Scholars@Duke
Chang Lung Lee

Chang Lung Lee

Associate Professor in Radiation Oncology
Radiation Oncology
chang-lung.lee@duke.edu
Box 91006, Durham, NC 27708
B220 LSRC Bldg, 308 Research Dr, Box 91006, Durham, NC 27708

Selected Publications

Impact of cancer therapy on clonal hematopoiesis mutations and subsequent clinical outcomes.

Journal Article Blood Adv · October 8, 2024 Exposure to cancer therapies is associated with an increased risk of clonal hematopoiesis (CH). The objective of our study was to investigate the genesis and evolution of CH after cancer therapy. In this prospective study, we undertook error-corrected dupl ... Full text Link to item Cite

Mechanisms Underlying the Development of Murine T-Cell Lymphoblastic Lymphoma/Leukemia Induced by Total-Body Irradiation.

Journal Article Cancers (Basel) · June 14, 2024 Exposure to ionizing radiation is associated with an increased risk of hematologic malignancies in myeloid and lymphoid lineages in humans and experimental mice. Given that substantial evidence links radiation exposure with the risk of hematologic malignan ... Full text Link to item Cite

Imaging Assessment of Radiation Therapy-Related Normal Tissue Injury in Children: A PENTEC Visionary Statement.

Journal Article Int J Radiat Oncol Biol Phys · June 1, 2024 The Pediatric Normal Tissue Effects in the Clinic (PENTEC) consortium has made significant contributions to understanding and mitigating the adverse effects of childhood cancer therapy. This review addresses the role of diagnostic imaging in detecting, scr ... Full text Link to item Cite

p53 promotes revival stem cells in the regenerating intestine after severe radiation injury.

Journal Article Nat Commun · April 8, 2024 Ionizing radiation induces cell death in the gastrointestinal (GI) epithelium by activating p53. However, p53 also prevents animal lethality caused by radiation-induced acute GI syndrome. Through single-cell RNA-sequencing of the irradiated mouse small int ... Full text Link to item Cite

Temporary Knockdown of p53 During Focal Limb Irradiation Increases the Development of Sarcomas.

Journal Article Cancer Res Commun · December 5, 2023 UNLABELLED: Approximately half of patients with cancer receive radiotherapy and, as cancer survivorship increases, the low rate of radiation-associated sarcomas is rising. Pharmacologic inhibition of p53 has been proposed as an approach to ameliorate acute ... Full text Link to item Cite

Characterizing the role of Phlda3 in the development of acute toxicity and malignant transformation of hematopoietic cells induced by total-body irradiation in mice.

Journal Article Sci Rep · August 9, 2023 The tumor suppressor p53 is a transcriptional factor that plays a crucial role in controlling acute toxicity and long-term malignant transformation of hematopoietic cells induced by genotoxic stress such as ionizing radiation. Among all transcriptional tar ... Full text Link to item Cite

p53 promotes revival stem cells in the regenerating intestine after severe radiation injury.

Journal Article bioRxiv · April 28, 2023 UNLABELLED: Ionizing radiation induces cell death in the gastrointestinal (GI) epithelium by activating p53. However, p53 also prevents animal lethality caused by radiation-induced GI injury. Through single-cell RNA-sequencing of the irradiated mouse intes ... Full text Link to item Cite

Data from Selective ERBB2 and BCL2 Inhibition Is Synergistic for Mitochondrial-Mediated Apoptosis in MDS and AML Cells

Other · April 3, 2023 <div>Abstract<p>The <i>ERBB2</i> proto-oncogene is associated with an aggressive phenotype in breast cancer. Its role in hematologic malignancies is incompletely defined, in part because <i>ERBB2</i> is not readi ... Full text Cite

Data from Whole-Exome Sequencing of Radiation-Induced Thymic Lymphoma in Mouse Models Identifies Notch1 Activation as a Driver of p53 Wild-Type Lymphoma

Other · March 31, 2023 <div>Abstract<p>Mouse models of radiation-induced thymic lymphoma are widely used to study the development of radiation-induced blood cancers and to gain insights into the biology of human T-cell lymphoblastic leukemia/lymphoma. Here we ... Full text Cite

Histological assessment of intestinal injury by ionizing radiation.

