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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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Monitoring the dynamics of the decision making process is the first step towards understanding how developmental and behavioral decisions are made. Measuring the dynamics of complex molecular and neural networks that control these decisions is challenging.

The first direction of our research program has been to develop computational and experimental tools to rapidly identify key nodes within gene regulatory and neural networks whose dynamics control and best reflect the process of decision. The goal is to read the “mind” of the cell or animal as it makes a decision.

The second direction of the program is to monitor the decisions in real time to understand how individual multi-potent cells of the embryo receive and process signals to make developmental decisions, how signal reception and processing is affected by the geometry of the embryo, and how these decisions lead to the patterning of the embryo. These questions are focussed on addressing an open and important question in developmental biology: how the size of tissues and organs and the timing of their development are determined.

The third direction is to exploit our understanding to control the decisions that cells and animals make as well as to re-engineer the underlying networks to produce novel phenotypes. This this end, we want to develop and employ novel bioengineering, microscopy and optogenetic tools. We further exploit the cross species comparisons and analysis to achieve our goal.

Areas of Investigation
• Discovering Key Nodes and Reading Minds of Gene Regulatory Networks
• Signaling and Fate Decisions during early Human and Mouse Development
• Comparative Analysis
• Discovering key nodes in Neural Networks
• Technique Development: Optics and Microfluidics
• Computation, Theory and Modeling

Selected Publications

Zhang, Z. Zwick, S., Loew, E., Grimley, JS, Ramanathan, S. , Mouse embryo geometry drives formation of robust signaling gradients through receptor localization, Nature Communications volume 10, Article number: 4516 (2019).

Lee JB, Yonar A2, Hallacy T, Shen CH, Milloz J, Srinivasan J, Kocabas A, Ramanathan S., A compressed sensing framework for efficient dissection of neural circuits, Nat Methods. 2019 Jan;16(1):126-133 (2019).

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.