Project 3: Integrative computational modeling of tumor-mediated immunosuppression
We will develop and apply computational tools to integrate the complex datasets generated by our Center in order to identify candidate mediators of tumor-immune interactions that induce immunosuppression for functional validation. To enrich our ability for interpretation, we will explore signatures of the immune system in a pan-cancer analysis using the TCGA datasets annotated with time to distant metastasis, in the context of node-negative and nodepositive patients. We hypothesize that pan-cancer genes whose expression is strongly associated with time to distant metastasis are more likely to be associated with tumor-intrinsic or microenvironmental processes driving metastasis progression, thus we will prioritize these genes in our integrative computational analysis of our melanoma and head and neck squamous cell carcinoma datasets. Using the RNAseq data generated by our study, we will develop and apply novel network-based computational methods for reconstructing the interactions between malignant and immune subpopulations. Moreover, we will develop and apply new approaches to integrate the spatial information from high dimensional single cell in situ images from Project 2 with the gene expression datasets to further refine our inferences of candidate mediators of immunosuppression. The datasets and computational resources developed by our Project, and Center at large, will not only enable use to deeply explore the role of lymph nodes in tumor-mediated immunosuppression, but will also provide the community with powerful resources for understanding systemic influences on the forces governing metastatic dissemination.
Sylvia Plevritis, PhD
Sylvia Plevritis, Ph.D. is a Professor in the Department of Radiology in the Stanford School of Medicine. Dr. Plevritis holds a PhD in Electrical Engineering (Stanford, 1992) with concentration on MRI spectroscopic imaging of tumors. She also holds an MS in Health Services Research (Stanford, 1996), with concentration on the evaluation of cancer screening programs on reducing cancer mortality. Dr. Plevritis is the Director of the Stanford Center for Cancer Systems Biology (CCSB), Director of the Cancer Systems Biology Scholars (CSBS) Program, and the co-Section Chief of the Integrative Biomedical Imaging Informatics at Stanford (IBIIS). She has developed integrative cancer research programs that bridge genomics, imaging and population sciences to understand cancer progression and treatment response. She served as PI in the NCI Integrative Cancer Biology Program for the past 10 years, currently as the Director of the Stanford Center in Cancer Systems Biology (CCSB).
Dr. Plevritis is also Director of the Stanford Postdoctoral Scholars Program in Cancer Systems Biology which aims to train the next generation of scholars at the interface of molecular cancer biology and biocomputation. She serves as the coDirector of Integrative Biomedical Imaging Informatics at Stanford (IBIIS, ibiis.stanford.edu), a section in the Department of Radiology that promotes the development and application of novel biocomputational tools to integrate imaging, molecular and clinical data. She has been a Principal Investigator with the NCI Cancer Intervention Surveillance Network (CISNET, cisnet.cancer.gov) for over fifteen years and currently serves on the Executive Committee of Stanford Biomedical Data Sciences Initiative which promotes interdisciplinary research opportunities for “big data” sciences in precision medicine at Stanford University. Having pursued a career path that spans multiple disciplines, she was drawn to cancer systems biology research as it propels the intersection of diverse scientific concepts with the goal of unraveling the complexity of cancer and ultimately defeating this disease through improvements in early detection and treatment strategies.