Chapter · 2023 Given the potential risk of radiological terrorism and disasters, it is essential to develop plans to prepare for such events. In these hazardous scenarios, radiation-induced gastrointestinal (GI) syndrome is one of the many manifestations that may happen ... Full text Link to item Cite

The p53 Transactivation Domain 1-Dependent Response to Acute DNA Damage in Endothelial Cells Protects against Radiation-Induced Cardiac Injury.

Journal Article Radiat Res · August 1, 2022 Thoracic radiation therapy can cause endothelial injury in the heart, leading to cardiac dysfunction and heart failure. Although it has been demonstrated that the tumor suppressor p53 functions in endothelial cells to prevent the development of radiation-i ... Full text Link to item Cite

Investigating the Role of Inflammasome Caspases 1 and 11 in the Acute Radiation Syndrome.

Journal Article Radiat Res · December 1, 2021 Exposure to high dose radiation causes life-threatening acute and delayed effects. Defining the mechanisms of lethal radiation-induced acute toxicity of gastrointestinal and hematopoietic tissues are critical steps to identify drug targets to mitigate and ... Full text Link to item Cite

Sensitization of Endothelial Cells to Ionizing Radiation Exacerbates Delayed Radiation Myelopathy in Mice.

Journal Article Radiation research · November 2021 Delayed radiation myelopathy is a rare, but significant late side effect from radiation therapy that can lead to paralysis. The cellular and molecular mechanisms leading to delayed radiation myelopathy are not completely understood but may be a consequence ... Full text Cite

Whole-Exome Sequencing of Radiation-Induced Thymic Lymphoma in Mouse Models Identifies Notch1 Activation as a Driver of p53 Wild-Type Lymphoma.

Journal Article Cancer Res · July 15, 2021 Mouse models of radiation-induced thymic lymphoma are widely used to study the development of radiation-induced blood cancers and to gain insights into the biology of human T-cell lymphoblastic leukemia/lymphoma. Here we aimed to identify key oncogenic dri ... Full text Link to item Cite

Selective ERBB2 and BCL2 Inhibition Is Synergistic for Mitochondrial-Mediated Apoptosis in MDS and AML Cells.

Journal Article Mol Cancer Res · May 2021 The ERBB2 proto-oncogene is associated with an aggressive phenotype in breast cancer. Its role in hematologic malignancies is incompletely defined, in part because ERBB2 is not readily detected on the surface of cancer cells. We demonstrate that truncated ... Full text Link to item Cite

Characterization of cardiovascular injury in mice following partial-heart irradiation with clinically relevant dose and fractionation.

Journal Article Radiother Oncol · April 2021 BACKGROUND AND PURPOSE: Late cardiac toxicity is a major side effect of radiation therapy (RT) for breast cancer. We developed and characterized a mouse model of radiation-induced heart disease that mimics the dose, fractionation, and beam arrangement of l ... Full text Link to item Cite

Transplantation of Unirradiated Bone Marrow Cells after Total-Body Irradiation Prevents the Development of Thymic Lymphoma in Mice through Niche Competition.

Journal Article Radiat Res · March 1, 2021 Mouse models of radiation-induced thymic lymphoma are commonly used to study the biological effects of total-body irradiation (TBI) on the formation of hematologic malignancies. It is well documented that radiation-induced thymic lymphoma can be inhibited ... Full text Link to item Cite

Epithelial Regeneration After Doxorubicin Arises Primarily From Early Progeny of Active Intestinal Stem Cells.

Journal Article Cell Mol Gastroenterol Hepatol · 2021 BACKGROUND & AIMS: aISCs (aISCs) are sensitive to acute insults including chemotherapy and irradiation. Regeneration after aISC depletion has primarily been explored in irradiation (IR). However, the cellular origin of epithelial regeneration after doxorub ... Full text Link to item Cite

The p53 transactivation domain 1-dependent response to acute DNA damage in endothelial cells protects against radiation-induced cardiac injury

Journal Article · 2021 Thoracic radiation therapy can cause endothelial injury in the heart, leading to cardiac dysfunction and heart failure. Although it has been demonstrated that the tumor suppressor p53 functions in endothelial cells to prevent the development of radiation-i ... Full text Cite

Inhibiting Glycogen Synthase Kinase-3 Mitigates the Hematopoietic Acute Radiation Syndrome in a Sex- and Strain-dependent Manner in Mice.

