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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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Research

Our laboratory studies how multi-potent human cells make developmental decisions and how the nervous system makes behavioral decisions.

We ask how multi-potent cells receive and process signals to build correctly patterned complex tissues of the correct size. Further, we ask how the underlying signaling pathways and gene regulatory networks evolve to produce novel cell types and whether we can take advantage of this evolutionary history to re-engineer these networks. Our final goal is to demonstrate our understanding by patterning and building complex tissues. Our experiments focus on early human development.

We ask how nervous systems process environmental signals to determine animal behavior. We aim to dissect the nervous system to identify key nodes in the network and demonstrate our understanding by taking control of the animal’s behavior by directly manipulating neural activity. Our experimental focus is on the nervous system of the nematode C. elegans.

We bring together developmental, molecular, cell, computational, and neuro-biologists, and bioengineers to achieve our goals.

Selected Publications

Anand GM, Megale HC, Murphy SH, Weis T, Lin Z, He Y, Wang X, Liu J, Ramanathan S. 2023. Controlling organoid symmetry breaking uncovers an excitable system underlying human axial elongation. Cell. 186(3):497-512.e23. PUBMED: 36657443 DOI:S0092-8674(22)01586-0 MCB News

Yaman YI, Ramanathan S. 2023. Controlling human organoid symmetry breaking reveals signaling gradients drive segmentation clock waves. Cell. 186(3):513-527.e19. PUBMED: 36657441 DOI:S0092-8674(22)01585-9 MCB News

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.