Education

B.S., Marine Science; B.S. Chemistry, Southampton College, 1975
M.S., Chemistry, Yale University, 1977
Ph.D., Chemistry, Yale University, 1981

Research Interests

Mechanisms of Normal Tissue Damage 

One of the major unresolved issues in radiation biology is whether normal tissue damage is caused by damage to the microvasculature or direct damage to the clonogenic functional cells. It has long been assumed that early effects are due to damage to the rapidly dividing stem cell populations and that late effects are due to damage to the more slowly growing blood vessels. However, several recent, and controversial, reports have suggested that microvascular damage is causative in an acute effect: the loss of intestinal crypt stem cells and the subsequent development of the gastrointestinal syndrome. We have developed a novel method for selective irradiation of the microvasculature that allows direct experimental testing of the role of the vasculature in normal tissue radiation response. A boron compound has been prepared that will remain inside the blood vessels. The short path length of the radiations from the boron neutron capture reaction allows irradiation of the blood vessel walls but not the surrounding functional cells. Initial results indicate that the acute effect in the intestine, the gastrointestinal syndrome, is NOT caused by damage to the blood vessels, but by direct damage to the stem cells in the intestinal crypts. The major impact of this technique could come from the study of late effects in normal tissues. Late normal tissue damage takes months or years to develop. Knowledge of the cell types and signaling molecules that initiate the process that leads to the development of late effects could have significant implications for the development of agents to protect normal tissues during radiation therapy or to treat normal tissues after accidental radiation exposure.

The Bystander Effect

The effects of alpha particle radiation on DNA, on cell survival, as well as on the complex biological signaling pathways that exist within and between cells are under investigation. Alpha particle sources have been developed for irradiation of cells in culture, and for studies on the bystander effect, a recently discovered phenomenon whereby non-targeted cells still experience DNA damage and death. Using a two-layer co-culture system whereby one layer of cells is exposed to the alpha particles and the second layer of cells is not irradiated, but only co-cultured in the same growth medium, we have recently demonstrated significant levels of DNA damage in the unirradiated prostate tumor cells.   This bystander effect is completely blocked by the addition of a radical scavenger into the cell culture medium. The model system will allow us to study the chemical signaling pathways involved in the bystander effect with the aim of manipulation of this pathway to increase the level of cell kill in tumor sites treated with alpha particle-labeled antibodies through synergistic effects with chemotherapy agents.

Boron Neutron Capture Therapy (BNCT)

BNCT is a binary radiation therapy that requires the selective delivery of a boron-containing drug to tumor, followed by irradiation of the entire tumor region, including surrounding normal tissues, with low-energy neutrons. The short-range radiations released from the boron-neutron interaction restrict most of the radiation damage to boron-loaded cells. The distribution of the boron-containing drug is, thus, critical to the effect and the effectiveness of BNCT. Dr. Coderre’s research quantified the radiation biology of BNCT and is the basis of several past and current clinical trials of BNCT for the treatment of brain tumors carried out at Brookhaven National Laboratory, MIT and in Europe. Research continues in the evaluation of new boron delivery agents and the effects of these compounds on tumor and normal tissues, with the aim of extending BNCT to other tumors such as lung tumors or head and neck tumors.

 

Selected Recent Publications

1. Coderre, J.A. and Morris, G.M., The radiation biology of boron neutron capture therapy. Radiation Research, 151, 1-18, 1999.
2. Coderre, J.A., Turcotte, J.C., Riley, K.J., Binns, P.J., Harling, O.K., Kiger III, W.S., Boron Neutron Capture Therapy: Cellular targeting of high linear energy transfer radiation. Technology in Cancer Research and Treatment, 2, 1-22, 2003. (invited review)
3. Barth, R.F., Coderre, J.A., Vicente, G.H., Blue, T.E. Boron neutron capture therapy of cancer: Current status and future prospects. Clinical Cancer Research, 11, 3987-4002, 2005.
4. Collins, C., Zhou, X., Wang, R., Barth, M.C., Jiang, T., Coderre, J.A., Dedon, P.C.   Differential oxidation of deoxyribose in DNA by γ- and α-radiation. Radiation Research, 163, 654-662, 2005.
5. Harling, O.K., Riley, K.J., Binns, P.J., Patel, H., Coderre, J.A. The MIT User Facility for Neutron Capture Therapy Research. Radiation Research, 164, 221-229, 2005.
6. Wang, R. and Coderre, J.A. A bystander effect in alpha particle irradiations of human prostate tumor cells. Radiation Research, 164, 711-722, 2005.
7. Schuller, B.W., Binns, P.J., Riley, K.J., Ma, L., Hawthorne, M.F., Coderre, J.A. Selective irradiation of the vascular endothelium has no effect on the survival of murine intestinal crypt stem cells. Proc. Natl. Acad. Sci., USA, 103, 3787-3792, 2006.
8. Otsuka, S., Coderre, J.A., Micca, P.L., Morris, G.M., Hopewell, J.W., Rola, R., Fike, J.R. Depletion of Neural Precursor Cells Following Local Brain Irradiation is due to Radiation Dose to the Parenchyma not the Vasculature. Radiation Research, 2006 (in press).