Michael C. Joiner

Michael C. Joiner, Ph.D.

4100 John R.
Detroit, MI 48201

Research Description:
Our overarching mission is to explore the biological basis for radiotherapy in order to develop strategies for overcoming its limitations and to better understand the biology and treatment of cancer in general. A key issue is to identify the molecular basis for radiation resistance and sensitivity, so that appropriately intense radiotherapy can be prescribed to patients which will control their cancer without excessive normal tissue complications. As part of this goal, we have discovered that cells respond hypersensitively to very small doses of radiation in a number of malignant cell lines, particularly those which are resistant to the higher dose fractions used in conventional radiotherapy. Evidence implicates reduced DNA repair following the smaller doses and our work aims to understand the molecular basis for this. A particular focus is on regulation of double-strand break repair by cell-cycle checkpoints. We have found that cells have a threshold for detection of DNA damage which corresponds to radiation doses of about one tenth those given in daily radiotherapy. Below this dose, cells fail to recognize damage and initiate cell division which causes death. Above this threshold dose, damage is detected by the ATM protein which activates downstream cell cycle checkpoints which allow DNA repair to take place which in turn increases the probability of the cell surviving. We expect to translate these observations at the cellular level into more effective therapy for resistant tumors. Another facet of hypersensitivity to low radiation doses, is that environmental exposures, or those low exposures received received outside the target volume in radiotherapy, might cause excess incidence of cancer compared with higher doses. We are studying this issue by evaluating cytogenetic changes in response to small radiation exposures.

Selected Publications:

Seth I, Schwartz JL, Stewart RD, Emery R, Joiner MC, Tucker JD. Neutron exposures in human cells: bystander effect and relative biological effectiveness. PLoS One. 2014;9:e98947.

Hillman GG, Lonardo F, Hoogstra DJ, Rakowski J, Yunker CK, Joiner MC, Dyson G, Gadgeel S, Singh-Gupta V. Axitinib Improves Radiotherapy in Murine Xenograft Lung Tumors. Transl Oncol. 2014:S1936-5233-00037-0.

Bakhmutsky MV, Joiner MC, Jones TB, Tucker JD. Differences in cytogenetic sensitivity to ionizing radiation in newborns and adults. Radiat Res. 2014;181:605-16.

Tucker JD, Joiner MC, Thomas RA, Grever WE, Bakhmutsky MV, Chinkhota CN, Smolinski JM, Divine GW, Auner GW. Accurate gene expression-based biodosimetry using a minimal set of human gene transcripts. Int J Radiat Oncol Biol Phys. 2014;88:933-9.

Tucker JD, Divine GW, Grever WE, Thomas RA, Joiner MC, Smolinski JM, Auner GW. Gene expression-based dosimetry by dose and time in mice following acute radiation exposure. PLoS One. 2013;8(:e83390.

Hillman GG, Singh-Gupta V, Lonardo F, Hoogstra DJ, Abernathy LM, Yunker CK, Rothstein SE, Rakowski J, Sarkar FH, Gadgeel S, Konski AA, Joiner MC. Radioprotection of lung tissue by soy isoflavones. J Thorac Oncol. 2013;8:1356-64.

Hillman GG, Singh-Gupta V, Hoogstra DJ, Abernathy L, Rakowski J, Yunker CK, Rothstein SE, Sarkar FH, Gadgeel S, Konski AA, Lonardo F, Joiner MC. Differential effect of soy isoflavones in enhancing high intensity radiotherapy and protecting lung tissue in a pre-clinical model of lung carcinoma. Radiother Oncol. 2013;109:117-25

Tucker JD, Vadapalli M, Joiner MC, Ceppi M, Fenech M, Bonassi S. Estimating the lowest detectable dose of ionizing radiation by the cytokinesis-block micronucleus assay. Radiat Res. 2013;180:284-91.

Cheong HS, Seth I, Joiner MC, Tucker JD. Relationships among micronuclei, nucleoplasmic bridges and nuclear buds within individual cells in the cytokinesis-block micronucleus assay. Mutagenesis. 2013;28:433-40.

Ph.D. (1980), University of London, England

Cancer Biology Courses Taught:
CB7210 Fundamentals of Cancer Biology
CB7220 Molecular Biology of Cancer Development
CB7300 Special Topics Basic Clinical Radiobiology (Course Director)
CB7240 Principles of Cancer Therapy