Our MIT CCSB Tumor Cell Networks Center is directed toward achieving three overarching objectives: Objective 1 - Cancer Research: advance the development and application of new systems biology approaches to cancer research in three significant scientific areas (mitogenesis, migration, and DNA damage/repair) and improve corresponding approaches for discovery and use of cancer therapies;Objective 2 - Education: train a new generation of young research leaders comfortable at the interdisciplinary interface between experimental molecular/cell biology and quantitative modeling in key areas of basic and applied cancer research;Objective 3 - Collaboration and Outreach: serve the general cancer biology community by acting as a collaborative partner that brings new ideas and methods to a wide community of investigators regardless of institutional affiliation. A central thread integrating our experiment and modeling efforts is a paradigmatic 'cue-signal-response'framework for probing and modeling the regulation of tumor cell phenotypes critical to tumor cell biology.
We aim to develop and make available to the cancer biology community successful models of three distinct but inter-related classes of models: 'Cell Response'models, capable of predicting how cellular phenotypes are executed by biophysical molecular processes;'Signal-Response'models, capable of predicting how cellular responses are regulated by information carried by intracellular signaling pathways;and 'Cue-Signal'models, capable of predicting what intracellular signals are generated by environmental stimuli and therapeutic agents in the context of specific genotypes. The construction and testing of all three classes of models is currently underway and linked to three important problems in cancer biology and therapy: (a) cancer progression via dysregulation of mitogenic signaling pathways downstream of receptor tyrosine kinases;(b) cancer progression via inappropriate cell migration processes that promote invasive and metastatic behavior;and (c) cancer treatment via molecular pharmaceuticals including chemotherapeutics and targeted inhibitors. Our Education and Outreach activities include participation in regular meetings of a student/postdoc/faculty systems biology community at MIT as well as dedicated seminars and retreats, offering of curricular subjects, short courses, conference sessions, and symposia related to cancer systems biology. We also are proactive in making our data, models, and publications available on our website, and in collaborative interactions with cancer biology investigators at other institutions.
The purpose of the NCI CCSB initiative as stated in RFA-CA-09-011 is: to stimulate the development and apphcation of the integrative systems approaches and mathematical/computational modeling to cancer research... specifically in the areas of (a) cancer biology;(b) experimental therapeutics;(c) early interventions;and (d) cancer susceptibihty. Our MIT CCSB Tumor Cell Networks Center focus will fall centrally within Area (a), cancer biology, with intersection into Area (b), experimental therapeutics.
|Lescarbeau, Rebecca S; Lei, Liang; Bakken, Katrina K et al. (2016) Quantitative Phosphoproteomics Reveals Wee1 Kinase as a Therapeutic Target in a Model of Proneural Glioblastoma. Mol Cancer Ther 15:1332-43|
|Oudin, Madeleine J; Miller, Miles A; Klazen, Joelle A Z et al. (2016) MenaINV mediates synergistic cross-talk between signaling pathways driving chemotaxis and haptotaxis. Mol Biol Cell 27:3085-3094|
|Tape, Christopher J; Ling, Stephanie; Dimitriadi, Maria et al. (2016) Oncogenic KRAS Regulates Tumor Cell Signaling via Stromal Reciprocation. Cell 165:910-20|
|Lescarbeau, Rebecca S; Lei, Liang; Bakken, Katrina K et al. (2016) Quantitative phosphoproteomics reveals Wee1 kinase as a therapeutic target in a model of proneural glioblastoma. Mol Cancer Ther :|
|de Picciotto, Seymour; Dickson, Paige M; Traxlmayr, Michael W et al. (2016) Design Principles for SuCESsFul Biosensors: Specific Fluorophore/Analyte Binding and Minimization of Fluorophore/Scaffold Interactions. J Mol Biol 428:4228-4241|
|Miller, Miles A; Oudin, Madeleine J; Sullivan, Ryan J et al. (2016) Reduced Proteolytic Shedding of Receptor Tyrosine Kinases Is a Post-Translational Mechanism of Kinase Inhibitor Resistance. Cancer Discov 6:382-99|
|Tuncbag, Nurcan; Gosline, Sara J C; Kedaigle, Amanda et al. (2016) Network-Based Interpretation of Diverse High-Throughput Datasets through the Omics Integrator Software Package. PLoS Comput Biol 12:e1004879|
|Carmona, G; Perera, U; Gillett, C et al. (2016) Lamellipodin promotes invasive 3D cancer cell migration via regulated interactions with Ena/VASP and SCAR/WAVE. Oncogene 35:5155-69|
|Reddy, Raven J; Gajadhar, Aaron S; Swenson, Eric J et al. (2016) Early signaling dynamics of the epidermal growth factor receptor. Proc Natl Acad Sci U S A 113:3114-9|
|Oudin, Madeleine J; Jonas, Oliver; Kosciuk, Tatsiana et al. (2016) Tumor Cell-Driven Extracellular Matrix Remodeling Drives Haptotaxis during Metastatic Progression. Cancer Discov 6:516-31|
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