Douglas Bishop, Ph.D.

Basic Research
dbishop at midway.uchicago.edu

Dr. Bishop's group focuses on the mechanisms cell use to repair broken DNA molecules. DNA breaks occur during normal cell growth, during meiosis, the special cell divisions that gives rise to gametes, and when cells are exposed to radiation. DNA repair is relevant to cancer in two ways. First, when normal cells fail to repair DNA, mutations occur and these mutations can lead to cancer. Second, many effective cancer treatments, such as radiation treatment, and some forms of chemotherapy, work because they kill tumor cells by damaging tumor cell DNA. In this case, DNA repair contributes to treatment failure by protecting tumor cells from the effects of therapeutic agents. Dr. Bishop's lab uses genetic techniques to study the proteins that carry out a form of DNA repair called "recombinational repair" in yeast and vertebrate cells. The lab has recently identified a group of proteins that work as "assembly factors" to build the protein complexes needed to repair DNA. One of the proteins that appears to play the role of assembly factor is BRCA1p which is encoded by the BRCA1 gene. The BRCA1 gene helps prevent cancer, people who inherit defective copies of this gene have a high risk of breast cancer and other malignancies. In addition to studying recombination genes and proteins in more detail, Dr. Bishop's group is working in collaboration with Dr. Weischelbaum's group to identify inhibitors of recombination complex assembly. Their experiments have already provided evidence that assembly inhibitors will increase the effectiveness of certain types of chemotherapy.

In addition to studying the repair process itself, Dr. Bishop's group studies proteins that help cells recover from DNA damage by stopping cell growth when damage is present. The arrest caused by these proteins allows time for the DNA repair process to occur. Recent work from the Bishop lab indicates that the same proteins that halt cell growth after DNA damage also appear to be important for generating or maintaining normal chromosome structure.