Conner Giles, NIH Trainee 2020-21cgiles@umass.edu
Graduate Program: Chemical Engineering
Lab: Jungwoo Lee
Research Interests: Engineering the tumor microenvironment to investigate dormancy
Research Summary
Cancer is a resilient disease characterized by relapse after years. Metastasis, the process by which cancer cells split from a primary tumor mass, enter circulation, and seed distant sites, is a central factor in cancer’s resilience. Disseminated cancer cells express increased resistance to therapy, limiting the efficacy of treatment in the long term. While our methods for treating cancer have greatly improved over the years, long-term disease-free survival is not guaranteed. Our lab has shown in our animal models that adjuvant chemotherapy and non-chemotherapy mice experience metastatic regrowth at similar rates and suggests that more robust strategies for targeting the dormant environment are needed. Targeting the dormant niche requires an understanding of the signals and metabolic pathways that promote either proliferative or nonproliferative phenotypes. Dr. Jungwoo Lee’s implantable biomaterials provide a platform to investigate these pathways, and offer a unique opportunity to study the metastatic niche in which cancer reawakens.
These implantable biomaterials are inverse colloidal crystals composed of polyacrylamide and coated with collagen or other extracellular matrix proteins. The porous structure of the biomaterials instigates a unique and valuable foreign body response that drives strong cell recruitment to the material’s surface upon implantation. We use this immunogenic response to drive circulating cancer cells produced by spontaneous mouse mammary tumor animal models to the biomaterial scaffold. Many in-vivo models fail at this point, as the host animal becomes moribund with tumor mass. We surpass this limitation by transplanting the scaffold environment to a secondary host animal which slows the tumor progression. Serial transplantation establishes a premetastatic niche ideal for evaluating microenvironmental regulation. I aim to extend this implantable niche model to probe the relevance of particular tissue compositions and niches. For example, our lab has noted differing growth rates in tumors engrafted into subcutaneous tissue as opposed to liver tissue, and I plan on investigating how these two tissue spaces can alter cancer niche regulation. Additionally, the flexibility of the inverse colloidal crystal biomaterial scaffolds allows for controlled modifications to the tumor niche, which I plan to exploit in order to investigate how specific extracellular matrix proteins affect dormancy-promoting pathways.
Investigating the mechanisms by which tumor cells and their microenvironments interact is crucial to developing effective cancer therapies. Flexible, powerful biomaterial based strategies enable unique opportunities to examine the role of the tissue environment in cancer regulation.