology studies and clinical trials for rhabdomyosarcoma and other soft tissue sarcomas across North America. He was a member of the COG Bone Tumor Steering Committee. Dr. Hawkins had focused on clinical research, particularly in the treatment of pediatric sarcomas. He was the chair of two COG clinical trials, one for Ewing sarcoma and another for rhabdomyosarcoma. He chairs the international EURO EWING Consortium External Advisory Board and also chairs the international Frontline and Relapse in RhabdoMyoSarcoma Study (FaR-RMS) Data Monitoring Committee.

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. 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. 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. 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. 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. 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. Sarah K. Tasian

Sarah K. Tasian, MD is a pediatric oncologist and physician-scientist at the Children’s Hospital of Philadelphia and University of Pennsylvania School of Medicine who is interested in development of molecularly-targeted therapeutics for children with high-risk leukemias. She is a graduate of the University of Notre Dame (BS, BA) and Baylor College of Medicine (MD), and she trained in Pediatrics at Seattle Children’s Hospital and in Pediatric Hematology-Oncology at University of California, San Francisco (UCSF). She specialises in the clinical care of children with hematologic malignancies and is an internationally-recognized expert in pediatric ALL and AML. Her bench-to-bedside and bedside-back-to-bench translational laboratory research program focuses upon testing of kinase inhibitors and chimeric antigen receptor (CAR) T cell immunotherapies in genetic subsets of childhood ALL and AML. Dr Tasian has leadership roles in the Children’s Oncology Group (COG) ALL and Myeloid Diseases committees and Leukemia Lymphoma Society PedAL/EUpAL consortium, is the COG Developmental Therapeutics committee Vice-Chair of Biology for Hematologic Malignancies, and leads or co-leads several national or international early phase clinical trials testing precision medicine therapies in children with high-risk leukemias.

Investigators interested in applying for a research grant from The Andrew McDonough B+ Foundation can find more information here.

Recent B+ Grants Awarded to:

Dr. Ranjit Bindra – Yale University, New Haven, CT

Exploiting NAD Metabolism Defects in Pediatric Brain Tumors

Better therapies are needed for pediatric brain tumors, especially those which target the underlying mutations associated with these cancers. We discovered that mutations in a gene, PPM1D, which are commonly seen across multiple unique types of pediatric brain tumors, induce profound defects in cellular metabolism. These defects induce exquisite sensitivity to a class of drugs which target this metabolic pathway, which have been tested before in clinical trials for other tumors. Here, we seek to develop a novel regimen using these drugs against pediatric brain tumors with PPM1D mutations. We will test our approach using pediatric brain tumor models in vitro and in vivo. The work proposed in this application will form the basis for advancing these drugs into clinical trials, and thus has the potential to uncover new therapeutics for children with brain tumors.

Dr. Sofia de Oliveira – Albert Einstein College of Medicine, New York, NY

The role of inflammation in the liver microenvironment of a Fibrolamellar Carcinoma zebrafish model

Fibrolamellar Carcinoma (FLC) is a rare type of liver cancer that mainly affects children and young adults. The only genetic anomaly that has been associated with FLC is the DNAJB1-PRKACA fusion transcript (DnaJ-PKAc). Recently we have developed a FLC zebrafish model and reported that DnaJ-PKAc expression in hepatocytes triggers inflammation and induces inflammasome activation. There is a growing interest in potential contributions of innate immune cells on modulating tumorigenesis, which is leading to innovative strategies with the goal to elicit a more integrated immune response against cancer. Therefore, it is crucial to understand the role of innate immune cells in the liver microenvironment, and how they can modulate liver immune landscape. The zebrafish is the smallest and only vertebrate system that allows the visualization of the liver using non-invasive live imaging techniques, which makes our zebrafish FLC model an essential tool for studying the pathobiology of this malignancy. Here we propose to use our model to investigate how innate immune cells modulate liver microenvironment and immune landscape via inflammasome-mediated instruction in FLC. Our work will unravel immune mechanism involved on FLC biology, with the goal of developing effective immune therapies targeting FLC. In addition, our novel approach will expand our understanding about how innate immune cells are involved in the crosstalk and further instruction of adaptive immunity in the liver.

Dr. Anthony Faber – Virginia Commonwealth University, Richmond, VA

MYCN-amplified neuroblastoma are addicted to iron and vulnerable to system Xc- inhibition

Neuroblastoma with extra amounts of a protein called MYCN is a particularly deadly childhood cancer. MYCN is responsible for the poor outcomes, however, new therapies to target MYCN positive (called MYCN-amplified) neuroblastoma have been elusive. Iron is used by cancer cells to support its abnormal growth demands. A new form of iron-dependent cell death, called ferroptosis, has recently been identified. Here in this grant, we have uncovered that MYCN-amplified neuroblastoma are vulnerable to ferroptosis because they trap iron into the cell. We have found this can be used against MYCN-amplified neuroblastoma by treating cells with drugs that take advantage of the increased iron and induce ferroptotic cell death. In particular, we identify two drugs that are FDA-approved for other indications, and can be “repurposed” to treat MYCN-amplified neuroblastoma. We will further test these two drugs (sulfasalazine and auranofin) to determine whether they can shrink tumors in sophisticated models of MYCN-amplified neuroblastoma. The goal of which is to prepare these treatments for clinical trials.

