Understanding the effects of immunomodulatory therapies on radiation response
Primary Supervisor: Dr Monica Olcina
Dying cancer cells are thought to be a rich source of tumour antigens and danger signals into the tumour microenvironment. Work from the Olcina lab has found that targeting complement can increase tumour cell death following radiotherapy which may in turn modulate anti-tumour immune responses. However, how to productively harness these responses to maximise productive inflammation while limiting normal tissue toxicity is still unclear. To uncover these mechanisms, we will explore modes of cell death following complement inhibition. The defence and repair responses mobilised following increased death will be explored, including their impact on key innate and adaptive immune responses in the tumour microenvironment. These studies will involve the use of cell and molecular biology techniques as well as in vivo mouse models. Flow cytometry, analysis of spatial transcriptomics and multiplex imaging will also be undertaken. The ultimate goal will be to understand how to effectively reprogram the immunosuppressive tumour microenvironment to trigger curative therapeutic responses.
Our group works in a collaborative and multidisciplinary manner. We are interested in a basic to translational approach to science, so we collaborate with clinicians and use patient samples or clinical data whenever possible. We also have experience working with in a range of model systems ranging from cell lines to in vivo mouse models. Students can also expect to receive training in bioinformatics and cell and molecular biology techniques. Students will have the opportunity to attend one national and one international conference throughout their DPhil. All members of the lab attend weekly lab meetings which include data presentations, troubleshooting and journal clubs. Dr Olcina meets with students in one-to-one meetings at least once every two weeks.
Olcina, M.M., Stavros, M., Nambiar, D.K., Kim, R.K., Casey, K.M., Woodruff, T.M., Graves, E.G., Quynh-Thu, L., Manuel, S. and Giaccia, A.J., 2020. Targeting C5aR1 increases the therapeutic window of radiotherapy. bioRxiv.
Olcina, M.M., Balanis, N.G., Kim, R.K., Aksoy, B.A., Kodysh, J., Thompson, M.J., Hammerbacher, J., Graeber, T.G. and Giaccia, A.J., 2018. Mutations in an innate immunity pathway are associated with poor overall survival outcomes and hypoxic signaling in cancer. Cell reports, 25(13), pp.3721-3732.