Southern California Environmental Health Sciences Center

A cross-cutting thematic research framework

Scientifically, the SCEHSC is organized around six Environmental Health Research Programs. These include two Methods Research Programs (RP), Exposure Sciences and Biostatistics & Data Science, and four Health Outcomes RP, Cardiorespiratory; Neurological; Obesity & Metabolic; Cancer. These are integrated by a cross-cutting thematic research framework examining critical developmental periods, population vulnerability, and shared molecular and biological processes of disease. The Center is making a concerted effort to support new collaborations with existing cohorts that were not originally developed to study environmental risk factors. Cores, pilot projects, and administrative support have helped Center investigators pioneer environmental epidemiology in Kaiser Permanente Southern California (KPSC), the Adolescent Brain Cognitive Development (ABCD) study as ABCD-E[nvironment], the Multiethnic Cohort (MEC) study of cancer and in the Women’s Health Initiative Memory Study (WHIMS), in addition to cohorts the Center has helped create (such as the maternal and developmental risks from environmental and social stressors (MADRES) pregnancy and Children’s Health Study cohorts).

The Community Engagement Core (CEC) continues to help communities develop capacity, environmental literacy, and understanding of exposures to neighborhood level air pollution in Southern California environmental justice communities. The Core developed infographics about hexavalent chromium and ethylene oxide in response to local exposures and community concerns, since adapted to communities across the country. Publicly accessible materials on impacts of lead on vulnerable populations and measures to mitigate exposure have been developed for communities affected by the Exide secondary smelter that exposed tens of thousands of people to hazardous levels. Versions of a lead infographic have been developed in Korean, in addition to Spanish and English, reflecting the ethnically diverse exposed population. The Core has an increasingly active social media presence across multiple platforms reporting on research results from the Center and issues of concern to communities, including lead, oil drilling, and health effects of heat waves, the latter in partnership with the City of Los Angeles and local community-based organizations. Center research was important scientific evidence leading to the City of L.A. passing a bill to phase-out all urban oil drilling; the state subsequently passed legislation providing for a 3,200-foot buffer between oil and gas operations and sensitive receptors. Center members, including CEC staff, regularly respond to media requests, as described in the RPPR section about the CEC. In partnership with the USC Children’s Environmental Health Research Translation Center, a Be Heard! series of webinars has been developed to train junior investigators to partner with communities to provide testimony on environmental health science at request of local or state policy makers, to comment on EPA rulemaking requests, and on how to write commentaries and opinion pieces.

The career development program has several accomplishments to report from Center New Investigators. Dr. Aung successfully competed as the MPI (with Center Deputy Director, Lida Chatzi) for a new U01 award (1U01HG013288) in which multi-omic signatures, environmental exposures, and social and behavioral factors will be used to detect and assess molecular “profiles” characterizing the etiology and progression of non-alcoholic fatty liver disease (NAFLD) in Latino youth. This longitudinal investigation will integrate these data and clinical characteristics to identify precise risk profiles of NAFLD risk, and disease progression and severity. A Center pilot project supported New Investigator Erika Garcia in developing her interest in climate change and health, leading to important contributions to a new body of literature showing associations of co-occurring extreme heat and particulate matter on suicide and homicide;² and showing disparities in adaptation to wildfire smoke.³ She also found disparities in electric vehicle (EV) adoption and in real world impacts of EV adoption on air pollution and health.⁴ The latter led to Dr. Garcia’s successful competition for her first R01 (1R01ES035137) to assess air pollution exposure reductions and respiratory health benefits of EV adoption, and social disparities in adoption and corresponding benefits. A key aim of the study is to understand barriers to EV adoption in underserved communities in community engaged research developed in collaboration with CEC director Jill Johnston.

Several important papers were published from the neurological outcomes research program, spanning bench studies of effects of particulate matter on neuronyl and oligodendrocyte apoptosis in mice in a sex-specific effect on males,⁵ to studies of air pollution associations with emotional behavior and longitudinal development of brain networks in the Adolescent Brain Cognitive Development study.^6,7 Prenatal exposure to organophosphate esters with subsequent neurobehavioral outcomes was reported in children in the MADRES cohort.⁸ Novel exposure assessment methods identified prediction algorithms to explain liver polyfluoroalkyl substances (PFAS) accumulation based on plasma measurements⁹ and associations of prenatal aircraft-specific ultrafine particles with subsequent onset of autism in children.¹⁰ Distinct travel behavior effects were reported to increase exposure measurement error in individuals with high mobility.¹¹ Investigators in the biostatistics methods research program developed improved methods for assessing geneenvironment interactions.¹² Work in the CEC led to identifying important research questions that have been addressed in the context of community engaged research about effects of urban oil and gas production, and of the environmental injustice of exposures to hydrogen sulfide releases that are allowed to occur and continue in marginalized communities, RPPR Page 5 which were separately funded by NIEHS.^13,14 This research was conducted by postdoctoral fellows supported by the NIEHS-funded T32 on Environmental Genomics and by a pilot project from a cost share from the Keck School of Medicine, under supervision of Dr. Johnston.

