Cancer Mechanisms and Biomarkers Group
Introduction
Protecting and improving human health is at the heart of the biological research being carried out in the Cancer Mechanisms and Biomarkers group. More specifically, we are trying to better understand the mechanisms by which acute or protracted ionising radiation exposure either of natural or medical origin interacts and affects cells and individuals.
Carcinogenesis is the process by which normal cells are transformed into cancer cells. Most cancers are probably initiated by a change in the cell's DNA sequence or an epigenetic modification. Although we know relatively well how radiation-induced DNA damage in cells occurs and the repair pathways involved, the rate-limiting step for new approaches for either preventing cancers or detecting them early is the fundamental lack of knowledge about the sequence of the earliest molecular events. One of our aims is to understand the role of these events by monitoring the progression of initiated, 'pre-cancerous' cells that acquire critical characteristics in a stepwise fashion sometimes over years after radiation exposure and this can be done in vivo.
Another related aim is to discover and validate biomarkers of radiation exposure, toxicity, long term effects and susceptibility using blood samples from healthy donors and cancer patients exposed to radiation from CT scans to radiotherapy treatments. Ultimately, this knowledge is used to support health decisions by the public and policymakers and will allow individual differences in sensitivity to be taken into account to better protect those at higher risk by regularly monitoring them, decreasing the risk and to intervene to treat cancer earlier.
Networks
National Institute for Health Research, Health Protection Research Units:
- Chemical and Radiation Threats and Hazards
- Health Impact of Environmental Hazards
- The Cancer mechanisms and biomarkers group is actively involved in the Multidisciplinary European Low Dose Initiative (MELODI) and member of the European network of biological dosimetry (RENEB, Realizing the European Network of Biodosimetry, http://reneb.eu/ ) with which we participating to exercises where we receive coded blood samples exposed to unknown doses of ionising radiation which we have to analysed and provide rapid dose estimates.
External funding
National Institute of Health Research (NIHR), the European Community seventh framework programme. Project Risk, Stem Cells and Tissue Kinetics - Ionising Radiation (RISK-IR), project VIBRATO (OPERRA), project LEU-TRACK (CONCERT), the NIAID/NIH Centers for Medical Counter Measures Against Radiation Consortium (CMCRC) Program, the US department of Energy, the EMF trust and UK Department of Health.
Meet the Group
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Christophe identified the first radiotherapy patient whose radiation toxicity was due to a defect in DNA DSB repair which was thought to be almost incompatible with survival at the time; it was found later that the patient had a mutation in ligase IV. After several post-doctorate positions, Christophe became in 2005 the head of the Cancer Mechanisms and Biomarkers group in the Radiation Effects department.
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Lourdes Cruz-Garcia started her research career at the University of Barcelona (Spain) where she received her MSc and PhD. After her postdoctoral studies at the department of human genetics at the University of Utah (USA), she was recruited at UKHSA's RCE in Cancer Mechanisms and Biomarkers group. Currently, she is co-leading the group with Dr Christophe Badie.
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Paul is a Principal Radiation Protection Scientist in the Cancer Mechanisms and Biomarkers group of the Radiation Effects Department at United Kingdom Health Security Agency Radiation, Chemical and Environmental Hazards (RCE). Paul has worked at NRPB/HPA/PHE/UKHSA since 1982.
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Rosemary is a Principal Radiation Protection Scientist with more than 25 years of experience working in the Radiation Effects department of UKHSA's Chemical, Radiation and Environmental Hazards. Rosemary's main research area is the chromosomal and molecular mechanisms that underlie radiation-induced leukaemia initiation and development, and she has co-authored 20 peer-reviewed publications in this field.
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Grainne obtained her PhD from Brunel University (UK) where she focused on investigating the genetic and epigenetic pathways affected in the development of acute myeloid leukaemia after radiation exposure. Grainne has been involved in numerous RENEB European exercises using our gene expression assay to provide rapid dose estimates
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Antonella completed her undergraduate and masters at the University of Leicester, focussing on biochemistry and cancer studies. With her PhD looking at the way in which senescence can affect radiosensitivity in NSCLC patients, also at the University of Leicester, began her interest in the field of radiation effects.
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Mustafa Najim joined the Cancer Mechanisms and Biomarkers group at UKHSA in 2022. He has completed his MSc in infection and immunity at University College London (UCL).
After his graduation, he worked as an Associate practitioner for the NHS during the Coronavirus pandemic in Bracknell Hospital.
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Yannick obtained his Ph. D. at the University of Nice Sophia-Antipolis (France) working on a project on a new mechanism of regulation of potassium channels by the phospholipase D2 and the ethanol. During his Ph.D., he developed skills in cell culture and molecular biology. Following his thesis, he carried out his first postdoc at the University of Nice (France) where he studied the effects of irradiation treatment on medulloblastoma cells and highlighted the impact of lymphangiogenic factors on medulloblastoma cancer aggressiveness after an irradiation.
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Maria Polozova is a biomedical scientist with a medical degree specialising in Clinical Immunology. In 2018, as a Scientific Officer at the Grigoriev Institute for Medical Radiology and Oncology, Ukraine, she contributed to research on immunoneuroendocrine disorders in endometrial and breast cancer patients undergoing surgery and radiation therapy.
