Bioluminescent imaging of NF-κB and Wnt signaling activities and their synergistic co-activation in cancer
Funded by the UT CORNET multidisciplinary research program
NF-κB and Wnt signaling pathways are vital regulatory mechanisms for development and homeostasis of cellular functions. Dysregulation of both pathways have been implicated in a wide range of pathologic conditions, including cancer. Aberrant NF-κB and Wnt signaling activities have been observed in many types of cancer, and are being intensively investigated for their roles in tumor initiation, progression, metastasis, and development of therapeutic resistance. Recent studies also imply that co-activation of NF-κB and Wnt pathways could synergistically promote cancer stem cell-like properties and enhance resistance to chemotherapeutics. To assist in the understanding of their roles in cancer pathology and development of anticancer therapeutics targeting these pathways, the main goal of this proposal is to develop autonomously bioluminescent imaging approaches to enable continuous, real-time monitoring of NF-κB and Wnt signaling activities for both in vitro drug screening and in vivo cancer progression imaging applications. Our interdisciplinary team will develop bioreporters for each pathway to facilitate screening and evaluation of pathway-specific modulators (agonists and/or inhibitors), as well as bioreporters for simultaneous co-activation of both pathways, thereby empowering the investigation of synergistic effects of NF-κB and Wnt signaling in cancer chemoresistance and progression.