Research: Current Research
Title: Discovery of novel environmental chemicals in a diverse population of maternal-infant pairs
In utero exposure to multiple environmental chemicals has been shown to adversely impact health throughout the lifespan, leading to adverse birth outcomes, neurodevelopmental deficits, diabetes and obesity, and cancer. Yet, a key data gap limiting our ability to characterize and address developmental health risks is the lack of data on the extent to which neonates are exposed to the vast array of industrial chemicals used in the US. Over 90% of the chemicals manufactured and used in high volumes (>25,000 pounds/year) in the US are not measured in large-scale human biomonitoring studies. Further, the current biomonitoring approach requires a priori selection of compounds for which to develop and validate targeted analytical methods; the lack of data on chemical use in industrial or commercial products hinders the ability to accurately anticipate to which of the almost 8000 high use chemicals the US population is most likely exposed. To address these challenges, our project will advance an innovative, discovery-driven research project using liquid chromatography-quadrupole time-of-flight mass spectrometry (LC-QTOF/MS) to perform a General Suspects Screen for the presence and co-occurrence of approximately 700 Environmental Organic Acids (EOAs) in a demographically diverse population of maternal-neonate pairs.
Status: Active, recruitment pending
Collaborators: Rachel Morello-Frosch (UC Berkeley), June-Soo Park (California Department of Toxic Substances Control), Tracey Woodruff (UCSF)
Funder: The National Institute of Environmental Health Sciences (NIEHS)
Title: A Non-targeted method for measuring multiple chemical exposures among a demographically diverse population of pregnant women in Northern California
This project involves an innovative non-targeted biomonitoring method using liquid chromatography-quadrupole time-of-flight mass spectrometry (LC-QTOF/MS) to evaluate everyday exposure to over 700 chemicals classified as Environmental Organic Acids (EOAs) and the extent to which exposures vary among different racial/ethnic and socio-economic groups of pregnant women. Our new LC-QTOF/MS non-targeted screening methodology has the capacity to directly (without enzymatic hydrolysis) and simultaneously screen for approximately 10-times more EOAs than what is currently being biomonitored in the National Health and Nutrition Examination Survey.
We focus on EOAs, which are industrial compounds with at least one ionizable proton, because: 1) their chemical structure facilitates a higher rate of analytical detection; 2) many of their chemical structures are similar to hormones, increasing the potential for endocrine disruption, which can negatively affect fetal development; and 3) many are produced in high quantities and used in a wide range of consumer products, but have not been extensively biomonitored in pregnant women. We will use liquid chromatography tandem mass spectrometry (LC-MS/MS) to confirm the presence and levels of select EOAs identified through our non-targeted screening. Finally, we will assess differences in EOA exposures by race/ethnicity and socio-economic status.
We hypothesize that pregnant women are exposed to more EOAs than previously documented, and that EOA exposure varies by race/ethnicity and SES, resulting in disproportionate EOA body-burdens among certain subpopulations.
Status: Active, recruiting
Collaborators: Rachel Morello-Frosch (UC Berkeley), Roy Gerona (UCSF), Tracey Woodruff (UCSF)
Funder: US Environmental Protection Agency
Title: Chemicals in Our Drinking Water; General suspects screening of environmental chemicals in Northern and Central California pregnant women and drinking water.
In the Chemicals in our Drinking Water Study, we will use liquid chromatography-quadrupole time-of-flight mass spectrometry (LC-QTOF/MS) to perform a general suspect screen for the presence and co-occurrence of ~700 Environmental Organic Acids (EOAs) in the serum and residential drinking water of pregnant women. We define EOAs to be organic industrial chemicals that have at least one dissociable proton. EOAs include phenolic compounds and carboxylic, phosphonic and sulfonic acids, such as: environmental phenols (e.g. Bisphenol A (BPA)); phthalate metabolites; phenolic metabolites of polybrominated diphenyl ethers (OH-PBDEs) and polychlorinated biphenyls (OH-PCBs); perfluorinated compounds (PFCs); and phenolic and acidic pesticides and/or their predicted acidic and phenolic metabolites. Many EOAs that are not currently biomonitored are structurally similar to chemicals that have been shown to adversely impact development (e.g. bisphenol A), often due to their ability to disrupt the endocrine system.
We will perform a general suspects screen of environmental organic acid chemicals (EOAs) in biospecimens and drinking water samples to evaluate (1) potential EOA exposures among pregnant women; and (2) drinking water as a source of exposure to multiple EOAs.
Status: Active, recruiting
Collaborators: Lauren Zeise (CalEPA OEHHA), Roy Gerona (UCSF), June-Soo Park (California Department of Toxic Substances Control), Tracey Woodruff (UCSF)
Funder: California Environmental Protection Agency’s Office of Environmental Health Hazard Assessment (CalEPA OEHHA)
Title: A Program of Research in Population Cytogenetics
Despite the importance of maternal meiotic errors to the etiology of human chromosome abnormalities, we know very little about chromosome dynamics during human female meiosis, and remain ignorant of the reasons why the process is so error-prone. In the studies that comprise this project, we will directly examine meiosis in human oocytes, and combine this approach with molecular and quantitative methodologies to address these deficiencies.
Specific Aim 1: To examine synapsis and recombination in human oocytes, asking how these processes are linked to one another and how variation in DNA sequence affects them.
a) How does meiotic synapsis occur in fetal oocytes and are sites of synaptic initiation “translated” into sites of crossing-over?
b) Does variation in DNA sequence cause variation in the number of cross-overs?
Specific Aim 2: To examine the contribution of fetal female meiotic abnormalities to human nondisjunction, testing specific hypotheses of the genesis of maternal age-dependent trisomies.
Status: Active, recruiting
Collaborators: Terry Hassold and Pat Hunt (Washington State University), Vic Fujimoto, Roy Gerona, and Tracey Woodruff (UCSF)
Funders: The National Institute of Environmental Health Sciences (NIEHS), The National Institute of Child Health and Human Development (NICHD), Washington State University
Learn more about PRHE's research approach here.