Dennis McCance, PhD
Department of Pathology
Cellular and Molecular Oncology
The goal of my recent research is to determine why HPV positive oro-pharyngeal cancers have a better prognosis than human papillomavirus (HPV) negative cancers at the same site. The virus most commonly associated with these cancers is HPV type 16 (HPV-16). We believe that the p63 family of transcription factors plays a role through the regulation of differentiation, proliferation and migration, with other transcription factors. There is evidence that the ratio of expression of the six p63 isoforms is important of keratinocyte homeostasis and that this is disrupted in oro-pharyngeal cancers and also, we have show that E6 protein of HPV-16 regulates the level of p63 in keratinocytes. In addition, there is now evidence of p63 mutations in 12% of cancers. We have completed ChIP-seq experiments to map the p63 and p53 binding sites globally in the presence and absence of DNA damage and have validated a number of these sites. We are now using this knowledge to determine the genes regulated by p63 and mutant p53 that are involved in proliferation and invasion. The first of these genes researched so far are SRC and FAK and we have shown that both are essential for invasion in our 3-dimensional keratinocyte organotypic model and are also up-regulated in oro-pharyngeal cancers.
I have been the primary mentor of 22 PhD students.