Grant: Operating Grant

Poly(ADP-ribosylation) is a modification to a protein that is important for cell growth, DNA damage and changes in the expression of other proteins. Proteins that cause this modification are called poly-ADP-ribose polymerases or PARPs. Blocking the action of PARPs is a potentially promising anti-cancer therapy. TiPARP is a member of the PARP protein family that is regulated by another protein called the aryl hydrocarbon receptor or AHR. AHR mediates most, if not all, of the toxic effects of environmental contaminants called dioxins. However, the biological function of TiPARP and its role in human disease, as well as its potential role in AHR action remain elusive. The overall objectives of this study are to elucidate the mechanism of action of TiPARP, determine how TiPARP protein expression is regulated and determine its role in the AHR signalling. To attain these objectives, we will use molecular and cellular biology techniques in conjunction with biochemical approaches and animal models. By determining the function of TiPARP and its role in AHR action, this research has the potential to lead to the development of new strategies for human disease and enable better estimates of the health risks associated with exposure to chemicals that activate AHR.