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Interactions of Environmental Chemical Mixtures, Genetics, and Immune Pathways in Autism Spectrum Disorder

Award Number: K99ES032481
ORGANIZATION: NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: TRAINING/TRAINEESHIP
PERIOD OF PERFORMANCE START DATE: 03/06/2021
PERIOD OF PERFORMANCE END DATE: 04/30/2023

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Interactions of Environmental Chemical Mixtures, Genetics, and Immune Pathways in Autism Spectrum Disorder - ABSTRACT The rising prevalence of Autism Spectrum Disorder (ASD) among children is a public health concern. An expanding landscape of genetic and environmental risk factors has been implicated in ASD’s development, indicating complex, multifactorial origins in early life. Many endocrine-disrupting chemicals (EDCs) have neurotoxic potential, but their role in ASD development needs clarification. EDCs are implicated in maternal immune dysregulation and inflammation, a leading research hypothesis of ASD’s developmental origins. Gene- environment investigations of EDCs, with focus on plausible biological mechanisms, could provide critical insight into whether genetic subgroups of individuals may be more sensitive to environmental chemicals and bring clarity to this inconsistent evidence between ASD and EDCs. The proposed research seeks to combine polygenic and complex environmental mixtures approaches to address gaps in understanding of ASD’s etiology. During the K99 phase of this award, I will pursue didactic and mentored training in autism epidemiology, immunology, and methodologies of analyzing complex environmental mixtures, genome-wide data, and gene-environment interplay. Under the mentorship of a strong multidisciplinary team with a history of collaboration, I will apply this training to studies of the relationships between environmental, immunologic, and genetic data from the Early Markers for Autism study (EMA; R01ES016669, PI: Croen), a population-based case-control study (n=1005). In Aim 1, I will apply training in complex mixtures methods to examine the pathway between joint exposure to multiple EDCs during gestation, biomarkers of maternal and neonatal immune function, and child ASD. In Aim 2, I will apply training in genome-wide analysis to identify maternal and fetal genetic variants associated with mixtures of EDCs in mid-pregnancy circulation. In the K00 phase (Aim 3), I will harness these new analytical skills to conduct a GxE analysis of the association of EDCs and polygenic risk on early life immune function and ASD development. I will conduct Aim 3 in EMA with replication in two larger mother-child cohort studies. The long-term goal of this research is to identify modifiable risk factors and key biological pathways in ASD which can inform not only interventions to lower neurotoxic exposures in pregnant mothers and infants but also pharmacologic interventions targeting the immune and other physiologic intermediates. These training and research activities will serve as the springboard for developing a competitive R01 application and launching my independent career in autism epidemiology.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2024 ( Subtotal = -$7,267 )
2024	2022	KAISER FOUNDATION HOSPITALS	1800 HARRISON ST FL 16	OAKLAND	CA	94612	ALAMEDA	USA	Environmental Health	000	2	3/7/2024	NON-COMPETING CONTINUATION	-$7,267
														Subtotal = -$7,267

Issue Date FY: 2023 ( Subtotal = $0 )
2023	2022	KAISER FOUNDATION HOSPITALS	1800 HARRISON ST FL 16	OAKLAND	CA	94612	ALAMEDA	USA	Environmental Health	000	2	2/15/2023	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2022 ( Subtotal = $122,801 )
2022	2022	KAISER FOUNDATION HOSPITALS	1800 HARRISON ST FL 16	OAKLAND	CA	94612	ALAMEDA	USA	Environmental Health	000	2	3/1/2022	NON-COMPETING CONTINUATION	$122,801
														Subtotal = $122,801

Issue Date FY: 2021 ( Subtotal = $122,801 )
2021	2021	KAISER FOUNDATION HOSPITALS	1800 HARRISON ST FL 16	OAKLAND	CA	94612	ALAMEDA	USA	Environmental Health	000	1	3/5/2021	NEW	$122,801
														Subtotal = $122,801

Grand Total All Awards = $238,335

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Interactions of Environmental Chemical Mixtures, Genetics, and Immune Pathways in Autism Spectrum Disorder

Award Number: K99ES032481

ORGANIZATION: NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: TRAINING/TRAINEESHIP

PERIOD OF PERFORMANCE START DATE: 03/06/2021

PERIOD OF PERFORMANCE END DATE: 04/30/2023

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