The overall goal of this U54 application is to create and support a highly multidisciplinary team of expert oncologists, biologists, biochemists, engineers and both theoretical and experimental physicists. This team will form a Physical Science-Oncology Center (PS-OC) at the Massachusetts Institute of Technology for Single-Cell Dynamics in Cancer (SCDC). The overarching goal of this team is to use both theoretical and experimental approaches inspired by Physics and Engineering to attack important problems in cancer biology by developing novel technology and analytical/computational methods to track the dynamics of cancer at the single cell level. Most investigators from our team are affiliated with institutes in the Boston area including MIT, the Whitehead Institute for Biomedical Research, the Broad Institute of MIT and Harvard, Harvard Medical School, Brigham and Women's Hospital, and Boston University. Institutions from several other investigators are located at the West coast including the University of California, San Francisco and Stanford University. One of team members is located at the Hubrecht Institute and University Medical Center Utrecht in the Netherlands. The SCDC PS-OC will be based on close collaborations between investigators originating from three fields: cancer biology, experimental physics/engineering and theoretical/computational physics. In Project 1 single-cell transcript counting will be use to develop quantitative models of stem cell differentiation and reprogramming in healthy tissue and cancer. Project 2 utilizes complementary in silico, in vitro, and in vivo studies to deconvolute Ras signaling networks in T cell lymphoma. Project 3 will explore the coordination of cell growth and division in normal and cancer cells and Project 4 focuses on characterizing the load of driver and passenger mutations in cancer by modeling neoplastic progression and analyzing genomic data. All projects will make extensive of the Single-Cell Transcript Counting Core and the Cell Sorting and Physical Measurement Core. These facilities and all reagents generated by the cores will be made available to other PS-OCs.

Public Health Relevance

The experimental data and theoretical/computational models generated by this PS-OC will be used to better understand how regulatory networks are altered when a cell undergoes malignant transformation leading to cancer. It is anticipated that these advances will significantly advance medical science and treatment of cancer.

National Institute of Health (NIH)
National Cancer Institute (NCI)
Specialized Center--Cooperative Agreements (U54)
Project #
Application #
Study Section
Special Emphasis Panel (ZCA1-SRLB-9 (O1))
Program Officer
Kuhn, Nastaran Z
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Massachusetts Institute of Technology
Internal Medicine/Medicine
Schools of Arts and Sciences
United States
Zip Code
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
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
Kimmerling, Robert J; Lee Szeto, Gregory; Li, Jennifer W et al. (2016) A microfluidic platform enabling single-cell RNA-seq of multigenerational lineages. Nat Commun 7:10220
Hecht, Vivian C; Sullivan, Lucas B; Kimmerling, Robert J et al. (2016) Biophysical changes reduce energetic demand in growth factor-deprived lymphocytes. J Cell Biol 212:439-47
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

Showing the most recent 10 out of 84 publications