Christophe Badie

Christophe Badie
Public Health England | HPA · Cancer Mechanisms and Biomarkers-Radiation Effects department-Centre for Radiation, Chemical and Environmental Hazards (CRCE)

PhD

About

148
Publications
26,961
Reads
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2,936
Citations
Citations since 2016
95 Research Items
1880 Citations
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Introduction
My work focus on two areas: 1.Research into the chromosomal and molecular mechanisms that underlie leukaemia initiation and development and investigate specific genetic factors that influence haematopoietic cell radiosensitivity and cancer susceptibility. Studies of the early events in radiation carcinogenesis are important in the context of developing mechanistic models for cancer risk estimation. 2. New biomarkers of exposure and long term effects focising on transcrptional modification.
Additional affiliations
April 2013 - present
Public Health England
Position
  • Scientific group leader
April 2013 - February 2016
Public Health England
Position
  • Scientific group leader
January 2005 - present
Public Health England

Publications

Publications (148)
Article
Full-text available
Purpose The concept of the adverse outcome pathway (AOP) has recently gained significant attention as to its potential for incorporation of mechanistic biological information into the assessment of adverse health outcomes following ionizing radiation (IR) exposure. This work is an account of the activities of an international expert group formed sp...
Article
Full-text available
In vitro experiments show that the cells possibly responsible for radiation-induced acute myeloid leukemia (rAML) exhibit low-dose hyper-radiosensitivity (HRS). In these cells, HRS is responsible for excess cell killing at low doses. Besides the endpoint of cell killing, HRS has also been shown to stimulate the low-dose formation of chromosomal abe...
Article
Introduction The biological effects of chronic, low dose radiation, to which operators performing fluoroscopy-guided procedures are exposed, are unknown. We have previously demonstrated acute DNA damage/repair in lymphocytes from operators performing fluoroscopy-guided endovascular aneurysm repair (EVAR), but these markers normalised after 24 hours...
Article
Full-text available
The aim of this review is to investigate the literature pertaining to the potential risks of low-dose ionizing radiation to Lynch syndrome patients by use of computed tomography (CT), either diagnostic CT colonography (CTC), standard staging CT or CT surveillance. Furthermore, this review explores the potential risks of using radiotherapy for treat...
Chapter
T cells play an essential role in defense of the organism against pathogens and cancer. Efficient protection requires a vast repertoire of immune receptors, which is created by the V(D)J recombination process. There are multiple algorithms designed for the annotation of recombined T cell receptor (TR) sequences from traditional (short-read) RNA-Seq...
Article
Full-text available
External beam radiation therapy leads to cellular activation of the DNA damage response (DDR). DNA double-strand breaks (DSBs) activate the ATM/CHEK2/p53 pathway, inducing the transcription of stress genes. The dynamic nature of this transcriptional response has not been directly observed in vivo in humans. In this study we monitored the messenger...
Article
Full-text available
Haematopoietic bone marrow cells are amongst the most sensitive to ionizing radiation (IR), initially resulting in cell death or genotoxicity that may later lead to leukaemia development, most frequently Acute Myeloid Leukaemia (AML). The target cells for radiation-induced Acute Myeloid Leukaemia (rAML) are believed to lie in the haematopoietic ste...
Article
Full-text available
Purpose In a nuclear or radiological event, an early diagnostic or prognostic tool is needed to distinguish unexposed from low- and highly-exposed individuals with the latter requiring early and intensive medical care. Radiation-induced gene expression (GE) changes observed within hours and days after irradiation have shown potential to serve as bi...
Article
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The quest for the discovery and validation of radiosensitivity biomarkers is ongoing and while conventional bioassays are well established as biomarkers, molecular advances have unveiled new emerging biomarkers. Herein, we present the validation of a new 4-gene signature panel of CDKN1, FDXR, SESN1 and PCNA previously reported to be radiation-respo...
Chapter
DNA methylation alteration is crucial for the initiation and development of Acute Myeloid Leukemia. However, only a few epigenetic biomarkers of AML have been discovered so far. DNA methylation of CpG rich gene promoters has the highest impact on gene expression level, so biomarkers should be sought in these genomic regions. Principal Component Ana...
Article
Full-text available
Humans have learned to harness the power of radiation for therapeutic ends, with 50% of all patients diagnosed with cancer undergoing radiotherapy as part of their treatment [...]
Article
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Large-scale radiation emergency scenarios involving protracted low dose rate radiation exposure (e.g. a hidden radioactive source in a train) necessitate the development of high throughput methods for providing rapid individual dose estimates. During the RENEB (Running the European Network of Biodosimetry) 2019 exercise, four EDTA-blood samples wer...
Article
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Background This communication reports the identification of a new panel of transcriptional changes in inflammation-associated genes observed in response to ionising radiation received by radiotherapy patients. Methods Peripheral blood samples were taken with ethical approval and informed consent from a total of 20 patients undergoing external beam...
