Research | Huels Lab

SELECTED ON-GOING PROJECTS

Air Pollution and Dementia

A main research focus of our group is to better understand how air pollution impacts the human brain and cognitive functioning. This research is currently supported by three major NIH/NIA awards:

IMPACT-ADRD: Investigating the Multi-omics Perturbations Associated with Complex Environmental Toxicants and their Contribution to Alzheimer's Disease and Related Dementias (NIH/NIA U01AG088425; MPIs Huels/Liang/Wingo; contact PI: Huels)

By using innovative targeted and untargeted exposure assessment, single- and multi-omics analysis, and cross-tissue approaches, our primary objective is to offer valuable insights into how individual PM2.5 pollutants and mixtures interact with biological responses across epigenome, proteome, and metabolome, ultimately contributing to our understanding of AD/ADRD. This knowledge can aid future endeavors aimed at shaping environmental regulations and health policies to reduce the risk of AD/ADRD associated with air pollution.

Air pollution, the blood and brain metabolome and their effects on Alzheimer's disease and related dementias (NIH/NIA R01AG087250; MPIs Huels/Liang; contact PI: Huels)

Despite the observed epidemiological evidence, the detailed molecular mechanisms explaining how air pollution exposures (both individually and as a mixture) affect Alzheimer’s Disease and related dementias (AD/ADRD) are still largely unknown. We will investigate the molecular connections underlying the neurotoxicity of air pollution using innovative cross-tissue approaches, with the overarching goal of providing key insights into the relationship between air pollution mixtures, biological response profiles, and AD/ADRD, supporting future efforts that aim to inform environmental regulation and health policy to mitigate air pollution-related risk for AD/ADRD.

Air pollution and early signs of dementia (NIH/NIA R01AG079170; MPIs Huels/Wingo; contact PI: Huels)

Air pollution exposure is a well-established risk factor for many health conditions including dementia. Yet, how air pollution affects dementia is poorly understood. Here, we aim determine the role of air pollution on two of the most common causes of dementia, namely Alzheimer's disease and vascular cognitive impairment, using well-characterized diverse longitudinal studies of brain aging that will provide biological insights and identify characteristics for people at higher risk (e.g., sex and race/ethnicity).

Selected publications:

Casey E, Li Z, Liang D, Ebelt S, Levey AI, Lah JJ, Wingo TS, Hüls A. Association between Fine Particulate Matter Exposure and Cerebrospinal Fluid Biomarkers of Alzheimer’s Disease among a Cognitively Healthy Population-based Cohort. Environ Health Perspect. 2024 Apr;132(4):47001. doi: 10.1289/EHP13503. Epub 2024 Apr 3.*
Christensen GM*, Li Z*, Liang D, Ebelt S, Gearing M, Levey AI, Lah JJ, Wingo AP, Wingo TS, Hüls A. Association of PM2.5 Exposure and Alzheimer Disease Pathology in Brain Bank Donors-Effect Modification by APOE Genotype. Neurology. 2024 Mar 12;102(5):e209162. doi: 10.1212/WNL.0000000000209162. Epub 2024 Feb 21. (* equal contribution) *
Li Z, Liang D, Ebelt S, Gearing M, Kobor MS, Konwar C, Maclsaac JL, Dever K, Wingo AP, Levey AI, Lah JJ, Wingo TS, Hüls A. Differential DNA methylation in the brain as potential mediator of the association between traffic-related PM2.5 and neuropathology markers of Alzheimer's disease. Alzheimers Dement. 2024 Apr;20(4):2538-2551. doi: 10.1002/alz.13650. Epub 2024 Feb 12. *
Mei Y, Christensen GM, Li Z, Waller LA, Ebelt S, Marcus M, Lah JJ, Wingo AP, Wingo TS, Hüls A. Joint effects of air pollution and neighborhood socioeconomic status on cognitive decline - Mediation by depression, high cholesterol levels, and high blood pressure. Sci Total Environ. 2024 May 1;923:171535. doi: 10.1016/j.scitotenv.2024.171535. Epub 2024 Mar 6. *
Christensen GM, Li Z, Pearce J, Marcus M, Lah JJ, Waller LA, Ebelt S, Hüls A. The complex relationship of air pollution and neighborhood socioeconomic status and their association with cognitive decline. Environ Int. 2022 Sep 167:107416. doi: https://doi.org/10.1016/j.envint.2022.107416. *

Environmental Exposures and Brain Development

Collaboration with Heather Zar, Dan Stein, Aneesa Vanker and many other wonderful colleagues at the University of Cape Town &

Michael Kobor and his lab at the University of British Columbia

Recent publications:

Pruning and thresholding approach for methylation risk scores in multi-ancestry populations (peer-reviewed article)
DNA methylation as a potential mediator of the association between indoor air pollution and neurodevelopmental delay in a South African birth cohort (peer-reviewed article)
DNA methylation as a potential mediator of the association between prenatal tobacco and alcohol exposure and child neurodevelopment in a South African birth cohort (peer-reviewed article)
In-utero exposure to indoor air pollution or tobacco smoke and cognitive development in a South African birth cohort study (peer-reviewed article)

More information about the Drakenstein Child Health Study can be found here.

With the Drakenstein Child Health Study we are also part of the Pregnancy And Childhood Epigenetics (PACE) consortium, which is comprised of researchers at NIEHS and around the world who are interested in studying the early life environmental impacts on human disease using epigenetics.