PhD conferral A. Abulikemu
Aula, Vrije Universiteit Amsterdam
Signaling at the tumorigenesis-inflammation interface: developing systems immunology to resolve a paradox
Prof. H.V. Westerhoff, Prof. S.M. van Ham and Dr M. Barberis (copromotor)
Amsterdam Institute for Molecules, Medicines and Systems
Earth and Life Sciences
Systems biology: cancer and inflammation, personalized?
Today, cancer continues to be one of the most common life threatening diseases in the world. An inflammatory environment may contribute to tumor growth at the early stages of cancer. Immune cells in the inflammatory environment may affect tumor growth through acute or chronic inflammation, and thereby studying immune cells is part of a systematic approach towards combatting cancer. Targeting mast cells amongst the immune cells appears to be regressive to tumor expansion, and inhibition of mast cell activation has proven to be a therapeutic approach to cancer-related inflammation. In addition, inflammation appears to play an important role in many other multifactorial diseases. However, inflammation is a complex network phenomenon. The aim of Abulikemu's PhD project was to exemplify a new approach to the understanding of inflammation, i.e. one that capitalizes on the network nature of the phenomenon: systems immunology.
In his PhD project, Abulikemu build a systems biology model for innate immunity around mast cells, that simulates the occurrence of acute and chronic inflammation, and demonstrates how the action of peptide-based drugs on chronic inflammation may be predicted. This inflammatory model was extended to a cancer model, to assess the occurrence of indicators of inflammation such as mast cells and TNF-α in tumor tissue, and to test a proposed drug in silico. Next, Abulikemu developed analytical methods to inspect validity of the model. The related methods, such as Bi-stability for steady state and sensitivity analysis, are integrated with empirical analyses. Lastly, the further perspectives of the systems immunology here developed are discussed in his thesis.
Taken together, Abulikemu’s findings not only imply a promising approach for targeting tumor-associated inflammation (see figure) but also lead to a further support of clinical cancer therapy by systems approaches.