Phd Marius Wits

Research

Cancer is the second leading cause of death globally, despite recent therapeutic advancements. While Transforming growth factor-β (TGF-β) is a known oncogenic factor (by driving immune evasion, tumor stroma formation, and metastasis), it’s not yet a clinically approved therapeutic target. The major limitation is that current TGF-β therapeutics affect all cell types systemically, causing severe side effects. We aim to make TGF-β targeting drugs in a cell-selective manner for a more targeted and safer approach.

To do this, we learn from evolutionarily sophisticated mechanisms by which intestinal parasites hijack the TGF-β receptors and mediate immune evasion. The mouse intestinal nematode Heligmosomoides Polygyrus secretes TGF-β mimic proteins (TGMs) which can induce or inhibit TGF-β signaling on specific cell types only. We study how these TGMs alter TGF-β signaling and which host cell types and receptors they target. Subsequently, we use these findings to engineer novel TGM-based anti-TGF-β therapeutics to treat cancer.

Curriculum Vitae

After my bachelor’s Biology (2013-2018) and master’s Biomedical Sciences (2018-2020) at Utrecht University (UU), I pursued my PhD studies under the supervision of Prof. Marie-José Goumans and Dr. Gonzalo Sanchez-Duffhues at the Leiden University Medical Center (LUMC) (2020-2024). In this work, I studied dysregulated signal transduction in the two rare genetic diseases Fibrodysplasia ossificans progressiva and Pulmonary arterial hypertension. As such, I developed a novel molecular model to assess TGF-β specific small molecule kinase inhibitors and contributed to important translatable biological findings in these diseases. Further, I obtained a mobility fellowship to investigate one of our therapeutic leads in vivo under the guidance of Prof. Francesc Ventura at the University of Barcelona (UB). Currently, as a postdoctoral researcher in the group of Prof. Peter ten Dijke, I study novel anti-cancer therapeutics.