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RESEARCH ACTIVITIES

The radiation dosimetry laboratory (RDL) is engaged in the study of radiation effects on solid and/or biological systems. The goal is to use the knowledge gained from these studies to develop new types of radiation dosimetry systems and techniques for radiation oncology applications and for radiation protection and nuclear nonproliferation uses

Medical Applications

Research activities include photon and electron beam dosimetry for teletherapy and brachytherapy treatments. Recent clinical research areas include: effect of respiratory-induced organ motion on dose distribution of IMRT (Intensity Modulated Radiation Treatment), radiographic film dosimetry, radiochromic film dosimetry, small electron beam dosimetry, interface dosimetry, calibration of brachytherapy sources with a well-type dose calibration, total body irradiation, total skin irradiation, wedge factor dependence on depth and field size, stereotactic brain implants with high-activity I-125 seeds, ultrasound guided prostate implant with Pd-103 seeds, measured dose to ovaries and testes from Hodgkin's fields, air cavity effects on radiation dose to the larynx, and dosimetric characteristics of an electron collimating system for intraoperative radiation therapy. (Professor Niroomand-Rad and staff).

Raf-1 Protein Kinase, Radiation Response and Signal Transduction

Raf-1 protein serine/threonine kinase plays an important role in mitogenic and damage-responsive signal transduction pathways. Understanding of the mechanisms and components of this signaling cascade is critical to the development of new therapeutic strategies of cancer. The major focus of our current research is to examine the components of Raf-1-mediated signal transduction pathways in human cancer cells. These investigations are based on the premise that a transient or constitutive modulation of Raf-1 expression and activity leads to a series of biochemicals and molecular changes which at least in part, contribute to the modification of growth and radiobiological responses of tumor cells. An important translational gain from these studies has been the demonstration of raf antisense sequence-specific sensitization of tumor cells to the toxic effects of gamma radiation. Experiments have been initiated to test the in vivo efficacy of antisense raf oligodeoxynucleotide as a biological radiosensitizer. If successful, these observations will be directly translatable into clinical investigations. Furthermore, experimental therapeutic approaches established during the course of these studies will be applicable to other newly-identified, and potentially novel components of the Raf-1-mediated signaling response.

Radiation Carcinogenesis in Human Cells

Ionizing radiation is a lethal, mutagenic and carcinogenic agent in many biological systems and has the potential to participate at many in the multi-step process of cancer development. An understanding of the biological consequences of radiation damage is important because of occupational, diagnostic, and therapeutic uses of ionizing radiation. In particular, we are using ionizing radiation to transform various human epithelial cell types (breast, prostate and skin keratinocytes) to a malignant phenotype. We have recently shown that immortalized human keratinocytes and prostate epithelial cells can be transformed and develop tumorigenic potential after exposure to x-rays or neutrons. Our overall goal is to identify the cellular genes that are either activated or inactivated during the development of the radiation-induced malignant phenotype to provide a molecular basis for radiation carcinogenesis in human cells.