Overall, the project is designed to (1) add insights as to the biophysical mechanisms that link molecular- and cell-scale variations in the tumor and the microenvironment to the tumor's growth, (2) develop techniques that allow us to readily incorporate cutting-edge experimental measurements into the multi-scale model and thus more quickly determine their impact on overall tumor progression and response to therapy, (3) investigate and quantify the spatiotemporal dynamics of tumor response to therapy, (4) improve the in vivo-in silico development feedback loop that forms the backbone of true integrative modeling, and so (4) push the frontier of multi-scale, integrative cancer modeling. In order to quantify the relationships between complex cancer phenomena at different scales, we harness the advantages of both discrete and continuum modeling approaches by employing hybrid modeling. We implement hybrid, multi-scale algorithms as the next stage of cancer modeling in general, and lymphoma and leukemia modeling in particular. This involves dynamically coupling tumor-scale models and molecular/cell-scale models developed by Cristini, Macklin and coworkers with cell signaling and evolutionary/hereditary models developed by Research Project 2. This also requires integration with state of- the-art intravital time-course measurements of tumor growth, vascularization, and response to chemotherapy by Gambhir and co-workers. These experiments will (1) provide us with first-hand biological data that will shape the model development, (2) provide us with precise measurements of key model parameters that uniquely constrain the modeling framework, (3) provide additional, independent tests for model validation and testing, and (4) provide an opportunity for true integrative modeling, where our first round of investigating the calibrated model leads to follow-up experiments to test new cancer biology hypotheses and improve the multiscale model.

Public Health Relevance

We bring together a team of leading experts in mathematical modeling of cancer and multiple scales (PI Cristini) with a team of cancer biologists with innovative, cutting-edge in vivo tumor imaging methods (PI Gambhir) to conduct integrative modeling, where experiments shape model development, and subsequent simulations generate testable hypotheses for further experiments.

National Institute of Health (NIH)
National Cancer Institute (NCI)
Specialized Center--Cooperative Agreements (U54)
Project #
Application #
Study Section
Special Emphasis Panel (ZCA1-SRLB-9)
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
University of Southern California
Los Angeles
United States
Zip Code
Ng, Chin F; Frieboes, Hermann B (2018) Simulation of Multispecies Desmoplastic Cancer Growth via a Fully Adaptive Non-linear Full Multigrid Algorithm. Front Physiol 9:821
Tipton, Laura; Müller, Christian L; Kurtz, Zachary D et al. (2018) Fungi stabilize connectivity in the lung and skin microbial ecosystems. Microbiome 6:12
Lee, Jung-Rok; Appelmann, Iris; Miething, Cornelius et al. (2018) Longitudinal Multiplexed Measurement of Quantitative Proteomic Signatures in Mouse Lymphoma Models Using Magneto-Nanosensors. Theranostics 8:1389-1398
Lee, Jung-Rok; Chan, Carmel T; Ruderman, Daniel et al. (2017) Longitudinal Monitoring of Antibody Responses against Tumor Cells Using Magneto-nanosensors with a Nanoliter of Blood. Nano Lett 17:6644-6652
Yan, Huaming; Romero-Lopez, Monica; Frieboes, Hermann B et al. (2017) Multiscale Modeling of Glioblastoma Suggests that the Partial Disruption of Vessel/Cancer Stem Cell Crosstalk Can Promote Tumor Regression Without Increasing Invasiveness. IEEE Trans Biomed Eng 64:538-548
Yan, Huaming; Romero-López, Mónica; Benitez, Lesly I et al. (2017) 3D Mathematical Modeling of Glioblastoma Suggests That Transdifferentiated Vascular Endothelial Cells Mediate Resistance to Current Standard-of-Care Therapy. Cancer Res 77:4171-4184
Tennill, Thomas A; Gross, Mitchell E; Frieboes, Hermann B (2017) Automated analysis of co-localized protein expression in histologic sections of prostate cancer. PLoS One 12:e0178362
Ware, Matthew J; Curtis, Louis T; Wu, Min et al. (2017) Pancreatic adenocarcinoma response to chemotherapy enhanced with non-invasive radio frequency evaluated via an integrated experimental/computational approach. Sci Rep 7:3437
Ng, Chin F; Frieboes, Hermann B (2017) Model of vascular desmoplastic multispecies tumor growth. J Theor Biol 430:245-282
Garvey, Colleen M; Gerhart, Torin A; Mumenthaler, Shannon M (2017) Discrimination and Characterization of Heterocellular Populations Using Quantitative Imaging Techniques. J Vis Exp :

Showing the most recent 10 out of 128 publications