Journal Article Health Phys · September 2020 The Radiation and Nuclear Countermeasures Program at the National Institute of Allergy and Infectious Diseases (NIAID) mandated that medical countermeasures for treating Acute Radiation Syndrome (ARS) must have efficacy when administered at least 24 h afte ... Full text Link to item Cite

Activation of Notch1 drives the development of radiation-induced thymic lymphoma in p53 wild-type mice

Journal Article · 2020 ABSTRACT Mouse models of radiation-induced thymic lymphoma are widely used to study the development of radiation-induced blood cancers and to gain insights into the biology of human T-lymphoblastic leukemia/lymphoma. Here, we aimed to determine ke ... Full text Cite

Tracing Tumor Evolution in Sarcoma Reveals Clonal Origin of Advanced Metastasis.

Journal Article Cell Rep · September 10, 2019 Cellular heterogeneity is frequently observed in cancer, but the biological significance of heterogeneous tumor clones is not well defined. Using multicolor reporters and CRISPR-Cas9 barcoding, we trace clonal dynamics in a mouse model of sarcoma. We show ... Full text Link to item Cite

Sensitization of Vascular Endothelial Cells to Ionizing Radiation Promotes the Development of Delayed Intestinal Injury in Mice.

Journal Article Radiat Res · September 2019 Exposure of the gastrointestinal (GI) tract to ionizing radiation can cause acute and delayed injury. However, critical cellular targets that regulate the development of radiation-induced GI injury remain incompletely understood. Here, we investigated the ... Full text Open Access Link to item Cite

Mutational landscape in genetically engineered, carcinogen-induced, and radiation-induced mouse sarcoma.

Journal Article JCI Insight · July 11, 2019 Cancer development is influenced by hereditary mutations, somatic mutations due to random errors in DNA replication, or external factors. It remains unclear how distinct cell-intrinsic and -extrinsic factors impact oncogenesis within the same tissue type. ... Full text Link to item Cite

Photon-counting cine-cardiac CT in the mouse

Journal Article · June 4, 2019 Abstract The maturation of photon-counting detector (PCD) technology promises to enhance routine CT imaging applications with high-fidelity spectral information. In this paper, we demonstrate the power of this synergy and our complementary reconstruction t ... Full text Cite

Deletion of Atm in Tumor but not Endothelial Cells Improves Radiation Response in a Primary Mouse Model of Lung Adenocarcinoma.

Journal Article Cancer Res · February 15, 2019 Stereotactic body radiotherapy is utilized to treat lung cancer. The mechanism of tumor response to high-dose radiotherapy (HDRT) is controversial, with competing hypotheses of increased direct tumor cell killing versus indirect effects on stroma including ... Full text Link to item Cite

Photon-counting cine-cardiac CT in the mouse.

Journal Article PLoS One · 2019 The maturation of photon-counting detector (PCD) technology promises to enhance routine CT imaging applications with high-fidelity spectral information. In this paper, we demonstrate the power of this synergy and our complementary reconstruction techniques ... Full text Open Access Link to item Cite

Blocking Cyclin-Dependent Kinase 4/6 During Single Dose Versus Fractionated Radiation Therapy Leads to Opposite Effects on Acute Gastrointestinal Toxicity in Mice.

Journal Article Int J Radiat Oncol Biol Phys · December 1, 2018 PURPOSE: The delivery of radiation therapy to cure gastrointestinal (GI) cancers is often limited by normal tissue toxicity of the GI tract. Studies using genetically engineered mice have demonstrated an essential role of the cyclin-dependent kinase inhibi ... Full text Link to item Cite

Notch-Induced Myeloid Reprogramming in Spontaneous Pancreatic Ductal Adenocarcinoma by Dual Genetic Targeting.

Journal Article Cancer Res · September 1, 2018 Despite advances in our understanding of the genetics of pancreatic ductal adenocarcinoma (PDAC), the efficacy of therapeutic regimens targeting aberrant signaling pathways remains highly limited. Therapeutic strategies are greatly hampered by the extensiv ... Full text Link to item Cite

Mice Lacking RIP3 Kinase are not Protected from Acute Radiation Syndrome.

