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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-