There has been an explosion of discoveries in stress signal transduction, DNA damage repair, cellular senescence, and cell-cycle checkpoints in recent years; in many cases ionizing radiation has been used as the model agent in such studies. This has led to the elucidation of a variety of promising molecular targets in fields such as cancer therapeutics. Improved instrumentation and better molecular understanding of radiation responses have both contributed to continuing advances in modern radiation oncology. This is a time of opportunity and challenge in radiation science. Development of the radiobiology program provides an important asset for the Department of Radiation Oncology, the oncology program and School of Medicine in regards to these challenges and opportunities.
Our goal is to improve our understanding of the molecular mechanisms involved in the cellular response to ionizing radiation and cancer therapy and translate our findings to develop more efficient cancer therapy. Our plan for the radiobiology program is to focus on two general areas of research and training, which are the development of modern programs in radiobiology and molecular oncology.
To conduct basic and translational research to elucidate the molecular mechanisms underlying cellular responses to ionizing radiation and chemotherapy focusing on critical cellular responses that include DNA repair, cellular senescence, cell proliferation cell death and inflammation. To understand mechanisms of tumor resistance to radiation and chemotherapy and translate our findings to develop more efficient treatment of cancer patients.
To provide high quality education and instruction in molecular radiation biology and molecular oncology to graduate and medical students, residents and postdoctoral fellows.
Thematic Areas for Consideration
A major theme for the radiobiology section is the use of radiation as a model agent to study cellular responses including genomic instability, cell cycle controls, DNA damage processing, oxidative stress, senescence, and apoptosis, as well as the signaling mechanisms mediating these and other stress responses.
- Signal transduction: From a cancer biology and cancer therapeutics standpoint, there is growing realization that the molecular responses to radiation and other cancer therapeutic agents overlap considerably with the aberrant oncogene signaling, so-called oncogenic stress. Thus, the focus of radiobiology in molecular signal transduction is directly relevant to cancer biology and cancer therapeutics. We will develop modern molecular approaches to study radiation and stress responses, and the signaling mechanisms mediating these responses.
- Tumor metabolism: Apart from numerous genetic and epigenetic lesions, deregulated metabolism has also been shown to be of great importance in the development of cancer. There is increasing evidence indicating that oncogenes and tumor suppressor genes are directly involved in the regulation of cell metabolism, which contributes to the critical alteration of multiple cellular processes and response to radio- and chemotherapy. We’ll develop a tumor metabolism program as one of the focuses of molecular oncology to investigate how deregulated metabolism can result in changes including the acquisition of cell-autonomous growth and proliferation, resistance to cancer therapy, and immortalization.
- Tumor microenvironment: The importance of the tissue microenvironment in the development of cancer, and cancer therapeutics has increasingly attracted interests of cancer biologists in recent years. We’ll develop a program to dissect the role for the tissue microenvironment in the modulation of the responsiveness of cancer cells to therapy and its correlation with inflammation, metabolism, aging, and tumorigenesis.
- Cancer stem cells: Ample evidence indicates cancer stem cells as the major source of the resistance to cancer therapy as cancer stem cells have a number of properties permitting them to survive traditional cancer chemotherapy and radiation therapy. In the hope of developing combined cancer therapy approaches targeting the cancer stem cells and the non-stem cells to improve therapeutic efficacy, we’ll develop a program to gain a better understanding of cancer stem cell biology.
- Translational research: In parallel to above proposed research focuses, we will develop complementary preclinical model systems to document the functional relevance of the various changes, develop strategies to translate these findings into new methods for improving cancer therapy.
A comprehensive program in molecular radiobiology should have a broader scope also encompassing radiation oncology and experimental cancer therapeutics, in addition to a major training mandate. Resources elsewhere in the university have the capability to extend to additional areas. Considering the potential broad scope of such a program and the current available resources, interaction and cooperation with other experts in the Greehey Children’s Cancer Research Institute, the Sam and Ann Barshop Institute for Longevity and Aging Studies, the Institute of Biotechnology, and the Institute of Drug Discovery, and elsewhere are essential to complement strengths in the radiobiology program. A sufficient “critical mass” capability should also increase funding opportunities for the radiobiology program. Thus rather than being an isolated unit, the radiobiology program could function as an important “node” to facilitate University efforts and initiatives in this field.