Journal Article Radiat Res · June 2018 Exposure to high doses of ionizing radiation can cause lethal injury to normal tissue, thus inducing acute radiation syndrome. Acute radiation syndrome is caused by depletion of bone marrow cells (hematopoietic syndrome) and irreparable damage to the epith ... Full text Link to item Cite

Characterizing the Potency and Impact of Carbon Ion Therapy in a Primary Mouse Model of Soft Tissue Sarcoma.

Journal Article Mol Cancer Ther · April 2018 Carbon ion therapy (CIT) offers several potential advantages for treating cancers compared with X-ray and proton radiotherapy, including increased biological efficacy and more conformal dosimetry. However, CIT potency has not been characterized in primary ... Full text Link to item Cite

NF1+/- Hematopoietic Cells Accelerate Malignant Peripheral Nerve Sheath Tumor Development without Altering Chemotherapy Response.

Journal Article Cancer Res · August 15, 2017 Haploinsufficiency in the tumor suppressor NF1 contributes to the pathobiology of neurofibromatosis type 1, but a related role has not been established in malignant peripheral nerve sheath tumors (MPNST) where NF1 mutations also occur. Patients with NF1-as ... Full text Link to item Cite

An extra copy of p53 suppresses development of spontaneous Kras-driven but not radiation-induced cancer.

Journal Article JCI Insight · July 7, 2016 The tumor suppressor p53 blocks tumor progression in multiple tumor types. Radiation-induced cancer following exposure to radiation therapy or space travel may also be regulated by p53 because p53 has been proposed to respond to DNA damage to suppress tumo ... Full text Link to item Cite

A mouse-human phase 1 co-clinical trial of a protease-activated fluorescent probe for imaging cancer.

Journal Article Sci Transl Med · January 6, 2016 Local recurrence is a common cause of treatment failure for patients with solid tumors. Intraoperative detection of microscopic residual cancer in the tumor bed could be used to decrease the risk of a positive surgical margin, reduce rates of reexcision, a ... Full text Link to item Cite

Spectrotemporal CT data acquisition and reconstruction at low dose.

Journal Article Med Phys · November 2015 PURPOSE: X-ray computed tomography (CT) is widely used, both clinically and preclinically, for fast, high-resolution anatomic imaging; however, compelling opportunities exist to expand its use in functional imaging applications. For instance, spectral info ... Full text Open Access Link to item Cite

Acute DNA damage activates the tumour suppressor p53 to promote radiation-induced lymphoma.

Journal Article Nat Commun · September 24, 2015 Featured Publication Genotoxic cancer therapies, such as chemoradiation, cause haematological toxicity primarily by activating the tumour suppressor p53. While inhibiting p53-mediated cell death during cancer therapy ameliorates haematologic toxicity, whether it also impacts c ... Full text Link to item Cite

Tumor cells, but not endothelial cells, mediate eradication of primary sarcomas by stereotactic body radiation therapy.

Journal Article Sci Transl Med · March 11, 2015 Cancer clinics currently use high-dose stereotactic body radiation therapy as a curative treatment for several kinds of cancers. However, the contribution of vascular endothelial cells to tumor response to radiation remains controversial. Using dual recomb ... Full text Link to item Cite

Rank-sparsity constrained, spectro-temporal reconstruction for retrospectively gated, dynamic CT

Conference Progress in Biomedical Optics and Imaging - Proceedings of SPIE · January 1, 2015 Relative to prospective projection gating, retrospective projection gating for dynamic CT applications allows fast imaging times, minimizing the potential for physiological and anatomic variability. Preclinically, fast imaging is attractive due to the rapi ... Full text Cite

A next-generation dual-recombinase system for time- and host-specific targeting of pancreatic cancer.

Journal Article Nat Med · November 2014 Genetically engineered mouse models (GEMMs) have dramatically improved our understanding of tumor evolution and therapeutic resistance. However, sequential genetic manipulation of gene expression and targeting of the host is almost impossible using convent ... Full text Link to item Cite

MicroRNA-182 drives metastasis of primary sarcomas by targeting multiple genes.

Journal Article J Clin Invest · October 2014 Metastasis causes most cancer deaths, but is incompletely understood. MicroRNAs can regulate metastasis, but it is not known whether a single miRNA can regulate metastasis in primary cancer models in vivo. We compared the expression of miRNAs in metastatic ... Full text Link to item Cite

Atm deletion with dual recombinase technology preferentially radiosensitizes tumor endothelium.

