Harnessing Stem Cell and Tissue Engineering for Cancer Research

Current cancer research is hindered by the limitations of existing experimental systems, which fall short in demonstrating concordance with human studies. Refined methods and models are urgently needed to bridge the gap between cell line, animal-based and clinical research. Here, I describe my research to apply innovative engineering approaches to study long-standing questions in cancer research, in an era in which stem cell biology, tissue engineering and genomics are approaching a new level of sophistication.  My currently developed cell culture models based on directed differentiation of human pluripotent stem cells reveal why certain constellations of genetic changes drive carcinogenesis in specialized human cell lineages. These tractable experimental systems enable studying cancer in greater depth than has been possible before, using genetically defined human cells that can be characterized at the single cell level. Another line of my work is to address the problem arising from species variation that animal based cancer models can be considerably different to human cancers. I engineered an ex vivo colon cancer model by recellularization of human native matrix with human primary cells. I followed to demonstrate the significance of the organotypic model in identification of cancer driver genes by combining transposon-based mutagenesis. Finally, I will describe using chemokine-targeting to develop orthotopic xenograft mouse models that recapitulate the vast majority of recurrent mutations in patient samples without requiring surgery. Importantly, I employed mouse blastocyst microinjection techniques to extend this approach and model primary human cancers in immunoproficient mouse hosts.