Transgenic mouse models provide the possibility to study cancer progression in vivo in a controlled, experimentally manipulable manner. The Myc oncogene is deregulated in a wide range of human cancers, and its activity is often associated with highly aggressive tumor behavior. Myc is a transcription factor that regulates the expression of several thousand genes both directly and through its effects on chromatin structure. Further, Myc is a key factor in induced pluripotency whereby fully differentiated cells can be converted to a pluripotent state by provision of four reprogramming factors (Sox2, Nanog, Oct4, and Myc). Although expression of Myc is required at various stages for correct development of normal hematopoietic lineages, this occurs under strict regulatory constraints. Sustained inappropriate over-expression of Myc leads, in many cases, to tumorigenesis. We have previously studied the ability of Myc to induce tumors in liver, osteosarcoma, and T-cell lymphoma transgenic mouse models. Here, we will focus on analysis of Myc-induced lymphomas, synergistically with our study of human lymphoid and myeloid malignancy. Our mouse model will enable us to analyze induction of self-renewal programs leading to tumor formation, in a controlled context with a specific mechanism of action (Myc over-expression). Using this system, we can also cause tumors to regress and then relapse, permitting analysis of the latter phenomenon and how it relates to cell states. Further, by manipulating genes such as P53, PI 6, Bim inactivation we will perturb processes of apoptosis and senescence to determine their effects on tumor onset and regression.

National Institute of Health (NIH)
National Cancer Institute (NCI)
Specialized Center--Cooperative Agreements (U54)
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Special Emphasis Panel (ZCA1-SRLB-C)
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Stanford University
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Gallaher, Jill; Babu, Aravind; Plevritis, Sylvia et al. (2014) Bridging population and tissue scale tumor dynamics: a new paradigm for understanding differences in tumor growth and metastatic disease. Cancer Res 74:426-35
Bendall, Sean C; Davis, Kara L; Amir, El-Ad David et al. (2014) Single-cell trajectory detection uncovers progression and regulatory coordination in human B cell development. Cell 157:714-25
Sinha, Subarna; Tsang, Emily K; Zeng, Haoyang et al. (2014) Mining TCGA data using Boolean implications. PLoS One 9:e102119
Choi, Peter S; Li, Yulin; Felsher, Dean W (2014) Addiction to multiple oncogenes can be exploited to prevent the emergence of therapeutic resistance. Proc Natl Acad Sci U S A 111:E3316-24
Gaudillière, Brice; Fragiadakis, Gabriela K; Bruggner, Robert V et al. (2014) Clinical recovery from surgery correlates with single-cell immune signatures. Sci Transl Med 6:255ra131
Sen, Nandini; Mukherjee, Gourab; Sen, Adrish et al. (2014) Single-cell mass cytometry analysis of human tonsil T cell remodeling by varicella zoster virus. Cell Rep 8:633-45
Li, Y; Casey, S C; Felsher, D W (2014) Inactivation of MYC reverses tumorigenesis. J Intern Med 276:52-60
Li, Yulin; Choi, Peter S; Casey, Stephanie C et al. (2014) Activation of Cre recombinase alone can induce complete tumor regression. PLoS One 9:e107589
Bruggner, Robert V; Bodenmiller, Bernd; Dill, David L et al. (2014) Automated identification of stratifying signatures in cellular subpopulations. Proc Natl Acad Sci U S A 111:E2770-7
Gevaert, Olivier; Mitchell, Lex A; Achrol, Achal S et al. (2014) Glioblastoma multiforme: exploratory radiogenomic analysis by using quantitative image features. Radiology 273:168-74

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