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Department of Space Radiobiology
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Update time: 2012-12-25
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The main task of the Department of Space Radiobiology is to establish accurate risk assessment models of space radiation and develop efficient countermeasures for the long-term manned deep space exploration. Our research focus areas include epigenetic changes, genomic instability, cell transformation and accelerated senescence induced by heavy ion radiation. Intercellular communication, protection countermeasures and the combined effects of cosmic rays and other stresses in space are being planned.

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1. Achievements

1.1 Radiation-related microRNAs

MicroRNA (miRNA), a class of small non-coding RNAs, regulates the expression of its target genes by inducing miRNA degradation or repressing translation through binding to the 3’-UTR of its target genes. More and more evidences show that miRNAs are involved in radiation-induced cellular responses. Basing on our hypothesis that some miRNAs expressed at low abundance under normal condition might be up-regulated and become detectable after exposure to ionizing radiation, we identified ten novel miRNAs induced by X-ray radiation.

We also found that miR-185 expression was reduced in renal carcinoma tissues and cell lines exposed to ionizing radiation and verified that miR-185 mediated cell radio-sensitivity by directly targeting ATR, one of the most important DNA damage sensors and transducers. This finding shed lights on the potential applications for miR-185 in therapeutic intervention and radio-sensitization. Furthermore, we identified that miR-3928 was implicated in cellular response to ionizing radiation by repressing the expression of Dicer, a key component of the miRNA processing machinery, which might be an explanation of the radiation-induced depression of miR-185.

1.2 Lethal Effects of Heavy Ions on Cancer Stem Cell

Comparing with conventional radiotherapy, heavy ion tumor treatment has achieved excellent outcome with very low recurrence rate. Thus we supposed that heavy ion radiation causes lethal damages to cancer stem cells (CSCs). To prove this hypothesis, we exposed two in vitro cultured human glioma cell lines, M059K with proficient DNA-PKcs and M059J with deficient DNA-PKcs, to carbon ions or X-rays. We found that CD133+ cells, which represent glioma CSCs, conferred the radio-resistance of glioma and might be the source of recurrence after conventional radiotherapy. Carbon ions demonstrated a great potential to effectively target radio-resistant CSCs, which is considered to be one of the major contributors to the high curability and low recurrence of heavy ion tumor therapy.

1.3 Others

Radiation-induced Cell Cycle Arrest Cell cycle checkpoint is a self-protective mechanism for cells to monitor genome integrity and ensure the high-fidelity transmission of genetic information to daughter cells. Insufficient function of cell cycle checkpoints has been demonstrated to partially account for tumor initiation, promotion and progression. We observed that long-term G2 cell cycle arrested cells induced by ionizing radiation in melanoma cell line 92-1 underwent accelerated senescence accompanying the degradation of Cyclin B1, AurorA and PIk1.

Radiation Protection Ionizing radiation produces reactive oxygen species (ROS) which cause damages to cells. We synthesized a class of ROS scavengers called GANRA, which were low toxic but had high radio-protective effects against both heavy ions and X-rays. Animal tests demonstrated that pre-administration of GANRA reduced tissue damage and increased the survival of mice irradiated with ionizing radiation, implying that GANRA is potentially applicable in radiation protection.

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2. Research Platforms

Affiliated to the Heavy Ion Research Facility in Lanzhou – Cooling Storage Ring (HIRFL-CSR), the only ideal accelerator in China currently available for simulating heavy ion radiation in space, two space radiation platforms have been established to meet the demand for studies on the risk assessments and countermeasures. One is high-LET platform, in which the highest LET of the beams reaches to thousands keV/µm whereas the highest energy is 100 MeV/u, and the other is high-energy platform, which provides all kinds of heavy ions with the highest energy of 1 GeV/u for iron. Animal lab and other biological labs are located near the platforms. Experiments with carbon, nitrogen, oxygen, and argon beams have been conducted on the platforms during the past decades.

The present research is focused on the designing of a multifunctional device to simulate space environment. As shown in the following figure, the typical space environment factors such as heavy ion radiation, microgravity, magnetic system, circadian rhythm and airborne particulate matter are able to be simulated. Synergistic effects caused by these multiple factors will be the next target of our research.