Dr. Alex Huang – Case Western Reserve University School of Medicine, Cleveland, OH

First-in-class oral inhibitor of TGF-beta receptor in humanized mouse model of advanced osteosarcoma

Osteosarcoma (OS) is the most prevalent malignant bone cancer with a high propensity for lung metastasis in children and adolescent and young adults (AYA), with ~400-600 cases a year in the United States. Despite aggressive chemotherapy and surgery, the outcome for pulmonary metastatic OS (pOS) and recurrent/refractory OS (rOS) remains poor over the past 4 decades. Transforming growth factor-? (TGF-ß) is one of the most abundant cytokines in OS tumor microenvironment (TME), and correlates with high grade OS and lung metastases. Therefore, effectively targeting TGF-ß would be a desirable treatment approach. TEW-7197 (“Vactosertib”) is a first-in-class, non-toxic, orally available small molecule inhibitor of the TGF-ß type I Receptor (TßRI) kinase currently in adult Phase I clinical trial. Our preliminary data show that blocking TGF-ß signaling with oral TEW-7197 significantly reduced advanced late-stage preclinical OS models in vivo. We hypothesize that TEW-7197 will be an effective therapy against pOS and rOS by modifying tumor-intrinsic and extrinsic immune-related pathways to achieve clinical efficacy, and we will validate this hypothesis by validating TEW-7197 effect using a unique humanized mouse model consists of fully reconstituted human immune system. This research will establish a critical role of TGF-ß signaling in pOS progression and provide scientific rationale to develop a clinical trial targeting TGF-ß signaling with Vactosertib.

Dr. Christopher Klebanoff – Memorial Sloan Kettering Cancer Center (MSK), New York, NY

T cell immunotherapy targeting fusion-derived “public” neoantigens expressed by pediatric desmoplastic small round cell tumors

A subset of cancer mutations, termed neoantigens (NeoAgs), activate T white blood cells. NeoAg-specific T cells can induce cancer regression without injuring healthy tissues when used as an immunotherapy. Many pediatric cancers are caused by a distinct type of mutation in which one gene is fused to another (driver fusions). Driver fusions might represent a particularly immune-stimulating subset of NeoAgs because they create chimeric, or “monster”, proteins that appear foreign to a patient’s immune system. Desmoplastic small round cell tumor (DSRCT) is a rare and highly fatal pediatric sarcoma characterized by a fusion between the EWSR1 and WT1 genes. We hypothesize that the EWSR1-WT1 fusion protein creates shared, or “public”, NeoAgs that can be targeted using off-the-shelf cellular immunotherapies. To test this hypothesis, we have assembled a multidisciplinary team comprised of experts in cellular immunotherapy and pediatric oncology. In Aim 1 of our study, we will perform a mass spectrometry screen to identify and characterize NeoAgs resulting from the EWSR1-WT1 fusion protein that are compatible with prevalent tissue types. In Aim 2, we will use a novel T cell receptor (TCR) discovery and gene-sequence retrieval platform to create a library of therapeutic immune receptors specific for “public” EWSR1-WT1 NeoAgs. Success of this research will establish the framework for an innovative new class of cellular immunotherapies with curative potential for patients with DSRCT.

 

Click below on examples of grants that we have provided

Click on any title for more information about that grant, or more grants here.

Targeting Signaling Pathways in Pediatric AML

Baylor College of Medicine, Houston, TX

Reversing NK Cell Dysfunction in Pediatric Cancer

Case Western Reserve, Cleveland, OH

BioStatistician

Children’s Oncology Group, Monrovia, CA

Project EveryChild

Children’s Oncology Group, Philadelphia, PA

Zebrafish Models of Human AML

Dana-Farber/Harvard Medical Center, Boston, MA

Contribution of RNA Binding Proteins to Neuroblastoma Aggression

Emory University – Winship Cancer Institue, Atlanta, GA

ACVR1 as a Treatment to Pediatric Cancer

Georgia Tech Research Corporation, Atlanta, GA

Defining Actionable Apoptotic Dependencies in Pediatric CNS Tumors

John B. Little Center for Radiation Sciences, Harvard Chan School, Boston MA

Activation of NF-k8 in Neuroblastoma Myeloid Cells

Johns Hopkins University School of Medicine, Baltimore, MD

Targeting MEK and CDK4/6 in DIPG

Lurie Hospital, Chicago, IL

Polycomb inhibition sensitizes AML to anthracycline therapy

The Research Institute at Nationwide Children’s Hospital, Columbus, OH

Phase II Ewing’s Sarcoma Clinical Trial

Nemours/A.I. DuPont Hospital, Wilmington, DE

Epigenetic Therapy in AML

Nemours/A.I. DuPont Hospital, Wilmington, DE

L3MBTL3, A Therapeutic Target in AML

The Regents of the University of Michigan, Ann Arbor, MI

Tumorigenesis of Pediatric Liver Cancer

The Rockefeller University, New York, NY

 

Immunotherapy

Seattle Children’s Hospital, Seattle, WA

Single-Cell Proteomic to Relapse in Pediatric AML

Stanford University, Stanford, CA

Artificial Intelligence for Pediatric Cancer Imaging

Stanford University, Stanford, CA

Pediatric Cancer Genome Project

St. Jude Children’s Research Hospital, Memphis, TN

Understanding the role of SMARCD1 in malignant rhabdoid tumors

Trustees of Dartmouth College, Lebanon, NH

Pediatric Cancer Data Commons

University of Chicago, Chicago, Illinois

Overcoming Innate Immune Evasion in Pediatric High-Grade Glioma

University of Colorado Denver, AMC and DC, Aurora, CO

Disrupting Neuroblastoma Tumor-Initiating Cells

University of Rochester, Rochester, NY

Targeting RNA Processing Defects of Ewing Sarcoma

UT Health Science Center at San Antonio, San Antonio, TX

New Therapeutic Targets for Rhabdomyosarcoma

UT Southwestern Medical Center, Dallas, TX

Developing a Novel Therapeutic Strategy for Rhabdomyosarcoma

UT Southwestern Medical Center, Dallas TX