The Department of Radiation Biology was initially established to study the fundamental mechanisms of radiation resistance in cancer cells and to find a solution to modulate radiation resistance. The department currently has several research groups working on different aspects of radiation biology under its chair, Binghui Shen, Ph.D.
The major focus of Dr. Shen’s group is on the mechanistic roles of nucleases in DNA replication in the nucleus and mitochondrion and in cellular responses and repair of DNA damage induced by environmental insults such as ionizing radiation. The team employs multiple approaches such as crystallographic, biochemical, yeast and mouse genetic techniques to study these phenomena. In collaboration with the Lung Cancer Program, a subgroup of the Shen laboratory led by Li Zhong, Ph.D., is developing proteomic approaches for cancer diagnostics.
Lab studies led by Fong Fong Chu, Ph.D., aim to understand the role of oxidant and antioxidant enzymes in inflammation in the ileum and colon. Her lab also uses genetic approaches to identify genes that might be linked to inflammatory bowel (IBD) disease and to identify the mechanism by which dietary factors influence IBD in mice.
The laboratory of Jeremy Stark, Ph.D., investigates the repair of chromosome double-strand breaks, which are formed during a number of cancer treatment regimens, including radiation therapy. In particular, this lab is interested in the mechanistic overlap between different repair pathways as well as how individual mechanistic steps are prone to generating mutations.
A set of proteins belonging to the RECQ family of DNA helicases are among the cancer suppressors linked to DNA repair, replication and genome maintenance. During the course of evolution, RECQ genes appear to have been amplified and diverged from a single copy of the RECQ gene in bacteria and yeast to five RECQ homologs in humans. The human RECQ proteins share many similar biochemical properties in vitro, yet these proteins are not redundant, as mutations in different RECQ proteins lead to different clinical syndromes. In addition, a defect in one RECQ protein is sufficient to cause cell transformation and tumorigenesis, and this defect cannot be compensated by other RECQ proteins. The long-term agenda of Yilun Liu, Ph.D., is to dissect the functions of individual RECQ proteins in human cells, and these studies will allow her lab to compare the similarities and differences among the RECQ proteins. Through these comparisons, the Liu laboratory can then understand what aspects of genome maintenance and DNA metabolism are required for normal development and cancer prevention.
The laboratory of Robert Hickey, Ph.D., works on the structural and functional properties of proteins involved in DNA replication and repair. The recognition that some of the proteins involved in these two processes are modified by post-translational modifications that differentially affect their function in malignant and nonmalignant cells has led to a set of investigations directed toward identifying the differences in post-translational modification, and exploiting these differences to create diagnostic reagents capable of selectively identifying cancer cells versus noncancer cells, and therapeutic agents capable of selectively killing cancer cells, while causing little or no damage to normal cells. The lab has recently turned its attention toward characterizing the regulatory factors responsible for the differential post-translational modification of proteins like proliterating cell nuclear antigen (PCNA) in cancer versus noncancer cells. The lab’s immediate goals are to identify the protein methyltransferase/esterase responsible for creating the differences in the extent of methylesterification of PCNA between cancer versus noncancer cells; identify the regulatory factors modulating the esterification process; and determine the functional consequence of differentially modifying PCNA in these two types of cells.
These groups share a common interest in radiation-induced DNA damage and repair and radiation resistance. The principal investigators and their associates will direct efforts in radiation research toward fulfilling departmental goals, working in close collaboration with radiation oncologists in the parental division and with other scientists.