Detailed description of research projects
Human papillomavirus (HPV) related Head and Neck Cancer (HNC) and specifically oropharyngeal cancer (OPC) has been increasing in the last decade. In particular, HPV16 is involved in HNC tumorigenesis and in general HPV positive HNC patients have a more favorable prognosis in comparison to HPV negative ones. Indeed, HPV positive (HPV+) and HPV negative (HPV-) tumors are distinct entities as shown by clinical behavior, treatment outcome, and molecular profile. This is highly significant because HPV+ and HPV- HNC have markedly different disease profiles, although their treatment options do not yet mirror these diversities. Molecularly targeted therapy has potential in the treatment of these cancers, but there is still much to learn on existing targets/possible drugs.
Both Histone Deacetylases (HDACs) and TGFb pathway targeting are being looked upon as promising approaches. Importantly, HDACs activity, epigenetic remodelling, TGFbpathway and metabolism can be reciprocally regulated depending on cell metabolic status. Our goal is to identify novel therapeutic targets by unravelling unique and distinct mechanisms controlling these cellular processes in HPV+ vs HPV- HNC, taking also into account sex differences for this disease. Indeed, we approach our research projects with a proper sex/gender lens (link to LIBRA teaching module).
We have recently published that the SUMO E2 conjugating enzyme Ubc9 is regulated via autophagy, and that the expression of HPV E6 and E7 oncoproteins impairs this pathway leading to Ubc9 accumulation. Importantly, in human tumors, HPV drives Ubc9 up-regulation at a very early stage of head and neck tumorigenesis, underscoring the importance of Ubc9 in HPV-mediated carcinogenesis. We are thus dissecting the molecular mechanisms underlying Ubc9 regulation in HNC, utilizing HNC cell lines, human primary tumors and keratinocytes.