Article
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In the past decade, radiation therapy (RT) entered the era of personalized medicine, following the striking improvements in radiation delivery and treatment planning optimization, and in the understanding of the cancer response, including the immunological response. The next challenge is to identify the optimal radiation regimen(s) to induce a clin...
Article
Purpose For triage purposes following a nuclear accident or a terrorist event, gene expression biomarkers in blood have been demonstrated to be good bioindicators of ionizing radiation (IR) exposure and can be used to assess the dose received by exposed individuals. Many IR-sensitive genes are regulated by the DNA damage response pathway, and modul...
Article
Full-text available
The effect of low-dose ionizing radiation exposure on leukemia incidence remains poorly understood. Possible dose-response curves for various forms of leukemia are largely based on cohorts of atomic bomb survivors. Animal studies can contribute to an improved understanding of radiation-induced acute myeloid leukemia (rAML) in humans. In male CBA/H...
Preprint
Full-text available
This communication reports the identification of a new panel of transcriptional changes in inflammation-associated genes observed in response to ionising radiation received by radiotherapy patients. Peripheral blood samples were taken with ethical approval and informed consent from a total of 20 patients undergoing external beam radiotherapy for br...
Article
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Background In this exploratory study, the impact of local irradiation on systemic changes in stress and immune parameters was investigated in eight patients treated with intensity-modulated radiation therapy (IMRT) or stereotactic ablative body radiotherapy (SABR) for prostate adenocarcinoma to gain deeper insights into how radiotherapy (RT) modula...
Article
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Following cell stress such as ionising radiation (IR) exposure, multiple cellular pathways are activated. We recently demonstrated that ferredoxin reductase (FDXR) has a remarkable IR-induced transcriptional responsiveness in blood. Here, we provided a first comprehensive FDXR variant profile following DNA damage. First, specific quantitative real-...
Article
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Acute myeloid leukemia (AML) is an aggressive cancer that progresses rapidly with a poor prognosis. Cytogenetic analysis provides the most accurate determination of diagnosis and prognosis however, about 42-48% of AML patients have a cytogenetically normal karyotype. Genetic analysis can provide further information and the identification of new mut...
Article
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The NATO HFM 291 research task group (RTG) on "Ionizing Radiation Bioeffects and Countermeasures" represents a group of scientists from military and civilian academic and scientific institutions primarily working in the field of radiobiology. Among other tasks, the RTG intends to extend their work on risk estimation and communication to bridge the...
Article
Full-text available
In the event of a large-scale event leading to acute ionizing radiation exposure, high-throughput methods would be required to assess individual dose estimates for triage purposes. Blood-based gene expression is a broad source of biomarkers of radiation exposure which have great potential for providing rapid dose estimates for a large population. T...
Article
The 16th International Congress of Radiation Research (ICRR2019) was held in Manchester, UK, in August 2019. The Congress, which is held every four years, covered a wide spectrum of topics relevant for all aspects of radiation research including basic mechanisms, translational research, radiotherapy and health effects, and ecology. Here, we provide...
Article
Full-text available
The genes coding for the antigenic T cell receptor (TR) subunits are assembled in thymocytes from discrete V, D, and J genes by a site-specific recombination process. A tight control of this activity is required to prevent potentially detrimental recombination events. V, D, and J genes are flanked by semi-conserved nucleotide motives called recombi...
Article
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Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translate...
Article
Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translate...
Article
Full-text available
Therapy-related and more specifically radiotherapy associated acute myeloid leukaemia (AML) is a well-recognised potential complication of cytotoxic therapy for the treatment of a primary cancer. The CBA mouse model is used to study radiation leukaemogenesis mechanisms with Sfpi1/PU.1 deletion and point mutation already identified as driving events...
Article
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Though radiotherapy is a local therapy, it has systemic effects mainly influencing immune and inflammation processes. This has important consequences in the long-term prognosis and therapy individualization. Our objective was to investigate immune and inflammation-related changes in the peripheral blood of head and neck cancer patients treated with...
Article
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Purpose: The workshop on ‘Individual Radiosensitivity and Radiosusceptibility’ organized by MELODI and CONCERT on Malta in 2018, evaluated the current state of assays to identify sensitive and susceptible subgroups. The authors provide an overview on potential screening assays detecting individuals showing moderate to severe early and late radiatio...
Article
