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Llura and Gordon Gund Professor of Neurosciences and of Molecular and Cellular Biology and Professor of Applied Physics and Stem Cell and Regenerative Biology

Sharad Ramanathan

Llura and Gordon Gund Professor of Neurosciences and of Molecular and Cellular Biology and Professor of Applied Physics and Stem Cell and Regenerative Biology

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Our laboratory studies how cells and organisms make decisions. To arrive at a decision, organisms must measure multiple environmental signals and interpret them appropriately. The questions we are interested in are how cells and organisms interpret their environment, how this interpretation depends on prior experiences, as well as the spatial, temporal modulation and the statistics of environmental cues. We want to achieve a quantitative understanding of the underlying signaling and transcriptional circuits that lead to discrete decisions. Since our goal is to uncover general design principles of the circuits that underlie decision making, our lab works on several model systems. Our recent work has focused on the yeast Sacchromyces cerevisiae, but we are now working on circuits that make developmental decisions in mammalian cells and behavioral decisions in the worm C. elegans. We are also developing several new optical and micro-fluidic techniques to interrogate the dynamics of signaling and transcriptional networks in single cells.

Selected Publications

Furchtgott LA, Melton S, Menon V, Ramanathan S. Discovering sparse transcription factor codes for cell states and state transitions during development. eLife; 6:e20488 (2017). 

Jang S, Choubey S, Furchtgott L, Zou LN, Doyle A, Menon V, Loew EB, Krostag AR, Martinez RA, Madisen L, Levi BP, Ramanathan S. Dynamics of embryonic stem cell differentiation inferred from single-cell transcriptomics show a series of transitions through discrete cell states. eLife; 6:e20487 (2017).

Yao, Z., Menon, V., Mich, J.K., Ku, S., Krostag, A., Martinez, R.A., Furchtgott, L., Mulholland, H., Bort, S., Fuqua, M.A., Gregor, B.W., Hodge, R.D., Jayabalu, A., May, R.C., Melton, S., Nelson, A.M., Ngo, N.K., Shapovalova, N.V., Shehata, S.I., Smith, M.W., Tait, L.J., Thomsen, E.R., Ye, C., Glass, I.A., Thompson, C.L., Phillips, J.W., Grimley, J.S., Levi, B.P., Wang, Y., Ramanathan,S., A Single-Cell Roadmap of Lineage Bifurcation in Human ESC Models of Embryonic Brain Development,  Cell Stem Cell  20(1):120-134 (2017). 

Close JL, Yao Z, Levi BP, Miller JA, Bakken TE, Menon V, Ting JT, Wall A, Krostag AR, Thomsen ER, Nelson AM, Mich JK, Hodge RD, Shehata SI, Glass IA, Bort S, Shapovalova NV, Ngo NK, Grimley JS, Phillips JW, Thompson CL, Ramanathan S, Lein E. Single-Cell Profiling of an In Vitro Model of Human Interneuron Development Reveals Temporal Dynamics of Cell Type Production and Maturation. Neuron 93(5):1035-48 (2017). 

Thomsen, E.R., Mich, J.K., Yao, Z., Hodge, R.D., Doyle, A.M., Jang, S., Shehata, S.I., Nelson, A.M., Shapovalova, N.V., Levi, B.P., Ramanathan, S., Fixed single-cell transcriptomic characterization of human radial glial diversity. Nature Methods 13(1) 87093 (2016). 

Kocabas, A.1, Shen, C., Guo, Z.G., Ramanathan, S., Controlling interneuron activity in Caenorhabditis elegans to evoke chemotactic behavior, Nature (2012) 490 273-277

Müller, P., Rogers, K.W., Jordan, B.M., Lee, J.S., Robson, D., Ramanathan, S., Schier, A.F., Differential diffusivity of Nodal and Lefty underlies a reaction-diffusion patterning system. Science (2012) 336 (6082), 721-724.

Thomson, M.W., Liu, S.J., Zou, L.N., Smith, Z., Meissner, A., Ramanathan, S., Pluripotency factors in embryonic stem cells regulate differentiation into germ layers, Cell (2011), 145(6), 875-889

Guo, Z.V., Hart, A.C., Ramanathan, S., Optical interrogation and monitoring of neural circuits in Caenorhabditis elegans, Nature Methods, 6, 891-896 (2009)

Mody A., Weiner J., Ramanathan S., (2009) Modularity of MAP kinases allows deformation of their signaling pathways. Nature Cell Biology 11, 484 – 491

Hersen P., McClean M.N., Mahadevan L., Ramanathan, S., (2008) Signal Processing by the HOG MAP kinase pathway. Proc. Natl. Acad. Sci. USA May 14, 2008, 10.1073/pnas.0710770105

Hallatschek O., Hersen, P., Ramanathan, S., and Nelson, D. (2007) Genetic drift at expanding frontiers promotes gene segregation. Proc. Natl. Acad. Sci. USA 104 (50), 19926-30

Nachman, I., Regev, A., and Ramanathan, S. (2007) Dissecting Timing Variability in Yeast Meiosis. Cell 131, 544-556.

Ramanathan, S., and Broach, J. (2007). Do cells think? Cell. Mol. Life Sci. 64, 1801-4 .

McClean, M. N., Mody, A., Broach, J., and Ramanathan, S. (2007). Decision Making in MAP Kinase pathways. Nat. Genet. 39, 409-414.

Detwiler PB., Ramanathan, S., Sengupta, A., Shraiman BI. (2000). Engineering Aspects of Enzymatic Signal Transduction: Photoreceptors in the Retina. Biophys J, December 2000, p. 2801-2817, Vol. 79, No. 6.