# Ionizing radiation promotes clonal expansion of premalignant cells in the thymus

> **NIH NIH R00** · DUKE UNIVERSITY · 2020 · $248,999

## Abstract

PROJECT SUMMARY
Due to an ever-increasing number of cancer survivors, representing approximately 4.5% of the population in
the United States (2014), second malignancies related to chemotherapy and/or radiotherapy is a significant
concern in public health. However, underlying mechanisms of second malignancies are poorly understood.
While it is well known ionizing radiation can induce cancers in small animal models, whether radiation causes
second cancer by creating initiating mutations or by promoting the expansion of cells that harbor a pre-existing
mutation remains a field of active study. This knowledge gap represents a substantial barrier to assessing the
risk of second malignancies and to develop novel strategies for preventing or mitigating this clinically significant
side effect of cancer therapy. The long-term goal of this research is to study how ionizing radiation alters the
microenvironment and cell competition within the stem/progenitor pool to promote the development of second
hematological malignancies. To successfully launch my independent research program studying this question,
I will use this K99/R00 award to achieve my short-term objectives to 1) develop expertise in hematopoiesis and
thymopoiesis, 2) gain knowledge and skill sets studying epigenetic changes in the onset and progression of
radiation-induced thymic lymphoma, and 3) receive focused training in grant writing, leadership and career
development. These three objectives represent areas where continued development is crucial for my
successful transition to an independent investigator. The proposed research is innovative in that it challenges
the conventional view that radiation causes cancer predominantly by creating new mutations. Instead, this
proposal tests the hypothesis that radiation promotes the growth of cells with preexisting mutations. The
proposed research is significant because it will provide a mechanism for non-targeted effects of radiation-
induced carcinogenesis, which remains poorly understood for over 60 years. Ultimately, the conceptual
advances made possible by the proposed research will enable more complete understanding of mouse models
of radiation-induced thymic lymphoma and establish a preclinical platform for evaluating novel medical
countermeasures against radiation-induced hematological malignancies.

## Key facts

- **NIH application ID:** 9843493
- **Project number:** 5R00CA212198-05
- **Recipient organization:** DUKE UNIVERSITY
- **Principal Investigator:** Chang-Lung Lee
- **Activity code:** R00 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $248,999
- **Award type:** 5
- **Project period:** 2018-01-18 → 2020-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9843493

## Citation

> US National Institutes of Health, RePORTER application 9843493, Ionizing radiation promotes clonal expansion of premalignant cells in the thymus (5R00CA212198-05). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9843493. Licensed CC0.

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