PhD Candidate Profile: Stephanie Nemec

What is your research about?

My research investigates mechanical properties of the stroma formed by cancer-associated fibroblasts (CAFs) in pancreatic cancer (PC). CAFs bidirectionally communicate with pancreatic cancer cells and are thereby activated to myofibroblast-like cells producing the collagen-rich, highly fibrotic stroma surrounding the tumour, which is a clinical characteristic of pancreatic ductal adenocarcinoma (PDAC).

Existing in vitro models of PDAC rely on the use of pancreatic cancer spheroids or embedding the cells/spheroids in biomaterial such as matrigel, collagen I, and other hydrogels. Mechanical interactions and biological signals within the tumour microenvironment greatly influence cancer progression and invasion. Thus, we engineer extracellular matrices (protein micropatterns) to precisely tune mechanical properties such as interfacial geometry and stiffness to observe cell responses. We stamp fibronectin on non-adherent polyacrylamide hydrogels to organize cells into defined geometries. Our protein micropatterned technique with heterotypic cultures shows distinct spatial distribution of murine pancreatic CAFs (‘corralling’) in confined 250μm diameter circles, as well as human PC. This is reflected by the assembly of cancer cells in the middle of the circle pattern with the CAFs surrounding them. The development of novel microenvironment models of cancer and CAF co-cultures are aimed towards a better understanding of investigating invasion, progression, and metastatic potential of PC closely reflecting human disease biology.

What is the translational application of your research?

Current PC research relies on gold standard mouse models as a first in vivo test of drug therapies; however due to the heterotypic and complex nature of pancreatic cancer, drug response in such models varies widely due to the dense stromal structure acting as a physical drug barrier. Our model enables testing a range of stromal features including shape, stiffness and CAF-cancer cell ratios using patient-derived cells.

Developing a panel of diverse micro-tumour environments will allow for testing a cocktail of drug combinations in weeks, compared to the animal models’ month-year time frame. Further advantages of our model system are the relatively easy processability for analysis by imaging, quick identification of drug candidate response, and probing mechanistic pathways; ultimately yielding faster therapeutic responses with potential to scale.

How would the TCRN PhD top-up Scholarship help you succeed?

The TCRN PhD top-up Scholarship provides an excellent opportunity to connect to the TCRN network and being part of this network would certainly prove to be most valuable for my further establishment and professional competence in my field. I am interested in determining the commercialisation potential of our research technology and value the connections and interactions with clinicians and fellow researchers. It is my goal to see my research advancing and helping physicians and pancreatic cancer patients.