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Individual variability in response to radiation exposure is recognised and has often been reported as important in treatment planning. Despite many efforts to identify biomarkers allowing the identification of radiation sensitive patients, it is not yet possible to distinguish them with certainty before the beginning of the radiotherapy treatment....
Article
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Gene expression (GE) assays have shown great potential for rapid individual radiation dose exposure assessment. The aim of the present study was to optimise GE-based biological dosimetry protocols for radiological emergencies. Experiments were carried out to validate a newly developed protocol (P2) where several steps were optimised and to compare...
Article
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For many diseases with a foetal origin, the cause for the disease initiation remains unknown. Common childhood acute leukaemia is thought to be caused by two hits, the first in utero and the second in childhood in response to infection. The mechanism for the initial DNA damaging event are unknown. Here we have used in vitro, ex vivo and in vivo mod...
Article
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The focus of this research is to combine statistical and machine learning tools in application to a high-throughput biological data set on ionizing radiation response. The analyzed data consist of two gene expression sets obtained in studies of radiosensitive and radioresistant breast cancer patients undergoing radiotherapy. The data sets were simi...
Article
Studies of the responses of haematopoietic stem and progenitor cells (HSPCs) to low doses of ionising radiation formed an important aspect of the RISK-IR project (www.risk-ir.eu) . A brief overview of these studies is presented here. The findings confirm the sensitivity of HSPCs to radiation even at low doses, and illustrate the substantial impact...
Article
The RTGene study was focused on the development and validation of new transcriptional biomarkers for prediction of individual radiotherapy patient responses to ionizing radiation. In parallel, for validation purposes, this study incorporated conventional biomarkers of radiation exposure, including the dicentric assay. Peripheral blood samples were...
Article
Full-text available
Background: Microsatellite and chromosomal instability have been investigated in Hodgkin lymphoma (HL). Materials and Methods: We studied seven HL cell lines (five Nodular Sclerosis (NS) and two Mixed Cellularity (MC)) and patient peripheral blood lymphocytes (100 NS-HL and 23 MC-HL). Microsatellite instability (MSI) was assessed by PCR. Chromosoma...
Article
Full-text available
For triage purposes following a nuclear accident, blood-based gene expression biomarkers can provide rapid dose estimates for a large number of individuals. Ionizing-radiation-responsive genes are regulated through the DNA damage-response pathway, which includes activation of multiple transcription factors. Modulators of this pathway could potentia...
Article
Purpose: The review aims to discuss the prominence of dietary and metabolic regulators in maintaining HSC function, long-term self-renewal and differentiation. Results: Most adult stem cells are preserved in a quiescent, non-motile state in vivo which acts as a “protective state” for stem cells to reduce endogenous stress provoked by DNA replicatio...
Article
Full-text available
Epidemiological studies have demonstrated an increased leukemia incidence following ionizing radiation exposure, but to date, the target cells and underlying mechanisms of radiation leukemogenesis remain largely unidentified. We engineered a mouse model carrying a different fluorescent marker on each chromosome 2, located inside the minimum deleted...
Article
Full-text available
The increasing risk of acute large-scale radiological/nuclear exposures of population underlines the necessity of developing new, rapid and high throughput biodosimetric tools for estimation of received dose and initial triage. We aimed to compare the induction and persistence of different radiation exposure biomarkers in human peripheral blood in...
Data
Gating strategy for flow-cytometry (Annexin V) experiment. (A) Dot plot analysis shows the region of lymphocytes (R1), PBMC (R2) and granulocytes (R3) based on their forward scatter (FSC) and side scatter (SSC) characteristic. (B) Dot plot analysis of lymphocytes (R1 region) shows intact cells (Annexin V-negative, PI-negative), early apoptotic cell...
Article
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Purpose: To determine whether low dose/low dose rate radiation-induced genetic instability may result from radiation-induced inactivation of mechanisms induced by the ATM-dependent DNA damage response checkpoint. To this end, we analysed the faithfulness of T cell receptor (TR) gene rearrangement by V(D)J recombination in DNA from mice exposed to...
Article
Full-text available
Previous investigations in gene expression changes in blood after radiation exposure have highlighted its potential to provide biomarkers of exposure. Here, FDXR transcriptional changes in blood were investigated in humans undergoing a range of external radiation exposure procedures covering several orders of magnitude (cardiac fluoroscopy, diagnos...
Article
The research for high-throughput diagnostic tests for victims of radio/nuclear incidents remains ongoing. In this context, we have previously identified candidate genes that predict risk of late-occurring hematologic acute radiation syndrome (HARS) in a baboon model. The goal of the current study was to validate these genes after radiation exposure...
Article
Full-text available
Previous investigations in gene expression changes in blood after radiation exposure have highlighted its potential to provide biomarkers of exposure. Here, FDXR transcriptional changes in blood were investigated in humans undergoing a range of external radiation exposure procedures covering several orders of magnitude (cardiac fluoroscopy, diagnos...