Our laboratory is interested in basic and translational research on the molecular genetics of cancer, in particular urological (prostate, bladder and kidney) and female (breast and ovarian) cancers. Our studies involve the analysis of:
This research is coupled with translational approaches involving the development and refinement of new, sensitive molecular techniques that we hope to use to diagnose cancer earlier, as well as to improve the accuracy of prognosis and eventually direct treatment of sporadic cancers.
Most tumor suppressor genes identified to date have been from familial cancers where linkage studies were possible. The challenge ahead is to identify the important genes in major sporadic cancers, such as prostate, breast and bladder, which are numerically far more common than familial cancers and where linkage analysis is not possible. The increasing number of markers, mapping data and genomics technology will simplify the cloning of these genes after location. As well as identifying the genetic alterations that drive cancer, it is important to study how often these alterations occur and at what point in the development of the cancer they occur. Homozygous deletion and promoter methylation have recently been added to point mutation and loss of heterozygosity (LOH) as mechanisms of mutational inactivation of suppressor genes. Detecting and understanding these mutations is extremely important. The construction of molecular genetic progression models allows the identification of early genetic events, which are useful for diagnosis, while an ordering of events offers the possibility of molecular staging for prognostic assessment. Using novel, highly sensitive molecular assays, which detect genetic alterations indicative of cancer, we are investigating novel approaches to the early detection of cancer by screening bodily fluids that surround, drain from, or access the organ of interest using, where possible, non-invasive sampling in patients at risk of cancer. In addition, to establish a molecular prognosis we screen for minimal residual disease in surgical margins, nodes and bodily fluids of patients with cancer.