Andrew Vaughan, Ph.D.
Professor, Radiation Oncology
During the treatment of cancer with radiation and/or cytotoxic drugs a small number of individuals may develop a second malignancy, such as leukemia. It is known that the initiation of such a disease often involves the inappropriate joining of two specific genes – usually on different chromosomes. This process requires the DNA be broken within each gene and then linked or fused together. It has been thought that such a process occurred at random, making it difficult to suppress. Dr. Vaughan and his group have demonstrated that in the case of a specific fusion gene linked to the induction of leukemia, MLL, such DNA fragmentation and rejoining may occur as the DNA folds into a “kink”, driven by both enzyme action and local DNA sequence. This acts as a roadblock for the transcriptional process where information is read from the DNA. The collapse of transcription machinery at the roadblock may trigger DNA fragmentation and gene fusion. Understanding this process will help to design strategies for suppressing these second malignancies in those patients undergoing treatment for their primary disease, such as breast or lung cancer.
Matthew Coleman, Ph.D.
Associate Adjunct Professor, Radiation Oncology
Dr. Coleman is pursuing research to identify the cellular mechanisms associated with ionizing radiation (IR) exposures in humans. This work relies on using genomic and proteomic techniques to identify and characterize transcriptional networks, such as TP53, MYC and NF-kappaB, that play a role in controlling cell fate in response to IR exposures. Importantly, these regulatory pathways are also utilized by the cell to support cancer progression. Such information can be utilized for developing diagnostic assays and tools for biodosimetry as well as the treatment and prevention of cancer. Dr. Coleman is also very active in the development of advanced biochemical techniques using nanoparticles made of apolipoproteins and phospholipids called nanolipoprotein particles (NLPs). NLPs closely mimic the cellular membrane bilayer, and represent an ideal platform for characterizing membrane proteins involved in signal transduction. The NLPs are also proving useful for drug delivery, immuno-modulation and in vivo imaging in the treatment of cancer.
Jian-Jian Li, M.D., Ph.D.
Professor, Radiation Oncology
Dr. Li is studying a small sub-population of tumor cells, called cancer stem cells, which are particularly radiation resistant. Such cells, if they survive treatment, may be responsible for treatment failures. Using modern molecular techniques he has found that a specific protein, NF-kappaB, may be a key regulator of this key group of cells. By manipulating both this protein and/or the pathways and processes it controls, it may be possible to enhance the killing of this key subgroup of cells. In an allied project Dr. Li has also found that the same protein (NF-kappaB) may also regulate the adaptive response. This is a process whereby a small dose of radiation may diminish the effects of subsequent doses. This is clearly a concern for tumor treatment but might be used to advantage to protect normal tissues exposed to irradiation.