Background
Division of Molecular and Cellular Oncology (DMCO)
The Experimental Division of the Department of Radiation Oncology will continue to create an environment of excellence and leadership in biological aspects of radiation research as it relates to radiation therapy. Basic, translational, and clinical research programs will be developed that evaluate and contribute to medical scientific knowledge in the discipline. Training Programs will continue to educate scientists, residents, and staff in radiation biology to the highest level of achievement and in how to apply their knowledge for the benefit of cancer patients and society in general.
Radiation Biology
The UCLA Radiation Biology Program has a long and distinguished history, being almost as old as the UCLA Medical Center. The current Experimental Division was, however, founded in 1980, 5 years after the development of the Department of Radiation Oncology, with Dr. Withers as the Director, a role Dr. McBride assumed in 1993. Situated primarily in the Roy E. Coats Labs in the basement of the David Geffen School for Medicine and the Factor Building, the Division has almost 6,000 square feet of well-equipped lab and office space and a defined-flora Radiation Biology specific Mouse Colony of 3,800 square feet. The faculty of Drs. McBride, Withers, Cacalano, Iwamoto, and Pajonk teach radiation biology within the Biomedical Physics Graduate Program at UCLA, as well as teaching Radiation Oncology residents. The Division harnesses multiple strengths within the Department and at UCLA to build a rich environment for research and training in radiation sciences.
Research Goal
The goal of the UCLA Radiation Biology Group is to develop novel approaches to modification of the response of tumors and normal tissues to clinically relevant doses of radiation. One concept that was developed within the Division is that radiation imposes molecular "signatures" on cells and tissues that are a response to a "sense of danger." Such responses, in concert with existing molecular pathways promote intracellular and intercellular communication leading to the multiple consequences of radiation exposure. These pathways define intrinsic cellular radiosensitivity and can be modulated rationally to improve the therapeutic benefit to be derived from clinical radiation therapy.
Four main areas of research exist within the Division
Proteasomes: We were the first to show that the proteasome is a direct redox-sensitive target for radiation and that even very low doses can slow the rate of protein degradation, including that of critically important signaling molecules. Proteasome inhibition using drugs is a useful means of causing radiosensitization in vitro and in vivo. Led by Frank Pajonk and William H. McBride.
Stem Cells: The faculty has extensive experience in stem cell research, especially in normal tissues and we were the first to describe the radiation resistance of breast cancer stem cells.Relative radioresistance in the intrinsic radiosensitivity of stem cells in normal and tumorous tissues is a likely cause of normal tissue and tumor regeneration after radiation exposure that is an intensive area of research in the lab. Led by Frank Pajonk
Growth factor and cytokine signaling: These pathways influence the response of normal tissues and tumors to irradiation. We have shown now TNFR signaling dictates the response of normal brain to irradiation. In addition, we have a large research effort in the control of these pathways through SOCS proteins and how their expression modulates radiation responses. Led by Nick Cacalano and William H. McBride.
Immunity and Radiation: The intercellular "danger" response to radiation would be expected to activate antigen presenting cells resulting in the development of immune responses. In fact, we believe that radiation is a poor signal for this response and indeed switches off antigen presentation by dendritic cells without killing them. We are involved in attempts to prevent this functional immunosuppression and so as to better translate tumor cell killing into the generation of tumor-specific immunity. This would help improve local control and eliminate micrometastatic disease. Led by William H. McBride.