The Center has prioritized new opportunities to show effects of environment on cancer, in collaboration with the USC Norris Cancer Center. The Center jointly sponsored an off-campus retreat with the Cancer Center attended by 70 investigators and including invited speakers Brahmar Mukerjee from University of Michigan and Catherine Metayer from UC Berkeley. The Center, together with the Cancer Center, will jointly fund at least one pilot project this year. Another major effort this year was a workshop on PFAS that led to a Superfund Research Program application, which is pending review. The Center has supported essentially all of these efforts, as indicted above and through the EFC, BFC or IHSFC. Research program investigators regularly advise the CEC on development of new infographics and research relevant to work with community groups or on testimony when requested by policy makers; community engagement periodically identifies an important research question that would not otherwise have occurred to Center investigators and can lead to Research to Action or CBPR applications, as described in examples above.

References

1. Lim SS, Vos T, Flaxman AD, et al. A comparative risk assessment of burden of disease and injury attributable to 67 risk factors and risk factor clusters in 21 regions, 1990-2010: a systematic analysis for the Global Burden of Disease Study 2010. Lancet (London, England) 2012;380:2224-60.

2. Rahman MM, Lorenzo M, Ban-Weiss G, et al. Ambient temperature and air pollution associations with suicide and homicide mortality in California: A statewide case-crossover study. Sci Total Environ 2023;874:162462.

3. Palinkas LA, De Leon J, Yu K, et al. Adaptation Resources and Responses to Wildfire Smoke and Other Forms of Air Pollution in Low-Income Urban Settings: A Mixed-Methods Study. Int J Environ Res Public Health 2023;20.

4. Garcia E, Johnston J, McConnell R, Palinkas L, Eckel SP. California's early transition to electric vehicles: Observed health and air quality co-benefits. Sci Total Environ 2023;867:161761.

5. Lamorie-Foote K, Liu Q, Shkirkova K, et al. Particulate matter exposure and chronic cerebral hypoperfusion promote oxidative stress and induce neuronal and oligodendrocyte apoptosis in male mice. J Neurosci Res 2023;101:384- 402.

6. Campbell CE, Cotter DL, Bottenhorn KL, et al. Air pollution and age-dependent changes in emotional behavior across early adolescence in the U.S. Environ Res 2024;240:117390.

7. Cotter DL, Campbell CE, Sukumaran K, et al. Effects of ambient fine particulates, nitrogen dioxide, and ozone on maturation of functional brain networks across early adolescence. Environ Int 2023;177:108001.

8. Hernandez-Castro I, Eckel SP, Howe CG, et al. Prenatal exposures to organophosphate ester metabolite mixtures and children's neurobehavioral outcomes in the MADRES pregnancy cohort. Environ Health 2023;22:66.

9. Baumert BO, Fischer FC, Nielsen F, et al. Paired Liver:Plasma PFAS Concentration Ratios from Adolescents in the Teen-LABS Study and Derivation of Empirical and Mass Balance Models to Predict and Explain Liver PFAS Accumulation. Environ Sci Technol 2023;57:14817-26.

10. Carter SA, Rahman MM, Lin JC, et al. Maternal exposure to aircraft emitted ultrafine particles during pregnancy and likelihood of ASD in children. Environ Int 2023;178:108061.

11. Yougeng Lu RH. Impacts of distinct travel behaviors on potential air pollution exposure measurement error. Atmospheric Environment 2023;306.

12. Kawaguchi ES, Kim AE, Lewinger JP, Gauderman WJ. Improved two-step testing of genome-wide geneenvironment interactions. Genet Epidemiol 2023;47:152-66.

13. Quist AJL, Johnston JE. Malodors as environmental injustice: health symptoms in the aftermath of a hydrogen sulfide emergency in Carson, California, USA. J Expo Sci Environ Epidemiol 2023.

14. Chan M, Shamasunder B, Johnston JE. Social and Environmental Stressors of Urban Oil and Gas Facilities in Los Angeles County, California, 2020. Am J Public Health 2023;113:1182-90.