Machine learning was applied for the automated derivation of causal influences in cellular signaling networks. This derivation relied on the simultaneous measurement of multiple phosphorylated protein and phospholipid components in thousands of individual primary human immune system cells. Perturbing these cells with molecular interventions drove the… (More)
Altered growth factor responses in phospho-protein-driven signaling networks are crucial to cancer cell survival and pathology. Profiles of cancer cell signaling networks might therefore identify mechanisms by which such cells interpret environmental cues for continued growth. Using multiparameter flow cytometry, we monitored phospho-protein responses to… (More)
MYC overexpression has been implicated in the pathogenesis of most types of human cancers. MYC is likely to contribute to tumorigenesis by its effects on global gene expression. Previously, we have shown that the loss of MYC overexpression is sufficient to reverse tumorigenesis. Here, we show that there is a precise threshold level of MYC expression… (More)
Statins are a class of drugs that inhibit 3-hydroxy-3-methylglutaryl-coenzyme A (HMGcoA) reductase, a critical enzyme in the mevalonate pathway. Several reports document that statins may prevent different human cancers. However, whether or not statins can prevent cancer is controversial due to discordant results. One possible explanation for these… (More)
BACKGROUND Leukocyte Function Antigen-1 (LFA-1) is a primary adhesion molecule that plays important roles in T cell activation, leukocyte recirculation, and trans-endothelial migration. By applying a multivariate intracellular phospho-proteomic analysis, we demonstrate that LFA-1 differentially activates signaling molecules. RESULTS Signal intensity was… (More)
(1930 articles) Signal Transduction (795 articles) Oncogenes and Tumor Suppressors (4217 articles) Neoplasia Articles on similar topics can be found in the following Blood collections Information about subscriptions and ASH membership may be found online at: digital object identifier (DOIs) and date of initial publication. the indexed by PubMed from initial… (More)
scenario is akin to the magnetic furnace model proposed by Axford and McKenzie (14–16) and to ideas invoking reconnection of mesoscale loops (38, 39). We adopt from the furnace model the idea that reconnection plays a major role, as it will release plasma, set free magnetic energy, and produce Alfvén waves. However, our model of the nascent solar wind is… (More)
We perform network inference ('reverse-engineering') on phospho-specific multi-dimensional flow cytometry measurements of signaling molecules in human T cells using Bayesian networks. Inferred networks are found to have good agreement with known pathways derived from the literature.