PhD Marten Hornsveld

Research:

As a signal transduction expert, my research aims to understand inter-cellular signaling between cancer and healthy cells and how to apply this knowledge to create therapeutic strategies. I focus on the role of TGFß-signaling in the stroma of pancreatic cancer as this pathway is heavily involved in stimulating fibroblasts to associate with cancers (CAFs) and support tumor survival and progression. To do so, I established a 3D co-culture system of patient derived pancreatic tumor organoids with pancreatic stellate cells (PSC), the fibroblasts of the pancreas and use this system to study TGFß mediated effects in growth factor signaling and metabolic activity in both PSCs and cancer cells. By constructing genetic cell-type specific TGFß (in)activation strategies in these co-cultures, signal and metabolic pathway activity can controllably mapped to learn how different cell-types affect each other. To target potential inter-cellular signaling vulnerabilities, I use a bi-cyclic peptide recognizing PDGFRß on activated fibroblasts. This peptide can be used as a vehicle for CAF specific drug delivery. Combined, try to get a better fundamental understanding of pancreatic cancer and its interaction with the stroma and identify novel opportunities to detect & deter supporting CAFs.

Curriculum Vitae:

I studied Biotechnology (BAS, HU) and Cancer, Genomics & Developmental Biology (MSc, UU) in Utrecht.  During my studies I did various internships in the labs of Jos Jonker (NKI), Jaqcueline Deschamps (Hubrecht institute), Susanne Lens (UMCU), Helder Maiato (IBMC, Porto) & Benjamin Rowland (UMCU). For my PhD I joined the lab of Boudewijn Burgering and Tobias Dansen at the UMCU, where I focused on the challenging question: What is the role of FOXO transcription factors in cancer progression? I elucidated the fundamental molecular signalling role of FOXOs using mouse models for breast cancer. Additionally, I closely collaborated with Philips to translate our understanding of FOXOs into clinical application as part of the OncoSignal platform. Lastly, we uncovered that FOXOs are part of a novel DNA-replication stress checkpoint in S/G2 phase of the cell cycle, a function of which we are currently trying to elucidate the molecular mechanism.