Development of Metastatic Organ-on-a-Chip for modelling the role of sex steroids in Bladder cancer metastasis to bone

Bladder cancer (BCa) is the 5th most common cancer in Europe, with an annual economic burden of €5 billion.

Despite efforts aimed at early detection and targeted therapies, the development of metastatic BCa (5%) remains a major cause of mortality (patient survival rate of only 21 %). Recent evidence has strongly implicated a role of Bone Morphogenic Proteins (BMPs) in BCa progression. However, their regulation remains poorly understood and their role in metastatic BCa remains to be elucidated.

Moreover, there is paucity of understanding regarding the gender disparity in BCa, whereby men are 4 times more likely to be diagnosed, compared to women, who have worse prognosis.DeMOBilise seeks to address this critical gap in the knowledge by investigating the synergistic role of sex steroids (SS) and BMPs in BCa bone metastasis.

This will be achieved by using single cell multiomics and CRISPR gene editing, coupled with state-of-the-art Organ-on-a-chip (OoC) technology and spatially resolved imaging of the bone perivascular niche within the OoC.

This study will thereby investigate, at an unprecedented level of detail, the functional role of BMP signalling and its synergy with SS in BCa metastatic processes.I will spend 2-years at Columbia University (USA) expanding my skills in cancer models and single cell sequencing and also acquiring a new skillset in OoC fabrication.

I will return to the University of Limerick (Ireland) and receive training in steroidogenesis, high-dimensional imaging and mass spectrometry.

Additionally, I will have a 6-month Non-Academic Placement in the start-up company Hooke Bio, who specialize in the development and utilisation of high through-put microfluidic systems for 3D microtissue drug screening.

I will be immersed within a multidisciplinary team with expertise in OoC fabrication, bone metastasis, and 3D cancer modelling that will support me in meeting my research/training objectives and prepare me for a career as an independent researcher.