# Molecular modulators of radiation-induced chromosome instability and hematopoietic damage

> **NIH NIH R01** · RBHS -CANCER INSTITUTE OF NEW JERSEY · 2021 · $375,299

## Abstract

Abstract
The hematopoietic system is one of the organ systems most vulnerable to radiation induced short-
and long- term damage. Efficient recovery from pathological or medically induced bone marrow
failure is dictated by the intrinsic sensitivity of the hematopoietic stem cell and the bone marrow
environment niche. Identification of molecules that affect hematopoietic recovery is essential to
the development of novel medical countermeasures against radiation damage. Our preliminary
studies suggested that loss of even a single copy of Bccip confers hypersensitivity of mice to
radiation-induced hematopoietic syndrome and lymphomagenesis, and the recruitment of BCCIP
to DNA damage sites are dependent on PARP1. We hypothesize that Bccip haploinsufficiency
can sensitize the hematopoietic stem cells to radiation killing, impair the long-term competency of
stem cell to reconstitute the hematopoietic system, and/or affect the bone marrow niche’s capacity
to nourish hematopoiesis. In Aim 1, a series of long-term and short-term experiments will be used
to determine whether Bccip haploinsufficiency enhances the killing of hematopoietic stem and
progenitor cells, impair stem cells’ capacity to reconstitute the bone marrow, and diminish the
ability of bone marrow niche to nourish the hematopoiesis. We also hypothesize that Bccip
haploinsufficiency alters the bone marrow progenitor cell susceptibility to tumor initiation and
subsequent tumor progression. In Aim 2, we will test this hypothesis by examining the tumor
clonality and defining the landscapes of chromosome rearrangements in the tumors formed in
wild type and Bccip haplo-insufficient mice using newly developed genomic and computational
approaches. In Aim 3, we will determine the PARylaiton dependent mechanism by which BCCIP
is recruited and retained at the DNA damage sites. Completion of these studies will elucidate a
unique role of Bccip in modulating hematopoiesis after radiation damage and in suppressing
radiation-induced tumorigenesis.

## Key facts

- **NIH application ID:** 10296435
- **Project number:** 2R01CA195612-06A1
- **Recipient organization:** RBHS -CANCER INSTITUTE OF NEW JERSEY
- **Principal Investigator:** Zhiyuan Shen
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $375,299
- **Award type:** 2
- **Project period:** 2015-05-01 → 2026-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10296435

## Citation

> US National Institutes of Health, RePORTER application 10296435, Molecular modulators of radiation-induced chromosome instability and hematopoietic damage (2R01CA195612-06A1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10296435. Licensed CC0.

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