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Principal Investigator: Baker, Tracie R
Institute Receiving Award University Of Florida
Location Gainesville, FL
Grant Number R01ES034878
Funding Organization National Institute of Environmental Health Sciences
Award Funding Period 17 Jan 2023 to 31 Oct 2027
DESCRIPTION (provided by applicant): PROJECT SUMMARY A single toxicant exposure during development can produce negative outcomes in adulthood and subsequent generations, presenting a major hurdle in the prevention and treatment of disease. In addition, given the susceptibility to toxicants amid degenerative biological and genetic processes, exposure during old age is a critical sensitive window. Despite their significance, however, the mechanisms that mediate both processes are poorly understood. Lead (Pb) remains one of ten World Health Organization-identified toxicants of major public health concern, even though there have been decades-long efforts to manage the routes of environmental exposure. Numerous studies have demonstrated potent neurotoxic effects of lead exposure on gene expression and the epigenome, resulting in outcomes such as impaired I.Q., behavioral dysregulation, and speech and learning deficits. Our long-term goal is to determine how environmental toxicants interfere with neurobehavior during critical windows so that evidence-based strategies to prevent and treat adult-onset and transgenerational disease can be developed. The overall objective for this NIEHS R01 Award (PA-20-185) application is to determine genome function alterations and epigenetic regulation of environmentally-influenced neurobehavioral phenotypes. The central hypothesis is that environmentally relevant Pb exposure during critical sensitive windows (early development and old age) lead to genomic and epigenetic dysregulation that alters neurogenesis pathway function in the exposed and subsequent generations. The rationale for the proposed research is that investigation of the mechanisms underlying Pb-induced outcomes will advance prevention, risk-assessment, diagnostic, and treatment strategies. Guided by strong preliminary data, this hypothesis will be tested by pursuing three specific aims: 1) Determine life stage-specific transcriptomic changes in neurogenesis pathways following developmental and geriatric exposure to environmentally relevant Pb levels; 2) Determine emergent changes in the epigenome related to phenotypic and genetic endpoints; 3) Determine multigenerational and transgenerational transcriptomic and epigenetic changes induced by ancestral exposure. Ultimately, these results will identify critical windows for biomarkers of effect, and inform the interplay among pathways mediating toxic endpoints.
Science Code(s)/Area of Science(s) Primary: 60 - Nervous System Research
Secondary: 03 - Carcinogenesis/Cell Transformation
Publications No publications associated with this grant
Program Officer Jonathan Hollander
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