Basic science research at UCI Radiation Oncology involves laboratory work that addresses the genome, cells, and biology of cancers, as well as the surrounding tissues, which can impact the nature of the cancer and its potential to spread. Basic science focuses understanding of the mechanisms and causes of cancer at a biological and molecular level. Additionally, studies trying to optimize the relationship between radiation and chemotherapy and/or immunotherapy in pre-clinical models are critical to advance the field. While new knowledge may not be immediately translatable to new treatments and cures, over time the fundamental discoveries of basic science provide the foundation for better treatments and cures.
Currently, the Department has five Ph.D. radiobiologists in addition to a growing ancillary team to support clinical and translational efforts. Approximately 3,000 square feet of laboratory space is available and supports ongoing research in various areas, including stem cell biology, ultra-rapid radiation therapy delivery, immunotherapy, oligometastatic disease, and radiation-induced brain injury, among others. The Department houses a small animal irradiator, a biospecimen repository, and has access to core resources as an integral part of the NCI-designated, UCI Irvine Chao Family Comprehensive Cancer Center. Particular areas of focus include the following:
FLASH radiotherapy involves delivering radiation therapy in the blink of an eye! Laboratory studies have shown that ultra-high dose rate (> 100 Gy per second) FLASH radiation kills tumor cells similarly to conventional radiation. Unlike conventional radiation therapy, FLASH spares significantly more normal tissue, which translates to fewer side effects. UCI is at the forefront of FLASH research and is home to some of the most prominent FLASH radiobiologists in the world. In collaboration with others, UCI investigators have noted higher preservation rates of normal brain architecture after FLASH radiation compared to conventional dose (~0.01 Gy/s) rates. Much of our work is designed to characterize the oxidative changes that occur after FLASH radiation and elucidate its radioprotectant mechanism on normal tissue.
UCI Radiation Oncology is also investigating radiation- and chemotherapy-induced normal tissue injury in the brain and how stem cells can reduce its severity. Their work has defined the mechanisms underlying chemotherapy-induced cognitive decrements; a condition commonly referred to as “chemo-brain.” Their research also encompasses explaining the molecular and biochemical mechanisms regulating stem cells’ response within the irradiated microenvironment. Their goal is to discover new stem cell interventions for improving long-term mental health following cytotoxic cancer treatments.
Cognitive Pathways and Repair
Various mouse models have been developed by UCI Radiation Oncology to better understand how the molecular and cellular effects of glial cell signaling during cancer therapy can regulate brain injury. This research has helped characterize the long-term injuries to the frontal cortex and hippocampus from radiation-induced inflammation. Studies aiming to understand how repair is conducted will allow investigators to develop potential therapies in the future.
Extracellular vesicles are lipid bound vesicles secreted by cells into the extracellular space. The three main subtypes are micro-vesicles, exosomes, and apoptotic bodies, which are differentiated based upon their biogenesis, release pathways, size, content, and function. How extracellular vesicles mediate radiation response are being actively studied, as they provide a potential target for utility in cancer diagnosis and treatment.
Laboratory work focusing on the effect of radiation on the brain, specifically particle radiation encountered in space is another active area of research. Our investigators are examining the mechanisms after radiation that result in altered neuronal architecture and functionality. Utilizing a mouse model, they found that radiation to the brain impairs nerve cells from properly growing and branching, which can result in decreased memory and anxiety.
Our laboratories are actively testing natural agents in clinical use or development as radioprotectants to understand the biochemical pathways behind radiation-induced normal tissue injury. In addition, research on the efficacy of stem cell transplantation into the brain can reverse the effects of radiation-induced brain injury.