Radiation and Cancer Biology Division

The Radiation and Cancer Biology Division performs innovative, basic and applied research and works to translate basic research results into clinical practice; provides superior training and education of basic scientists and clinical practioners with the goal of developing future leaders in the field; and contributes to the professional development and recognition of faculty and staff members.

Director Joseph L. Roti Roti, Ph.D.
Telephone 314-362-9789
E-Mail rotiroti@radonc.wustl.edu
Address Radiation Oncology Department
Radiation and Cancer Biology Division
4511 Forest Park Blvd.
St. Louis, MO 63108

Training Programs

Graduate Course: Cell Biology of the Stress Response
Resident Training: Classroom and Research Mentorship
Undergraduate: Research Mentorship

Radiation and Cancer Biology Faculty:

• Dennis Hallahan, M.D., Department Chairman
• Joseph L. Roti Roti, Ph.D., Director
• Andrei Laszlo, Ph.D.
• Hsiu-san Lin, M.D.,Ph.D.
• Ryuji Higashikubo, Ph.D.
• Buck Rogers, Ph.D.
• Shaun P. Scott, Ph.D.
• Qin Yang, Ph.D.
• Junran Zhang, M.D., Ph.D.
• Susana Gonzalo, Ph.D.

Research Overview

The Radiation and Cancer Biology Division conducts research resulting in new basic
knowledge of:

• The biology of malignant tumors and cancer cells.
• The biological mechanisms of anticancer therapeutic modalities (e.g. radiation, hyperthermia and drugs).
• The normal tissue effects of cancer treatment, including stress responses and the biological effects of RF radiation.

Work in the Division is almost entirely cellular and molecular in terms of the biological level pursued. The major focus of ongoing work is elucidation of the molecular mechanisms of cellular response to ionizing radiation exposure and exposure to heat shock. Specifically, the cellular responses under investigation included alterations of cell proliferation, repair of DNA damage, changes in gene expression and the failure of specific cellular functions that lead progressively to cell death.

The faculty has developed many significant research efforts. Dr. Horikoshi has several active projects ongoing in his lab, i.e., studying the role of p53 in stress resistance and signal transduction and apoptosis. He has discovered six new genes that respond to mutant p53. Dr. Hunt recently completed development of an hsp70 knockout mouse. He has shown that radiation-induced DNA damage in transcription elements inhibits the binding of transcription factors. Dr. Laszlo has been studying the effects of hyperthermia on the DNA repair proteins, Ku86 and Ku70 and the effects of heat on DNA supercoiling and radiosensitization. Dr. Roti Roti’s work includes three components:

1) nuclear matrix proteins and radiosensitivity,
2) cell killing by hyperthermia and
3) the biological effects of RF radiation.

Work showing that a redox sensitive protein plays a role in DNA anchoring was just published and featured on the cover of the Journal of Cellular Biochemistry. Recent work has shown that 41.1°C hyperthermia causes the DNA repair protein, Mre11, to delocalize from the nucleus and dissociating from one of its functional partners, Rad50. This appears to radiosensitize tumor cells by increasing the a parameter. The studies of the effects of RF radiation from cellular telephones are using the latest gene chip and proteomic technologies. The RF program has recently received $75,000 per year for three years from the Department of Defense to study changes in gene expression following RF exposure. Dr. Higashikubo is completing studies on the effects of small temperature increases on the order of 1 - 2°C on cell proliferation.

The faculty currently has the following expertise in place: heat shock proteins, hsp70, hsc70, nuclear effects on cell killing, signal transduction, gene therapy, hypoxia and radiation sensitivity modifiers. Dr. Tej Pandita’s (July, 2002) expertise is on telemers, telomerase and genomic instability. Dr. Buck Rogers (September, 2002) has expertise on molecular-functional imaging and gene therapy.