Journal Article J Clin Invest · August 2014 Featured Publication Cells isolated from patients with ataxia telangiectasia are exquisitely sensitive to ionizing radiation. Kinase inhibitors of ATM, the gene mutated in ataxia telangiectasia, can sensitize tumor cells to radiation therapy, but concern that inhibiting ATM in ... Full text Link to item Cite

Reining in radiation injury: HIF2α in the gut.

Journal Article Sci Transl Med · May 14, 2014 Deletion of prolyl hydroxylase domain proteins or overexpression of hypoxia-inducible factor 2α (HIF2α) in the gastrointestinal epithelium improves survival of mice after abdominal irradiation (Taniguchi et al., this issue). ... Full text Link to item Cite

Inhibiting glycogen synthase kinase-3 mitigates the hematopoietic acute radiation syndrome in mice.

Journal Article Radiat Res · May 2014 Exposure to a nuclear accident or radiological attack can cause death from acute radiation syndrome (ARS), which results from radiation injury to vital organs such as the hematopoietic system. However, the U.S. Food and Drug Administration (FDA) has not ap ... Full text Link to item Cite

Assessing cardiac injury in mice with dual energy-microCT, 4D-microCT, and microSPECT imaging after partial heart irradiation.

Journal Article Int J Radiat Oncol Biol Phys · March 1, 2014 PURPOSE: To develop a mouse model of cardiac injury after partial heart irradiation (PHI) and to test whether dual energy (DE)-microCT and 4-dimensional (4D)-microCT can be used to assess cardiac injury after PHI to complement myocardial perfusion imaging ... Full text Open Access Link to item Cite

Role of p53 in regulating tissue response to radiation by mechanisms independent of apoptosis.

Journal Article Transl Cancer Res · October 2013 Radiation exposure leads to diverse outcomes in vivo across different tissues and even within the same cell lineage. The diversity of radiation response in vivo is at least partially attributable to the status of the tumor suppressor p53, a master regulato ... Link to item Cite

Assessing the radiation response of lung cancer with different gene mutations using genetically engineered mice.

Journal Article Front Oncol · 2013 PURPOSE: Non-small cell lung cancers (NSCLC) are a heterogeneous group of carcinomas harboring a variety of different gene mutations. We have utilized two distinct genetically engineered mouse models of human NSCLC (adenocarcinoma) to investigate how genet ... Full text Open Access Link to item Cite

Intraoperative detection and removal of microscopic residual sarcoma using wide-field imaging.

Journal Article Cancer · November 1, 2012 BACKGROUND: The goal of limb-sparing surgery for a soft tissue sarcoma of the extremity is to remove all malignant cells while preserving limb function. After initial surgery, microscopic residual disease in the tumor bed will cause a local recurrence in a ... Full text Link to item Cite

p53 functions in endothelial cells to prevent radiation-induced myocardial injury in mice.

Journal Article Sci Signal · July 24, 2012 Featured Publication Radiation therapy, which is used for the treatment of some cancers, can cause delayed heart damage. In the heart, p53 influences myocardial injury that occurs after multiple types of stress. Here, we demonstrated that p53 functioned in endothelial cells to ... Full text Link to item Cite

Generation of primary tumors with Flp recombinase in FRT-flanked p53 mice.

Journal Article Dis Model Mech · May 2012 Featured Publication The site-specific recombinases Cre and Flp can mutate genes in a spatially and temporally restricted manner in mice. Conditional recombination of the tumor suppressor gene p53 using the Cre-loxP system has led to the development of multiple genetically eng ... Full text Link to item Cite

p21 protects "Super p53" mice from the radiation-induced gastrointestinal syndrome.

Journal Article Radiat Res · March 2012 Exposure of the gastrointestinal (GI) tract to high doses of radiation can lead to lethality from the GI syndrome. Although the molecular mechanism regulating the GI syndrome remains to be fully defined, we have recently demonstrated that p53 within the GI ... Full text Link to item Cite

Molecular analyses of the Arabidopsis TUBBY-like protein gene family.

Journal Article Plant Physiol · April 2004 In mammals, TUBBY-like proteins play an important role in maintenance and function of neuronal cells during postdifferentiation and development. We have identified a TUBBY-like protein gene family with 11 members in Arabidopsis, named AtTLP1-11. Although s ... Full text Link to item Cite