Dmitry Klokov

Biography

Short Bio

Dr. Dmitry Klokov joined the University of Ottawa as an Adjunct Professor in 2017. He is currently carrying out his research in various fields of low-dose radiobiology as a head of the Laboratory of Experimental Radiobiology and Radiotoxicology at the French Institute of Radioprotection and Nuclear Safety (IRSN) in Paris, France. Prior to that, Dr. Klokov was with the Canadian Nuclear Laboratories (CNL) where he spent 12 years establishing and leading the CNL low-dose radiobiology research program. He accomplished his undergraduate and graduate studies in Russia where he obtained a BSc from Krasnoyarsk State University, an MSc from Pushchino State University and then a PhD from Moscow State University. Dr. Klokov’s post-graduate studies were at Case Western Reserve University (USA), British Columbia Cancer Research Centre (Canada) and German Cancer Research Centre in Radiation Oncology and Radiobiology.

Background for Research Interests

Are CT scans safe? Is living near nuclear plants safe? These are examples of generic societally important questions that remain unanswered. We convert these questions into scientific questions/hypothesis and test them in our laboratory using state-of-the-art science and technology.

Our research mainly concerns low doses of ionizing radiation from both external (e.g. X-rays and gamma-rays) and internal (e.g. radiation emitted from tritium, uranium and cesium) sources. We are interested in understanding how low-dose ionizing radiation affects stability of the genome, epigenetic and other regulatory molecular networks and how they drive tissue and immune system alterations that eventually contribute to adverse health outcomes, such as cancer, brain or cardiovascular pathologies. Our overall goal is to inform radiation protection standards that regulate occupational, medical or environmental exposures of humans to low doses of ionizing radiation.

Research Interests

Most of our studies utilize globally unique low-dose irradiation animal facilities, located at the Institute of Radioprotection and Nuclear Safety in Paris, France and at the Canadian Nuclear Laboratories in Chalk River, Canada. Equipped with cutting-edge tools and technologies and supported by experienced researchers and technologists, as well as by a global network of collaborators, we use a variety of experimental models both in vitro and in vivo to pursue our goals in several different directions:

• Cancer: in our in vivo cancer studies, we use mouse cancer models to examine molecular, tissue and systemic changes produced by exposure to low doses of external gamma- or internal beta-radiation from ingested tritium. We aim to understand how these changes affect tumorigenesis. We are currently running studies using the APC^min/+ colon cancer mouse. We apply Systems Biology methods, including artificial intelligence and machine learning, to get an insight into causal relationships between endpoints at various levels of biological organization: epigenome, transcriptome, DNA damage and repair, immunological, tumorigenesis and tissue pathology. We hope to contribute this new knowledge to developing an Adverse Outcome Pathway (AOP) to this or other cancer types.
• Neurobiology: using a Small Animal Radiation Research Platform, we mimic human brain exposures to low-to-intermediate radiation doses in mice and monitor neurological changes that are relevant to developing brains in children and may impact cognitive and behavioral functions. Using our unique radioactive aerosol exposure facility, we also study how inhalation of micro- and nanoparticles, e.g. tungsten particles, may result in a direct transfer of such particles to the brain via the olfactory nerve and cause neurological alterations.  
• Aging: to explore how low-dose radiation affects aging and associated aging markers, such as senescence and gene expression profiles, we use mouse models as well as cell culture in vitro models. In these studies, we consider cancer as an age-related systemic disease and therefore examine how aging and cancer may have overlapping mechanisms responsive to radiation exposures, with the regulation of translation playing one key role.
• Cardiovascular: cardiovascular changes triggered by chronic exposure to internal low-dose radiation alone or in combination with a co-stressor are studied in mouse models of atherosclerosis (ApoE^-/- mice), Marfan disease and aneurism (mgR/mgR). Alterations spanning multiple levels of biological organization are monitored with the overarching goal to reveal driving mechanisms, including immunological and inflammatory changes. We also examine how molecular changes in the heart tissue triggered by external or internal low-dose irradiation may lead to alterations in the physiological cardiac function in the long-term.
• Transgenerational: effects of low-dose radiation will be examined in a mouse model of prenatal exposure to ingested Cs-137. This study will utilize wild type mice to examine various endpoints related to genetic, epigenetic, metabolic and reproductive alterations in F1 progeny. This long-term study is thought to eventually continue by exploring multi-generational effects in F2 and F3 generations of mice.

