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Impact of Phthalate Exposure on Telomere Biology in Utero

Award Number: R01ES035760
ORGANIZATION: NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 04/03/2024
PERIOD OF PERFORMANCE END DATE: 01/31/2029

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Impact of Phthalate Exposure on Telomere Biology in Utero - This proposal posits that phthalates, which are widely considered endocrine disrupting chemicals, interfere with human telomere biology in utero, leading to shortening of telomeres in the placenta and newborn. Specifically, it is hypothesized that phthalates alter the activity of telomerase through actions on hTERT, which encodes the catalytic subunit of the enzyme. As telomere length (TL) is largely determined at birth, prenatal exposure to phthalates could reset one’s lifelong TL trajectory with potential health effects during adulthood. Southern blotting (SB) and the Telomeres Shortest Length Assay (TeSLA) will be used to examine associations between prenatal phthalate exposure and TL parameters measured in the placenta-newborn unit. The placenta will further be leveraged to gain a mechanistic understanding of molecular outcomes related to phthalate exposure. This will be achieved by quantifying hTERT expression, telomerase activity, formation of telomere dysfunction- induced DNA damage foci (TIF), activation of cell cycle checkpoints and senescence markers in tandem with measuring TL parameters. TL measurements in umbilical cord blood and follow-up blood at approximately age 8 years will serve to test whether a putative phthalate effect on TL persists through the first decade of life. Generating longitudinal TL data will not only provide insight into the endurance of the phthalate effect, but will also fill a critical knowledge gap about early life TL dynamics. This research will leverage existing prenatal phthalate data and biobanked perinatal biospecimens (placenta and cord blood) from 500 mother-child pairs enrolled in the prospective New York University Children’s Health and Environment Study (NYU CHES). The proposal benefits from the strong collaboration between W. Cowell (Contact PI), an environmental and molecular epidemiologist with over 10 years of experience working with birth cohorts and A. Aviv (Co-PI), an expert in telomere biology. Knowledge gained can provide a foundation for the use of TL at birth as a biomarker of future health risk. TL measurements may thus become a precision tool that help gauge early risk for later life TL-linked diseases.


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: 2025 ( Subtotal = $359,000 )
2025	2025	NEW YORK UNIVERSITY	550 1ST AVE	NEW YORK	NY	10016	NEW YORK	USA	Environmental Health	000	2	1/27/2025	NON-COMPETING CONTINUATION	$359,000
														Subtotal = $359,000

Issue Date FY: 2024 ( Subtotal = $359,000 )
2024	2024	NEW YORK UNIVERSITY	550 1ST AVE	NEW YORK	NY	10016	NEW YORK	USA	Environmental Health	000	1	4/2/2024	NEW	$359,000
														Subtotal = $359,000

Grand Total All Awards = $718,000

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Impact of Phthalate Exposure on Telomere Biology in Utero

Award Number: R01ES035760

ORGANIZATION: NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 04/03/2024

PERIOD OF PERFORMANCE END DATE: 01/31/2029

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