Our work has focused on molecular epidemiology and monitoring of environmental exposures and effects associated with human health using a broad spectrum of biomarkers. Our scientific interests include functional genomics, epigenetics, reproductive toxicology and biobanking. Most of the projects in my Laboratory of Children’s Environmental Health are unified by the theme of biomarkers in children and fetal origins of human health. Currently, the main focus of research is on development and implementation of the genetic and epigenetic biomarkers in children studies, and on molecular mechanisms of obesity and neurotoxicity.
Environmental Epigenetics and Children’s Health
CHAMACOS: The Center of Health Assessment of Mothers and Children of Salinas (CHAMACOS) is a longitudinal prospective cohort study through CERCH at UC Berkeley. CHAMACOS aims to study the effects of pesticides on the health of mothers and their children in the Salinas Valley of California.
The field of epigenetics is especially relevant to environmental epidemiologists because it is a biological mechanism linking early life environmental exposures to later life health outcomes. Epigenetic markers include DNA methylation, non-coding RNAs like miRNAs, and chromatin modifications. We have conducted epigenetic research in the CHAMACOS cohort since 2009. We have published on the effects of age, sex, blood cell composition, puberty, prenatal exposures to phthalates, smoking and other environmental chemicals. The Holland lab receives biological samples, including blood and urine, from CHAMACOS study participants. At the Holland lab the blood is processed, labeled, entered into our database, and stored safely in our biorepository for future analysis. Click here for CHAMACOS publications CHAMACOS Blood Processing Mini-Tutorial |
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PACE: We are also active participants in the Pregnancy and Child Epigenetics (PACE) consortium, an NIEHS coordinated effort to study effects of smoking and other factors on DNA methylation by 450K and 850K in newborn and child blood in more than 20 birth cohorts. Thus far, we have published meta-analyses of relationships between cord blood DNA methylation and maternal BMI, smoking, and birthweight among others.
PON1 Functional Genomics
PON1 has been a special focus of our research for the last 12 years, with more recent expansion in the novel area of epigenetics of paraoxonase as a candidate gene. The PON1 gene encodes for the paraoxonase, a protective enzyme which is involved in oxidative stress pathways and can detoxify some metabolites of organosphosphate pesticides. In the CHAMACOS birth cohort, we found a more than 100-fold range of levels and substrate-specific PON1 activities, due in part to age and genotype. We have showed that young children, especially newborns, have much lower levels of this protective enzyme than their mothers and are therefore more vulnerable to pesticide exposures than adults. We also found several genotypes were associated with higher levels and/or substrate-specific activities of PON1. More recently, we have expanded our PON1 functional studies to epigenetics. We have shown that PON1 DNA methylation mediates the association of PON1 promoter genotypes with PON1 protein levels in children and have reported suggestive associations of PON1 DNA methylation and neurobehavior.
Biomarkers in Environmental Studies
Over the years we have studied a broad range of biomarkers of exposure and effect in populations of children and young adults, ranging from molecular cytogenetics, immunological markers, microbiome and biomarkers of oxidative stress and obesity.
CHAPS: Children's Health and Air Pollution Study
COEH: Center for Occupational and Environmental Health
CHAPS: Children's Health and Air Pollution Study
COEH: Center for Occupational and Environmental Health
