The goal of this AREA research project is to investigate the effects of various chemical gradients on prostate cancer cell migration and the involved mechanisms using an enabling microfluidic platform in order to elucidate the mechanisms of prostate cancer cells in the bone metastasis.
Two specific aims are proposed including: (1) Develop and characterize microfluidic devices to create repeatable and controllable gradients in micro channels which are arrayed in a parallel fashion under the same field of view of a videoscope in order to test gradient effects of multiple chemicals simultaneously. Using the microfluidic devices, Investigate the effects of chemokine gradients on prostate cancer cell migration and the involved molecular mechanisms to fill the gap of our knowledge in bone metastasis of prostate cancer that can serve a ultimate goal of discovering potential target(s) for cancer therapy. (2) Investigate deformation and related mechanisms of prostate cancer cells during migration using the microfluidic platforms in order to understand how cells migrate through bone microgaps. This research project will help to answer key questions about bone metastases due to prostate cancer cell migration toward chemokine gradients, with experiments enabled by the new arrayed 3-D microfluidic platform. While investigating the proposed research topics, the multidisciplinary collaboration between electrical engineering and biochemistry targeting clinical medicine issues provides a unique academic training to students. Working with prostate cancer cell biologists at Jean H. and John T. Walter, Jr., Center for Research in Urologic Oncology, the integrated, complex yet practical knowledge gained in the team will inspire creative perspectives to establish a foundation for further participation in NIH programs since our institute has not been a major recipient of NIH support, and encourage students to pursue advanced study and potential career paths in the health-related fields. Innovation: The novel aspects of this work lie in the 3-D microfluidic platform enabling in-parallel simultaneous experiments for various chemokines and gradients as well as the finding about the effects of chemical gradients on prostate cancer cell migration and invasion. The microfluidic platform enables multiple simultaneous gradient experiments, increases gradient resolution for accurate studies, provides controllable environments, reduces chemical amount and costs, reduces manual labor and enables ability to study cell deformation for related invasion mechanisms. The effects of chemical gradients on prostate cancer migration will be of interest to understand bone metastases and the potential therapy methods.
A microfluidic platform to study the effects of chemokine gradients on prostate cancer cell migration and deformation. This research project responds to the requests for the Academic Research Enhancement Award (AREA) program to stimulate biomedical research activities at our university, which has not been a major recipient of NIH support. To reach the goal, we propose to investigate the effects of various chemical gradients on prostate cancer cell migration and the involved mechanisms using an enabling microfluidic platform in order to elucidate the mechanisms of prostate cancer cells in the bone metastasis.
The research aims will develop an innovative microfluidic platform for high throughput cell experiments and answer key questions about prostate cancer cell migration and deformation by the effects of chemokine gradients. Through multidisciplinary collaboration between electrical engineering and biochemistry to study clinical medicine problems with consultation by prostate cancer cell biologists at the Center for Research in Urologic Oncology, UT-Southwestern Medical Center, we aim to provide a unique academic training to graduate and undergraduate students and to establish a foundation for further participation in NIH programs in the future.
