Grants and Fellowships | 2014

56 Post-Doctoral Fellowships Metabolomics and Adductomics Analysis of Dried Blood Spots (DBS) from the Northern California Childhood Leukemia Study (NCCLS) Since 2001 researchers have mainly examined the human genome (G) to discover causes of disease despite evidence that G explains only 10-15% of the chronic-disease risks. Therefore, it is probable that most of these risks arise from the exposome (E, representing all exposures) and from G×E interactions. Since both endogenous and exogenous exposures express themselves chemically, blood specimens can be used for conducting exposome-wide association studies (EWAS) in order to identify causal environmental exposures. An EWAS begins by comparing profiles of thousands of small molecules (metabolomics) and/or large molecules (proteomics) in serum or plasma from diseased and healthy subjects. Omic features that differ between populations are then identified and used as targeted biomarkers in follow-up studies to confirm causality, to identify exposure sources, and to investigate mechanisms of action. Leukemia makes up approximately 35% of all childhood cancers (ages 0-14), yet, its etiology is mostly unknown. Established risk factors (e.g. genetic conditions, ionizing radiation, and chemotherapeutic agents) account for only 10% of the causes, while suspected risk factors include chemical exposure, tobacco smoke, viral infection, dietary exposures, and non-ionizing radiation exposure of either the child and/or parent. Using the EWAS approach, a subset of dried blood spots (DBS) from the Northern California Childhood Leukemia study (1,000 cases and controls) will be analyzed using mass-spectrometry- based metabolomics and adductomics (a variant of proteomics that focuses on adducts of reactions between human serum albumin and reactive electrophiles) to identify and quantify discriminating features between cases and controls. Using elements of exposure biology, the molecular linkages between exposure and disease risk will be explored. As the DBS were obtained prior to the onset of disease during routine heal prick after birth, this matrix offers a unique snapshot of prenatal exposure. Fellow Lauren Petrick University of California, Berkeley, USA Supervisor Stephen Rappaport 2014-