Dmitry Klokov

Biography

Dr. Dmitry Klokov joined the University of Ottawa as an Adjunct Professor in 2017. He has been leading the Section of Radiobiology at Canadian Nuclear Laboratories (formerly known as Atomic Energy of Canada Limited) since 2007. Dr. Klokov 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. After completing postgraduate studies at Case Western Reserve University, British Columbia Cancer Research Centre and German Cancer Research Centre (DKFZ) in radiation oncology and radiobiology, Dr. Klokov went to Chalk River, Ontario, to join then Atomic Energy of Canada Limited and to establish his group where he currently carries out his research in various fields of radiobiology.

Dr. Klokov is currently looking for one or two MSc and PhD students and one postdoctoral fellow.  Please contact Dr. Klokov. 

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 such 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, such as X-rays, gamma-rays and beta-particles (tritium). We are interested in understanding how low-dose ionizing radiation affects stability of the genome, epigenetic and other regulatory molecular networks that eventually contribute to delayed systemic health related outcomes, such as altered immune functions, functions of stem cells, carcinogenesis and aging. Our overall goal is to inform radiation protection standards that regulate occupational, medicinal or accidental exposures of humans to low doses of ionizing radiation. Additionally, we are also exploring how low-dose radiation may be used in medicine to help treat various diseases, such as cancer and muscle dystrophies.

Research Interests

Most of our studies utilize a globally unique low-dose irradiation animal facility, located at Canadian Nuclear Laboratories in Chalk River and equipped with cutting edge tools and technologies, such as an in vivo small animal imager, NGS sequencer, high-content screening system, FACS sorting and others. We use a variety of experimental models both in vitro and in vivo and pursue our goals in a number of different directions as follows.

• 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 gamma- or beta-radiation and to understand how these affect tumorigenesis in various tissues. We are currently running studies using the APC^min/+ colon cancer mouse, the MMTV-Neu breast cancer mouse and the A/J lung cancer mouse. A variety of end-points are monitored, including tumor rates and their histology, immunologic changes, DNA damage and repair, gene expression, etc.
• 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 this study, 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 immune system playing one key role.
• Immune checkpoint therapy is a novel cancer treatment modality that has become an important part of treatment of some cancer types. It makes use of patient’s own immune system to recognize and kill cancer cells. However, it has a number of limitations that are currently unresolved. Using our previous knowledge and results, we proposed that low-dose irradiation may improve therapeutic outcome of the immune checkpoint therapy. One of our current studies is aimed at testing this hypothesis using allogenic mouse xenograft studies.
• Regenerative medicine is another branch of medicine that has gained considerable attention and momentum, with several stem cell therapies approved by FDA in recent years and dozens of clinical trials in progress. This line of our research explores ways of improving current and potential future stem cell therapies by making use of some very specific effects that low-dose radiation may exert on stem cells. Our current models includes muscle, mesenchymal and hematopoietic stem cells.

We invite graduate students and postdoctoral fellows to join our vibrant team of researchers and to participate in these exciting studies at a premier research site in Canada located next to the Algonquin National Park. Those interested are encourage to send their CV to Dr. Dmitry Klokov with an indication of a project of interest.

Select Publications

• 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.
• Flegal M, Blimkie M, Wyatt H, Bugden M, Surette J, Klokov D. (2015) Measuring DNA Damage and Repair in Mouse Splenocytes After Chronic In Vivo Exposure to Very Low Doses of Beta- and Gamma-Radiation. J Vis Exp. (101): e52912.
• 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.
• Velegzhaninov IO, Shadrin DM, Pylina YI, Pystina AV, Shostal OA, Belykh ES, Kaneva AV, Ermakova OV, Klokov DY. (2015) Differential Molecular Stress Responses to Low Compared to High Doses of Ionizing Radiation in Normal Human Fibroblasts. Dose-Response. 13(1).
• Osipov A, Smetanina N, Pustovalova MV, Arkhangelskaya E, Klokov D. (2014) The formation of DNA single-strand breaks and alkali-labile sites in human blood lymphocytes exposed to 365 nm UVA radiation. Free Rad Biol Med. 73: 34-40
• Blimkie MSJ, Fung LCW, Petoukhov ES, Girard C, Klokov D. (2014) Repair of DNA double strand breaks is not modulated by low dose gamma-radiation in C57Bl/6J mice. Radiat Res. 181(5): 548-553
• Osipov AN, Buleeva G, Arkhangelskaya E, Klokov D (2013). In vivo gamma-irradiation low dose threshold for suppression of DNA double strand breaks below the spontaneous level in mouse blood and spleen cells. Mutat Res. 756: 141-145
• Klokov D, Leskov K, Araki S, Zou Y, Goetz EM, Luo X, Willson D,  Boothman DA (2013). Low dose IR-induced IGF-1-sCLU expression: a p53-repressed expression cascade that interferes with TGFbeta1 signaling to confer a pro-survival bystander effect. Oncogene. 32: 479-490.
• Banath JP, Klokov D, MacPhail SH, Banuelos CA, Olive PL (2010). Residual gammaH2AX foci as an indication of lethal DNA lesions. BMC Cancer. 10(4).
• Banath JP, Banuelos CA, Klokov D, MacPhail SM, Lansdorp PM,  Olive PL (2009). Explanation for excessive DNA single-strand breaks and endogenous repair foci in pluripotent mouse embryonic stem cells. Exp Cell Res. 315: 1505-1520.