Placental genomics in the developmental consequences of marijuana use in pregnancy

Active Project Grant Awarded Last action

Award ID
R01DA056787
Recipient
Awarding agency
Obligated
$3,838,202

Award facts

Assistance listing
93.279 Drug Use and Addiction Research Programs
Completion date 70% complete
Place of performance
Providence, RI 02906, USA

Award details come from USAspending.gov.

Description

As the agency reported it.

Abstract
This application is responsive to not-DA-20-039: effects of cannabis use and cannabinoids on the devel- oping brain. Prenatal cannabis use is common and increasing, with rates as high as 1 in 4 in poor, young, underserved women. Expanding legalization of cannabis has led to increasing availability, use, perceptions of safety as well as increased potency. However, data is lacking regarding the impact of prenatal use of increase- ED-potency cannabis on offspring neurodevelopment. Our group is currently conducting an intensive, prospective investigation of the impact of maternal prenatal cannabis use on infant neurodevelopment (R01DA044504). Our ongoing study has yielded preliminary evidence for an impact of prenatal cannabis on offspring growth and neurodevelopment, but does not involve a comprehensive interrogation of genomic pathways underlying these associations. Pinpointing genomic pathways will allow US to identify biomarkers of fetal harm and develop novel screening tools and intervention targets to protect and treat exposed offspring. The placenta is a unique organ that regulates the intrauterine environment, maternal-fetal communication – including passage of cannabinoids – and plays a critical role in supporting fetal growth and neurodevelopment. Seminal work by our group has revealed that the prenatal environment impacts placenta function, that alterations in placenta function can be informed by genomic profiling of the placenta, and that alterations in placenta genomic profiles are linked to newborn growth and neurobehavior. Micrornas (mirnas) are an understudied aspect of placenta epigenetic regulation; mirnas are short non-coding rnas that regulate gene expression post-transcriptionally and are crit- ical regulators of placental- and neuro-development. A recent initial study supports the hypothesis that maternal cannabis may impact placenta immune gene networks, and offspring anxiety, but was not designed to investigate prenatal cannabis, only included a small number of cannabis users, and did not include mirna. We propose a comprehensive placenta mirna and mrna profiling study to define the impact of prenatal cannabis exposure on placenta genomic activity and infant neurodevelopment. We test the central hypothesis that prenatal cannabis exposure leads to unique alterations in placenta endocannabinoid, neuronal development, immune, and stress signaling pathways, and that these functional genomic features will also impact infant DE- velopment. We leverage our ongoing cohort (n=100 cannabis users, n=100 non-users) designed to assess the impact of prenatal cannabis on infant neurodevelopment and including placenta collection for candidate methyl- ation assays. Our proposed genomic mechanisms study involves the addition of state-of-the-art whole transcrip- tome RNA-sequencing (mrna and mirna) to delineate the functional impacts of prenatal cannabis exposure and links to infant development. Determining genomic profiles underlying the impact of prenatal cannabis on infant development is timely and offers potential to identify biomarkers of exposure and offspring risk as well as molecular targets for future intervention efforts.

Transactions

Action Obligated Date
Amendment $675,274
Amendment $670,620
Amendment $642,372
Amendment $642,372
Amendment $603,782
Original award $603,782

Subawards

Subrecipient Amount Awarded
Emory University Placental Genomics in the Developmental Consequences of Marijuana Use in Pregnancy $399,075
Women & Infants Hospital Of Rhode Island $30,909
Emory University Placental Genomics in the Developmental Consequences of Marijuana use in Pregnancy $391,250
Emory University Placental Genomics in the Developmental Consequences of Marijuana Use in Pregnancy $354,056
Emory University $352,125

Quick answers

Who received award R01DA056787?

R01DA056787 was awarded to The Miriam Hospital by National Institute on Drug Abuse (National Institutes of Health) on June 1, 2023.

How much is award R01DA056787 worth?

$3,838,202 has been obligated on R01DA056787.

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