Radiation Biology & dna rEPAIR

PROGRAM OVERVIEW

Radiation Oncology has been an integral part of the Lombardi Comprehensive Cancer Center since its inception. The Radiation Biology & DNA Repair (RBDR) Program is a multidisciplinary laboratory research effort with 17 members providing clinical and laboratory expertise. The goal of this program is to develop a comprehensive research program integrating investigations in basic radiation biology and molecular biology.

The current research areas within RBDR include radiation-induced signal transduction, molecular targeting for radiation sensitization of cancer cells, poly (ADP-ribose) polymerase (PARP) activation in apoptosis, roles of oncogenes in radiation resistance, and DNA damage and repair. All of these are directly related to underlying mechanisms of cancer formation or treatment.

The identification of factors associated with the responses of mammalian cells to ionizing radiation has been a major focus of research in radiation biology. More specifically, the ability to predict "radiation sensitivity" or "radiation resistance" of tumors relative to normal tissue tolerance has been identified as an important goal of clinically-related radiobiological investigation. Furthermore, understanding of the cascades leading to gene expression in response to ionizing radiation may permit future improvement of therapeutic interventions.

Recent insights into the molecular bases underlying cellular radiation response have been dramatic. Signal transduction pathways have been implicated in important roles in cellular responses to ionizing radiation. Induction of gene expression by these cascades under various conditions has been shown to result in cell cycle arrest, activation of DNA repair processes, and activation of apoptosis.

Through this research program, RB investigators have examined the molecular basis of the resistance of human tumor cells to killing by ionizing radiation. Through collaborative interactions of members of the Departments of Radiation Medicine, Biochemistry and Molecular Biology, a multidisciplinary strategy has been designed to pursue the mechanisms of action and therapy of tumor cells. The studies in this program use cellular, biochemical and molecular approaches to investigate the radiation-resistant and the radiation-sensitive cellular phenotypes as they may relate to the treatment of human cancers. Through collaborative interactions with the Molecular Targets and Developmental Therapeutics Program, clinical trials have been performed to translate this research to patient care.

The aims of the various projects are to:

Aim 1 - Characterize mechanisms of response of tumor cells to radiation.
Aim 2 - Identify molecules/pathways that may be targeted for therapeutic gain.
Aim 3 - Utilize this knowledge to develop translational oriented strategies.
Aim 4 - Understand mechanisms of radiation injury that lead to carcinogenesis.