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Stan Polozov is a biomedical scientist with a specialisation in molecular biology and bioinformatics, particularly within the realms of human transcriptomics and epitranscriptomics. Having earned his MD in clinical oncology, Stan Polozov transitioned to a more research-focused career, starting with his initial collaboration and fellowship at Public Health England in 2017.
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Philip is a senior bioinformatician working in the Cancer Mechanisms and Biomarkers group within UKHSA's Chemical, Radiation and Environmental Hazards. He is involved in several research projects aimed at better understanding the effects of medical, occupational and accidental exposure of ionising radiation on human health.
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Milagrosa López Riego has been a member of the Cancer Mechanisms and Biomarkers Group (Radiation Effects Department, UKHSA) since November 2023, after completing her PhD studies on biomarkers of ionizing radiation (IR) relevant to carcinogenesis at Stockholm University (Sweden). During her PhD studies, Milagrosa developed a strong interest in radiation protection.
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Areas for potential collaboration
We are continuously seeking potential collaborations with all research establishments (universities, institutes and government organisations) to study the effects of environmental agents on brain functions, epigenetics, and behaviour.
Contact us
Contact us if you would like to find out more detail or stay informed about a particular field of research. We are always interested in collaborating and are open to partnerships, to drive forward innovation for the benefit of the public.
Publications
Last four years publications
- Brown N, Finnon R, Finnon R, McCarron R, Cruz-Garcia L, O'Brien G, Herbert E, Scudamore CL, Morel E and Christophe Badie. Hemizygous R235C Spi1 point mutation confers hypersensitivity to ionising radiation-induced Acute Myeloid Leukaemia (AML) iScience 2023
- Polozov S, Cruz-Garcia L, O'Brien G, Goriacha V, Nasser F, Jeggo P, et al. Deficient radiation transcription response in COVID-19 patients. Advances in Radiation Oncology. 2023:101215.
- Cruz-Garcia L, Nasser F, O'Brien G, Grepl J, Vinnikov V, Starenkiy V, et al. Transcriptional Dynamics of DNA Damage Responsive Genes in Circulating Leukocytes during Radiotherapy. Cancers. 2022;14(11):2649.
- Karabulutoglu M, Finnon R, Cruz-Garcia L, Hill MA, Badie C. Oxidative Stress and X-ray Exposure Levels-Dependent Survival and Metabolic Changes in Murine HSPCs. Antioxidants. 2022;11(1):11.
- Cruz-Garcia L, Badie C, Anbalagan S, et al. An ionising radiation-induced specific transcriptional signature of inflammation-associated genes in whole blood from radiotherapy patients: A pilot study. Radiat Oncol 2021;16:83.
- Nasser F, Cruz-Garcia L, O'Brien G, et al. Role of blood derived cell fractions, temperature and sample transport on gene expression-based biological dosimetry. Int J Radiat Biol 2021;97:675-686.
- Cruz-Garcia L, O'Brien G, Sipos B, et al. In vivo validation of alternative fdxr transcripts in human blood in response to ionizing radiation. International Journal of Molecular Sciences 2020b;21.
- Cruz-Garcia, L., O'Brien, G., Sipos, B., Mayes, S., Love, M.I., Turner, D.J., and Badie, C. Generation of a transcriptional radiation exposure signature in human blood using long-read nanopore sequencing. Radiation Research (2020a).
- Frey B, Mika J, Jelonek K, Cruz-Garcia L, Roelants C, Testard I, et al. Systemic modulation of stress and immune parameters in patients treated for prostate adenocarcinoma by intensity-modulated radiation therapy or stereotactic ablative body radiotherapy. Strahlenther Onkol. 2020.
- O'Brien, G., Cruz-Garcia, L., Zyla, J., Brown, N., Finnon, R., Polanska, J. and Badie, C. Kras mutations and PU.1 promoter methylation are new pathways in murine radiation-induced AML. Carcinogenesis (2019).
- Balázs, K., Kis, E., Badie, C., Bogdándi, E. N., Candéias, S., Cruz Garcia, L., Dominczyk, I., Frey, B., Gaipl, U., Jurányi, Z. et al. Radiotherapy-Induced Changes in the Systemic Immune and Inflammation Parameters of Head and Neck Cancer Patients. 11(9), 1324 (2019).
- Polozov S, Cruz-Garcia L, Badie C. RAPID GENE EXPRESSION BASED DOSE ESTIMATION FOR RADIOLOGICAL EMERGENCIES. Radiat Prot Dosimetry. 2019 Apr 23. pii: ncz053.
- Mansell E, Zareian N, Malouf C, Kapeni C, Brown N, Badie C, Baird D, Lane J, Ottersbach K, Blair A, Case CP. DNA damage signalling from the placenta to foetal blood as a potential mechanism for childhood leukaemia initiation. Sci Rep. 2019 Mar 13;9(1):4370.
- Zyla J, Kabacik S, O'Brien G, Wakil S, Al-Harbi N, Kaprio J, Badie C, Polanska J, Alsbeih G. Combining CDKN1A gene expression and genome-wide SNPs in a twin cohort to gain insight into the heritability of individual radiosensitivity. Funct Integr Genomics. 2019 Jan 31.
- Gault N, Verbiest T, Badie C, Romeo PH, Bouffler S.Hematopoietic stem and progenitor cell responses to low radiation doses-implications for leukemia risk. Int J Radiat Biol.2019 Jan 17:1-8.