Research Fellows Directory
Dr Martin Cohn
University of Oxford
Fanconi Anemia (FA) is a rare but very serious disease. The underlying DNA repair pathway, which is deregulated in FA patients, is critical to ensure genomic stability, and FA patients are consequently at high risk of developing cancer. Patients typically do not survive beyond their teens. Apart from severe bone marrow failure, the most common causes of death in FA patients are blood cancers and solid tumors. Treatment of these patients in the clinic is very difficult due to their hypersensitivity to chemotherapeutic drugs. The patients are hypersensitive because of the underlying defect in the FA pathway in their cells.
At present, we understand some molecular aspects of the FA pathway. It involves at least 19 proteins, where a central protein is called FANCD2. The activity of this protein is tightly regulated in the cell. After cells experience DNA damage, FANCD2 is rapidly translocated by an unknown mechanism to sites in our genome where its activity is required. This event is critical to the DNA repair process. A key goal of our research is to elucidate this unknown mechanism of recruitment. Intriguingly, the exact molecular function of FANCD2 in the DNA repair process is currently not understood. Addressing these important questions is a part of ongoing research.
Our research will provide novel insight into how the Fanconi Anemia pathway operates. But perhaps equally important, since multiple proteins from other DNA repair pathways are also recruited to damaged DNA by unknown mechanisms, it is likely that understanding the FA pathway, may also shed light on how other essential DNA repair pathways operate.
Eventually, the goal is to develop new and better strategies for treatment of the lethally ill FA patients. Obtaining molecular insight into the FA pathway may lead the way to achieve this goal.
Interests and expertise (Subject groups)