CAREER: Mechanisms of Drug Resistance in a Responsive Biomaterial Platform

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Non-Technical:This CAREER award by the Biomaterials program in the Division of Materials Research to University of Massachusetts at Amherst is to develop novel materials that can capture human tissue properties in a controlled, reproducible, and economical fashion. It is cofunded by the BioMaps program and funds from the ENG/CBET/BBBE program. At present, new drugs are developed by screening hundreds of possible candidates against cancer cells grown on plastic surfaces. Drugs that show potential are further tested in animals, and anywhere from zero to a handful of candidates could make it through this process, where they are then taken to clinical trials. Drug candidates that appear successful in cells on the plastic surfaces often fail in clinical trials. Overall, this process is long and not cost effective. The biomaterials that are being studied have potential use in understanding how cancer cells respond to drugs in an environment that mimics human tissue, and thereby overcomes some of the drawbacks of the present approaches. With this award, the PI plans to develop new educational opportunities for students from high school to graduate levels. High school students, especially women will be trained in the PI's laboratory during the summer months, where these students can learn how to do cell culture and 3D printing techniques and to observe how cells move and grow on different material surfaces. Undergraduate students will be trained in creating new pathways to take ownership and authorship of their learning experience, resulting in educational modules that can be used across the nation. At the graduate level, the focus will be in recruiting highly capable students from underrepresented groups across the nation to become the next leading scientists working at the interface of materials and biology. Technical:The ability of cells to resist chemotherapy impacts cancer patients around the globe. A core problem of the current drug screening techniques that utilize plastic multi-well plates is that it fails to account for a cell's native material microenvironment. This CAREER project will take a transformative approach to drug screening by quantifying cancer cell responses to drugs in a biomaterial platform mimicking the rapidly evolving material properties of the tumor microenvironment, specifically a material microenvironment that is continually remodeled by resident mesenchymal stem cells (MSCs). This proposal will use a high-throughput biomaterial platform to determine how three dimensional matrix stiffness, integrin binding, and soluble growth factors and cytokines impact cancer cell response to drugs. The underlying hypothesis is that physical and biochemical cues from an MSC-remodeled extracellular matrix (ECM) interfere with the efficacy small molecule drugs, and that targeting the MSCs, not the cancer cells, can halt this drug resistance. The results from this proposal would transform our fundamental understanding of the role that the physical environment plays in interfering with small molecule drugs. The PI will leverage CAREER funding to increase educational opportunities in bioengineering at three levels: high school, undergraduate, and graduate. The PI has already created a new summer laboratory program at University of Massachusetts at Amherst that teaches high school students cell culture and advanced microscopy techniques. Over the next few years, the PI plans to create new educational modules for undergraduate students that are specifically aimed at self-directed learning techniques and fostering creativity and teamwork in the classroom. Additionally, the PI plans to expand recruiting efforts nationwide, in collaboration with the Diversity Institute at the campus, to bring more qualified students from underrepresented groups to campus, and train them to become the future leaders in science and engineering.