Associate Investigator Radiation Oncology, Mass General Research Institute

Associate Professor of Radiation Oncology (Radiation Biology) Harvard Medical School

bystander effect; dithiothreitol; fibroblasts; glutathione; radiation-protective agents; radiobiology; sulfhydryl compounds As part of the Cellular & Molecular Radiation Oncology Laboratory, the Held Laboratory examines molecular mechanisms in cellular responses to localized oxidative stress.  Reactive oxidizing species (ROS) are produced by many agents used in the treatment of cancer, e.g., ionizing radiation, photodynamic therapy and some chemotherapy drugs. ROS-mediated processes also play critical roles in tumor development by initiating and participating in signaling cascades that lead to mitogenesis and tumor promotion. On the other hand, ROS are also vital to some normal physiological processes. We are involved in a program including radiation biologists, photobiologists, photochemists, biophysicists, and engineers addressing the question of how reactive oxidizing species initiate a diverse array of intracellular responses and how they initiate and propagate signaling to other cells. Using time-lapse microscopy we have extended the studies of others to show that x-ray irradiated cells can undergo apoptosis either rapidly, generally after higher doses, or at a delayed time after one or more cell divisions, usually occurring after lower radiation doses. Using caspase inhibitors and substrates we are studying the pathways involved in the pre- and post-mitotic apoptosis, and in apoptosis initiated by nuclear versus non-nuclear energy deposition.