The multifunctional device of space environment simulated on ground

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3. Team

The research team includes 14 staff members, two visiting professors from Lanzhou University and the University of Medicine and Dentistry of New Jersey, respectively. Contact details of our stuff members are listed in the following table.

Stuff Members

Title and position

Phone

Email

Guangming Zhou

Prof. Leader

0931-4969164

zhougm@impcas.ac.cn

Jufang Wang

Prof.

0931-4969164

jufangwang@impcas.ac.cn

Burong Hu

Prof.

0931-4969169

hubr@impcas.ac.cn

Nan Ding

Assistant Research Scientist

0931-4969164

dn@impcas.ac.cn

Zhenxin Ren

Assistant Research Scientist

0931-4969146

zhxren@impcas.ac.cn

Jiayun Zhu

Assistant Research Scientist

0931-4969146

zhujiayun@impcas.ac.cn

Jinpeng He

ResearchAssistant

0931-4969164

hejp@impcas.ac.cn

Yanan Zhang

ResearchAssistant

0931-4969164

zhangyanan@impcas.ac.cn

Tingting Liu

ResearchAssistant

0931-4969739

emily0711@impcas.ac.cn

Dan Xu

ResearchAssistant

0931-4969739

xudan@impcas.ac.cn

Junrui Hua

ResearchAssistant

0931-4969168

huajunrui@impcas.ac.cn

He Li

ResearchAssistant

0931-4969739

lihe2007@impcas.ac.cn

Yarong Du

ResearchAssistant

0931-4969146

duyrlive@hotmail.com

Yaxiong Chen

ResearchAssistant

0931-4969146

chenyx07@impcas.ac.cn

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4. Recent Publications

1) Lei Chang, Wentao Hu, Caiyong Ye, Bin Yao, Lei Song, Xin Wu, Nan Ding, Jufang Wang and Guangming Zhou. miR-3928 Activates ATR Pathway by Targeting Dicer.RNA Biology. 2012, 9(10), 1247-1254

2) Burong Hu, Peter Grabham, Jing Nie, Adayabalam S. Balajee, Hongning Zhou, Tom K. Hei and Charles R. Geard. Intrachromosomal Changes and Genomic Instability in Site-Specific Microbeam-Irradiated and Bystander Human-Hamster Hybrid Cells. Radiation Research, 2012(1), 177: 25-34

3) Jinpeng He, Junhong Li, Libin Zhou, Jiayun Zhu, Jufang Wang, AtsushiMizota, YoshiyaFurusawa, Guangming Zhou.Cell Cycle Suspension: a Novel Process Lurking in G2 Arrest. Cell cycle, 2011, 10(9): 1468-1476

4) Jiayun Zhu, Wentao Hu, Nan Ding, Caiyong Ye, MojisolaUsikalu, Sha Li, Burong Hu, Betsy M. Sutherland, Guangming Zhou.An optimized colony forming assay for low-dose-radiation cell survival measurement.Int. Res. J. Biotechnol. 2011, 2(8): 164-172 

5)Nan DING,Xin WU, Jinpeng HE, Lei CHANG, Wentao HU, Wenjian LI, Jufang WANG, Guangming ZHOU.Detection of novel human miRNAs responding to X-ray irradiation.Journal of Radiation Research. 2011, 52: 425-432

6)Jufang Wang, Fengtao Su, Lubomir B. Smilenov, Libin Zhou, Wentao Hu, Nan Ding and Guangming Zhou. Mechanisms of increased risk of tumorigenesis in Atm and Brca1 double heterozygosity. Radiation Oncology. 2011, 6:96-104

7)Guangming Zhou, Lubomir B Smilenov, Howard B Lieberman, Thomas Ludwig, Eric J Hall. Radiosensitivity to high energy iron ions is influenced by heterozygosity for ATM, RAD9 and BRCA1. Advances in Space Research.2010, 46: 681-686

8) Fengtao Su, Lubomir B Smilenov, Thomas Ludwig, Libin Zhou, Jiayun Zhu, Guangming Zhou and Eric J Hall.Hemizygosity for Atm and Brca1 influence the balance between cell transformation and apoptosis. Radiation Oncology.2010, 5:15

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