Our group is interested in understanding cellular responses to DNA damage. DNA damage occurs fairly regularly in all of us as a result of environmental factors such as increased exposure to DNA-damaging agents or from genetic factors such as decreased efficiency of normal DNA repair processes. In any organism, the capacity to sense and respond to DNA damage is vital for maintaining healthy functioning cells. Deficiencies in the ability of cells to sense and repair damage leads to neurodegeneration, immune deficiency, infertility and aging.
Using antibody arrays, we have identified several proteins and phosphoproteins as prognostic and therapeutic targets in triple-negative breast cancer (TNBC) and we are studying the effect of inhibiting these proteins on growth and invasive potential of TNBC cell lines in vitro. We will also study the role of these activated proteins in tumour biology and will perform knockdown studies in xenograft and syngeneic mouse models to control tumour formation and prevention of tumour metastasis.
In collaboration with David Fairlie (IMB), we are developing small molecules that inhibit DNA recombinase, Rad51, overexpressed in significant percentage of TNBC during disease progression. The development of these molecules have the potential to be used as a sensitising agent with conventional chemotherapies. Paclitaxel is a widely used chemotherapy in in triple negative breast cancer (TNBC) and there is a pressing need to identify mechanisms of resistance to standard chemotherapy in TNBC which has a high rate of aberrations in the PI3K pathway. We are examining the potential of utilising AKT inhibitors in combination with anti-mitotic drugs for the treatment of cancer. Combining other anticancer agents with targeted therapy to increase efficacy and minimise resistance will also be tested in TNBC.