This CAREER award by the Biomaterials program in the Division of Materials Research to Indiana University-Purdue University Indianapolis is to fund an interdisciplinary research project that integrates knowledge and technology from polymer science and engineering, peptide and macromolecular chemistry, as well as cellular and molecular biology related to cancer stem cells (CSCs). CSCs are highly metastatic and resistant to drug treatment. This research will develop biomaterial matrices with controllable biophysical and biochemical properties that enable both exploratory and mechanistic studies at cellular and molecular levels. The research results from this study will be integrated into the PI's teaching of both undergraduate and graduate students. The research outcome will be disseminated through conventional venues (i.e., presentations and publications), and will be integrated into diverse educational activities that are designed to promote the awareness of both biomaterials and cancer biology. To broaden the impact of this project, the educational and outreach activities will include participants at the campus, regional, and international levels. The palnned outreach activities are designed for students from the young and underrepresented groups (6th graders to high school students). Furthermore, free workshops incorporating hands-on activities on hydrogel fabrication will be offered to high school educators. Introductory level topics on biomaterials and cancer stem cell biology will be incorporated into all activities.
The goals of this CAREER project are to develop modularly crosslinked 3D hydrogels with a built-in mechanisms for tuning matrix properties to understand the self-renewal, differentiation, and drug responsiveness of cancer stem cells (CSCs). The research objectives of this project are to synthesize hydrogels with covalent crosslinks and reversible supramolecular linkages for repeatedly tunable hydrogel stiffness. Using this dynamic hydrogel system, it would be possible to evaluate the effects of matrix properties on self-renewal and differentiation of CSCs. This material platform will also allow hypothesis-driven studies related to stiffness-dependent activation of Notch signaling, a pathway involved in drug resistance in CSCs. This research will be integrated into educational activities that involve students, especially those from the underrepresented groups from 6th graders to graduate students, high school educators, and international audiences. Specifically, with this CAREER award, the PI will mentor undergraduate and graduate students in research and learning, and will offer workshops and hands-on activities to minority students and high school educators. In addition, the research results of this project will be disseminated internationally through collaboration with scientists in Republic of Korea.