Select Publications

• Velegzhaninov IO, Belykh ES, Rasova EE, Pylina YI, Shadrin DM, Klokov DY. (2020) Radioresistance, DNA Damage and DNA Repair in Cells With Moderate Overexpression of RPA1. Front Genet 11:855.
• Kabilan U, Graber TE, Alain T, Klokov D. (2020) Ionizing Radiation and Translation Control: A Link to Radiation Hormesis? International Journal of Molecular Sciences 21(18).
• Velegzhaninov IO, Ermakova AV, Klokov DY. (2018) Low dose ionizing irradiation suppresses cellular senescence in normal human fibroblasts. International Journal of Radiation Biology 94(9):825-828.
• Roch-Lefevre S, Gregoire E, Martin-Bodiot C, Flegal M, Freneau A, Blimkie M, Bannister L, Wyatt H, Barquinero JF, Roy L, Benadjaoud M, Priest N, Jourdain JR and Klokov D. (2018) Cytogenetic damage analysis in mice chronically exposed to low-dose internal tritium beta-particle radiation. Oncotarget 9(44):27397-27411.
• Gueguen Y, Priest ND, Dublineau I, Bannister L, Benderitter M, Durand C, Ebrahimian TG, Gregoire E, Grison S, Ibanez C,… and Klokov D. (2018) In vivo animal studies help achieve international consensus on standards and guidelines for health risk estimates for chronic exposure to low levels of tritium in drinking water. Environmental and Molecular Mutagenesis 59(7):586-594.
• Cortese F, Klokov D, Osipov A, Stefaniak J, Moskalev A, Schastnaya J, Cantor C, Aliper A, Mamoshina P, Ushakov I and others. (2018) Vive la radioresistance!: converging research in radiobiology and biogerontology to enhance human radioresistance for deep space exploration and colonization. Oncotarget 9(18):14692-14722.
• Tsvetkova A, Ozerov IV, Pustovalova M, Grekhova A, Eremin P, Vorobyova N, Eremin I, Pulin A, Zorin V, Kopnin P, Leonov S, Zhavoronkov A, Klokov D, Osipov AN. (2017) gH2AX, 53BP1, and Rad51 protein foci changes in mesenchymal stem cells during prolonged X-ray irradiation. Oncotarget. 8:64317-64329
• Zorin V, Zorina A, Smetanina N, Kopnin P, Ozerov IV, Leonov S, Isaev A, Klokov D, Osipov AN. (2017) Diffuse colonies of human skin fibroblasts in relation to cellular senescence and proliferation. Aging. 9(5):1404-1413
• Priest N, Blimkie M, Wyatt H, Bugden M, Bannister L, Gueguen Y, Jourdain J-R, Klokov D. (2017) Tritium (3H) retention in mice: administered as either HTO, DTO or as 3H-labelled amino acids. Health Phys J. 112(5):439-444
• Pustovalova M, Grekhova A, Astrelina T, Nikitina V, Dobrovolskaya E, Suchkova Y, Kobzeva I, Usupzanova D, Vorobyova N, Samoylov A, Bushmanov A, Ozerov I, Zhavoronkov A, Leonov S, Klokov D, Osipov A. (2016) Accumulation of Spontaneous gammaH2AX Foci in Long-Term Cultured Mesenchymal Stromal Cells. Aging. 8(12):3498-3506
• Bannister LA, Mantha RR, Devantier Y, Petoukhov ES, Brideau CL, Serran ML, Klokov D. (2016) Dose and Radioadaptive Response Analysis of Micronucleus Induction in Mouse Bone Marrow. Int J Mol Sci. 17(9).
• Tarrade S, Bhardwaj T, Flegal M, Bertrand L, Velegzhaninov I, Moskalev M, Klokov D (2015) Histone H2AX Is Involved in FoxO3a-Mediated Transcriptional Responses to Ionizing Radiation to Maintain Genome Stability. Int J Mol Sci. 16(12): 29996-30014.
• Osipov A, Grekhova A, Pustovalova M, Ozerov I, Eremin P, Vorobyeva N, Lazareva N, Pulin A, Zhavoronkov A, Roumiantsev S, Klokov D, Eremin I. (2015) Activation of homologous recombination DNA repair in human skin fibroblasts continuously exposed to low dose-rate X-ray radiation. Oncotarget. 6(29): 26876-85.
• Osipov A, Grekhova A, Pustovalova M, Grekhova A, Eremin P, Vorobyeva N, Pulin A, Zhavoronkov A, Roumiantsev S, Klokov D, Eremin I. (2015) Low doses of X-rays induce prolonged and ATM-independent retention of γH2AX foci in human gingival mesenchymal stem cells. Oncotarget. 6(29): 27275-87.