Kevin A. Janes

Education

  • PhD, Massachusetts Institute of Technology, Cambridge, MA
  • BS, Johns Hopkins University, Baltimore, MD
  • Postdoc, Harvard Medical School, Boston, MA

Primary Appointment

  • Associate Professor, Biomedical Engineering

Contact

Research Interest(s)

Systems-biology approaches to cancer biology and virology.

Research Description

Changes in cellular behavior underlie development, disease, and homeostasis. The response of cells to external factors depends upon the synthesis, degradation, and modification of genes and proteins. These regulated events act as "signals" for coordinating cell function. Intracellular signaling is highly dynamic, interconnected, and context dependent, making it difficult to predict how any one signal contributes to the control of cell fate. Understanding how signaling networks enable cells to respond to their environment is important for diseases such as cancer, where the molecular "signal processing" has gone awry and cellular responses are inappropriate.

Our group develops experimental and computational techniques for quantitatively monitoring signaling networks as they become activated by diverse stimuli and perturbations. These tools allow us to collect complex datasets, which can be analyzed by "data-driven" modeling to address network-level questions about signal transduction. Fundamentally, our approach is problem driven, involving techniques that range from enzyme-activity assays in cell populations to gene-expression measurements in individual microdissected cells. We are currently interested in studying the tissue responses of colonic epithelia and the morphogenetic responses of 3D-cultured mammary epithelia in vitro.

Selected Publications

  • Bajikar S, Fuchs C, Roller A, Theis F, Janes K. Parameterizing cell-to-cell regulatory heterogeneities via stochastic transcriptional profiles. Proceedings of the National Academy of Sciences of the United States of America. 2014;111(5): E626-35. PMID: 24449900 | PMCID: PMC3918796
  • Wang C, Bajikar S, Jamal L, Atkins K, Janes K. A time- and matrix-dependent TGFBR3-JUND-KRT5 regulatory circuit in single breast epithelial cells and basal-like premalignancies. Nature cell biology. 2014;16(4): 345-56. PMID: 24658685 | PMCID: PMC4035356
  • Wang L, Janes K. Stochastic profiling of transcriptional regulatory heterogeneities in tissues, tumors and cultured cells. Nature protocols. 2013;8(2): 282-301. PMID: 23306461 | PMCID: PMC3818581
  • Bajikar S, Janes K. Multiscale models of cell signaling. Annals of biomedical engineering. 2012;40(11): 2319-27. PMID: 22476894 | PMCID: PMC3436998
  • Jensen K, Janes K. Modeling the latent dimensions of multivariate signaling datasets. Physical biology. 2012;9(4): 045004. PMID: 22871687 | PMCID: PMC3769421
  • RUNX1 and its understudied role in breast cancer. Cell cycle (Georgetown, Tex.). 2011;10(20): 3461-5. PMID: 22024923 | PMCID: PMC3266176
  • Wang C, Jamal L, Janes K. Normal morphogenesis of epithelial tissues and progression of epithelial tumors. Wiley interdisciplinary reviews. Systems biology and medicine. 2011;4(1): 51-78. PMID: 21898857 | PMCID: PMC3242861
  • Wang L, Brugge J, Janes K. Intersection of FOXO- and RUNX1-mediated gene expression programs in single breast epithelial cells during morphogenesis and tumor progression. Proceedings of the National Academy of Sciences of the United States of America. 2011;108(40): E803-12. PMID: 21873240 | PMCID: PMC3189061
  • Paring down signaling complexity. Nature biotechnology. 2010;28(7): 681-2. PMID: 20622836 | PMCID: PMC3180998
  • Garmaroudi F, Marchant D, Si X, Khalili A, Bashashati A, Wong B, Tabet A, Ng R, Murphy K, Luo H, Janes K, McManus B. Pairwise network mechanisms in the host signaling response to coxsackievirus B3 infection. Proceedings of the National Academy of Sciences of the United States of America. 2010;107(39): 17053-8. PMID: 20833815 | PMCID: PMC2947887
  • Janes K, Wang C, Holmberg K, Cabral K, Brugge J. Identifying single-cell molecular programs by stochastic profiling. Nature methods. 2010;7(4): 311-7. PMID: 20228812 | PMCID: PMC2849806
  • Janes K, Reinhardt H, Yaffe M. Cytokine-induced signaling networks prioritize dynamic range over signal strength. Cell. 2008;135(2): 343-54. PMID: 18957207 | PMCID: PMC2635014