Center for Integrative Research on Childhood Leukemia and the Environment (CIRCLE)
Center Location: Berkeley, CA
Public Health Impacts: Researchers in the Center for Integrative Research on Childhood Leukemia and the Environment (CIRCLE) are studying whether chemical exposures in the womb may increase the risk of childhood leukemia, and what changes at the cellular level may lead to the disease. Results from these studies may inform steps that families and health care providers can take to prevent childhood leukemia.
Primary Environmental Exposures: In utero chemical exposures (e.g., pesticides, paints, and solvents)
Primary Health Outcomes: Childhood leukemia
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Principal Investigator: Catherine Metayer, M.D., Ph.D.
Pediatric Health Specialist: Gary Dahl, M.D.
Specialties: Pediatric hematology and oncology
Project 2 Leader: Stephen M. Rappaport, Ph.D.
Project 3 Leader: Joseph L. Wiemels, Ph.D.
Community Outreach & Translation Core Leader: Mark Miller, M.D.
Mouse Model Service Core Leader: Scott Kogan, M.D.
Faculty Development Investigator: Todd Whitehead, Ph.D.
Center Description & Activities
Researchers in CIRCLE work to identify the causes of childhood acute lymphoblastic leukemia (ALL) with the goal of prevention. During the last 50 years, the incidence of ALL has steadily increased in children, with the highest rates seen in Latinos. Center researchers use state-of-the-art methods to identify additional chemicals that increase ALL risk and to characterize the biological mechanisms by which exposures to such chemicals increase leukemia risk.
CIRCLE researchers are integrating ethnically diverse population-based studies with basic research, including use of a mouse model of childhood ALL. They conduct epidemiological and laboratory analyses in order to understand how certain chemicals increase the risk of childhood ALL via immunological, genetic and epigenetic mechanisms. CIRCLE researchers use unique resources from the California Childhood Leukemia Study (1,000 childhood ALL cases and 1,000 controls) and the California Mother-Child Birth Cohort (600 mother-child pairs), including blood samples from children and their mothers that are archived at the California Department of Public Health. The study also has access to detailed chemical exposure data and information on factors that may influence a child's immune status.
Project 1: In Utero Chemical Exposures, Immune Status, and Childhood Leukemia
Some chemicals associated with an increased risk of childhood ALL have been shown to affect the immune system. To learn more about this relationship, researchers investigate how in utero chemical exposures affect the neonatal and maternal immune system. This project uses archived samples, including neonatal blood spots and blood samples from pregnant women, to measure maternal and neonatal immune status.
Project 2: Identifying in Utero Exposures That Are Risk Factors for Childhood Leukemia
Project Leader: Stephen M. Rappaport, Ph.D.
Researchers are conducting an exposome-wide association study to characterize all chemical exposures in maternal and neonatal biological samples in order to identify previously unknown in utero risk factors for childhood ALL. Researchers also perform targeted analyses of biomarkers that indicate exposure to factors that have been previously associated with childhood ALL. This project seeks to determine whether specific in utero chemical exposures, as measured by constituents of the fetal-blood exposome, affect developmental programming in ways that increases the risk of childhood ALL.
Project 3: Prenatal Exposures, Constitutive Genetics, DNA Methylation, and Childhood Leukemia
Project Leader: Joseph L. Wiemels, Ph.D.
Project 3 researchers are working to better understand how prenatal exposures affect DNA methylation. Epigenetic changes such as DNA methylation are chemical modifications that affect gene expression without changing a person’s underlying genetic code. The researchers are using animal studies and findings from projects 1 and 2 to evaluate how chemical, immune, and dietary factors can perturb DNA methylation and, in turn, affect childhood ALL risk.
Community Outreach & Translation Core
Core Leader: Mark Miller, M.D.
The Community Outreach and Translation Core (COTC) transmits CIRCLE research findings to health-care professionals, families, patient advocacy groups, and policy and public health authorities, and provides a scientific basis for developing prevention programs for childhood leukemia. The COTC partners with Commonweal, a non-profit organization, and with the Western States Pediatric Environmental Health Specialty Unit to improve environmental health literacy via a variety of media, including training materials, a multimedia Story of Health E-book, and various symposia. The COTC places a special emphasis on reaching the Latino community and improving awareness of the role of pre-conception and prenatal exposures in initiating childhood leukemia.