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Microfluidic Isolation and Deep Learning-based Profiling of Subtypes of Circulating Tumor Cells during Epithelial Mesenchymal Transition

open

NCI - National Cancer Institute

Title: Microfluidic Isolation and Deep Learning-based Profiling of Subtypes of Circulating Tumor Cells during Epithelial Mesenchymal Transition Project Summary/Abstract Circulating tumor cells (CTCs) are highly heterogeneous and contain many cellular subpopulations. It is known that specific CTC subpopulations, rather than the whole, are responsible for cancer metastases. Recently, epithelial mesenchymal transition (EMT) of adherent epithelial cells to a migratory mesenchymal state has been implicated in tumor metastasis. CTCs isolated from cancer patients exhibit dynamic changes in epithelial and mesenchymal composition, and serial CTC monitoring in those patients suggested an association of EMT in CTCs. Emerging microfluidic technologies have shown great promise for the complete capture of the CTCs population with high yield and enhanced purity. However, most existing devices simply isolate all CTCs in blood without resolving them into distinct subpopulations: isolation of CTC populations with specific EMT markers remains a significant challenge. Consequently, epithelial-mesenchymal plasticity of CTCs during cancer progression is largely unknown, preventing researchers from acquiring true insights into the metastatic potential of CTCs. In the R15 project, we propose to develop the HU microchip platform for isolation and profiling of CTCs in pre-clinical settings, with the focus on detecting and understanding features associated with CTC subtypes during the course (or intermediate states) of EMT. To do so, we will isolate CTCs and explore deep learningbased profiling platforms using both micro and nanometer-scale features found from microscope images obtained from our HU microfluidic devices. This is expected to achieve super-high accuracy for profiling CTC subtypes with varied cell plasticity (i.e., more “epithelial” or more “mesenchymal” type). Building on the success of this project, we expect to develop an integrated system comprising 1) a user-friendly HU microchip for highly efficient isolation of CTCs from blood samples, and 2) an AI-based image analysis platform that can identify CTC subtypes for monitoring cancer progression and support cancer diagnosis and treatment. CTCs with defined EMT stages generated from the NSG mouse model will used to provide critical ground-truth information for validation of the proposed AI model, which cannot be accomplished using other alterative models. This project is strongly integrated with an educational plan to expose undergraduates to advanced experiments in the areas of biomedical engineering and cancer research. It is our belief that involving all students in cutting-edge research will have a significant positive impact on attracting and retaining students in science and healthcare fields. In this grant, we will provide research opportunities for 6 undergraduate students and 1 graduate to learn advanced knowledge on cancer biology, obtain hands-on experience in microfabrication and biological assays. Texas Tech University (TTU) is located in Lubbock, a rural area in northwestern Texas and TTU has been classified as "Tier 1" status in 2016. Due to historical and geographical reasons, life sciences research is not a strength for TTU, and TTU is not a recipient of major NIH grants. This R15 grant will strengthen our research and training at TTU and help us to reach our goal to be one of the best bioengineering programs in Texas.

Up to $607K
2029-05-31
health research

Free to search & build · $99 one-time to unlock the application pack · No subscription

Multilevel, Faith-based Intervention to Promote Rural Physical Activity

open

NCI - National Cancer Institute

PROJECT SUMMARY/ABSTRACT The long-term objective of this K99/R00 application is to develop Dr. Kelsey Day’s ability to become a leader in community-based physical activity research and cancer prevention, particularly through the development of sustainable, multilevel, and participatory solutions. In the K99 phase of the project, Dr. Day will receive support in meeting four training objectives that will facilitate her transition to an independent investigator and expand her knowledge in key content areas that are highly relevant to her long-term career goals. First, she will expand her knowledge of text message and mHealth intervention approaches to increasing physical activity. Second, she will learn how to analyze objective device-measured physical activity data. Third, she will gain theoretical and practical knowledge of community based participatory research methodology. Finally, Dr. Day will obtain advanced training in qualitative research methods. In the K99 phase, Dr. Day will also initiate the research aims of a multilevel, faith-based project focused on physical activity. In Aim 1, she will use a participatory design process to convene focus groups of rural church members to adapt a rural physical activity text message intervention with spiritual content and tailored physical activity feedback. Concurrently, in Aim 2, she will conduct workshops with leaders from rural churches who are paired with a leader from their local Parks and Recreation departments to: 1) establish partnerships; 2) use a participatory approach to adapt evidence-based intervention strategies to increase physical activity; 3) determine barriers and facilitators to the selected strategies within the church/Parks partnership. In Aim 3 (R00 phase), Dr. Day will deliver the multilevel intervention (individual text message intervention, plus church/Parks strategies) to a pilot group of rural churches to evaluate feasibility indicators, including: limited efficacy (changes in Fitbit-measured physical activity among rural churchgoers); acceptability; implementation; and demand. The proposed research seeks to address critical rural health disparities and to promote rural cancer prevention by increasing physical activity opportunities and capacity through a sustainable, multilevel approach. The project is consistent with the NCI’s mission of conducting cancer research that helps individuals across the country live longer and healthier lives, as well as the NCI’s strategic focus on rural cancer disparities. Dr. Day proposes to pursue these training objectives and begin the proposed research aims with the support of the University of Virginia Comprehensive Cancer Center and the Department of Public Health Sciences in the University of Virginia School of Medicine. This environment offers an optimal setting, including research support and resources, to assist her in reaching her training and research objectives.

Up to $115K
2028-04-30
health research

Free to search & build · $99 one-time to unlock the application pack · No subscription

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