# Protection of early embryogenesis and pluripotent stem cells against genetic parasites through a primitive immune system

> **NIH NIH R01** · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · 2020 · $351,713

## Abstract

PROJECT SUMMARY
Relics of mobile DNA make our genomes look like the aftermath of a mob scene. Even worse, some endogenous
retrotransposons did not die out, but rather still swarm our cells early in ontogeny. Their actions can seriously
damage the genome of the nascent embryo and cause sporadic diseases and infertility. Recently, we discovered
a mechanism by which neighboring cells actively remove pluripotent cells that fail to undergo silencing of their
endogenous retrotransposons. Our hypothesis is that there is a conditional policing mechanism reminiscent of a
primitive immune system. We propose that pluripotent stem cells sense the endogenous retroviral load of their
neighboring cells and, if it is higher than their own, act to kill and remove the overloaded cells. Upon completion
of the outlined work, we will have (i) probed a previously unexplored sensing mechanism that involves cells
“sniffing” one another for endogenous retroviruses and the removal of cells that failed to silence their genetic
parasites (Aims 1 and 2) and (ii) tested whether this system is tunable and subject to immune modulation (Aim
3). These outcomes will have a positive impact because they will force us to shift our attention away from solely
cell-intrinsic defense strategies towards considering a much more nuanced system in which cells constantly
monitor one another for endogenous retrotransposon-related health. Our line of investigation will provide new
targets for genetic diagnosis and interventions targeting pregnancy loss and infertility.

## Key facts

- **NIH application ID:** 9865734
- **Project number:** 1R01HD100518-01
- **Recipient organization:** ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
- **Principal Investigator:** Thomas P. Zwaka
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $351,713
- **Award type:** 1
- **Project period:** 2020-03-23 → 2025-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9865734

## Citation

> US National Institutes of Health, RePORTER application 9865734, Protection of early embryogenesis and pluripotent stem cells against genetic parasites through a primitive immune system (1R01HD100518-01). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9865734. Licensed CC0.

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