Abstract

Public Health Relevance

Aberrant Ras signaling is a fundamental molecular lesion in many human cancers, but Ras proteins are widely regarded as undruggable. For this reason, attention has turned toward developing agents that target downstream kinase cascades such as Ral- GDS, Raf/MEK/ERK, and PI3 kinas/Akt/mTOR. Recent studies in our laboratories and by other groups have uncovered unexpected complexity and heterogeneity in these downstream signaling networks. Our goal is to bring together computational techniques from physical sciences with cancer biology to understand normal Ras-regulated signaling networks and characterize how these networks are remodeled and modulated in cancer. Our studies using T cell leukemia/lymphoma as a model for cancer in general should provide a framework for future preclinical and clinical trials aimed at improving survival while minimizing therapy-related toxicities.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Specialized Center--Cooperative Agreements (U54)
Project #
1U54CA143874-01
Application #
7826002
Study Section
Special Emphasis Panel (ZCA1-SRLB-9 (O1))
Project Start
2009-09-23
Project End
2014-07-31
Budget Start
2009-09-28
Budget End
2010-07-31
Support Year
1
Fiscal Year
2009
Total Cost
$418,399
Indirect Cost

  Institution

Name
Massachusetts Institute of Technology
Department
Type
DUNS #
001425594
City
Cambridge
State
MA
Country
United States
Zip Code
02139

  Publications

Stockslager, Max A; Bagnall, Josephine Shaw; Hecht, Vivian C et al. (2017) Microfluidic platform for characterizing TCR-pMHC interactions. Biomicrofluidics 11:064103
Chen, Xu; Wu, Qiuxia; Depeille, Philippe et al. (2017) RasGRP3 Mediates MAPK Pathway Activation in GNAQ Mutant Uveal Melanoma. Cancer Cell 31:685-696.e6
Stevens, Mark M; Maire, Cecile L; Chou, Nigel et al. (2016) Drug sensitivity of single cancer cells is predicted by changes in mass accumulation rate. Nat Biotechnol 34:1161-1167
Akutagawa, J; Huang, T Q; Epstein, I et al. (2016) Targeting the PI3K/Akt pathway in murine MDS/MPN driven by hyperactive Ras. Leukemia 30:1335-43
Cermak, Nathan; Olcum, Selim; Delgado, Francisco Feijó et al. (2016) High-throughput measurement of single-cell growth rates using serial microfluidic mass sensor arrays. Nat Biotechnol 34:1052-1059
Shaw Bagnall, Josephine; Byun, Sangwon; Miyamoto, David T et al. (2016) Deformability-based cell selection with downstream immunofluorescence analysis. Integr Biol (Camb) 8:654-64
Ramanan, Vyas; Trehan, Kartik; Ong, Mei-Lyn et al. (2016) Viral genome imaging of hepatitis C virus to probe heterogeneous viral infection and responses to antiviral therapies. Virology 494:236-47
McFarland, Christopher D (2016) A modified ziggurat algorithm for generating exponentially- and normally-distributed pseudorandom numbers. J Stat Comput Simul 86:1281-1294
Hosios, Aaron M; Hecht, Vivian C; Danai, Laura V et al. (2016) Amino Acids Rather than Glucose Account for the Majority of Cell Mass in Proliferating Mammalian Cells. Dev Cell 36:540-9
Ksionda, O; Melton, A A; Bache, J et al. (2016) RasGRP1 overexpression in T-ALL increases basal nucleotide exchange on Ras rendering the Ras/PI3K/Akt pathway responsive to protumorigenic cytokines. Oncogene 35:3658-68

Showing the most recent 10 out of 84 publications