Stanislav Y. Shvartsman

Contact
stas@princeton.eduResearch Area
Cell Biology, Development & CancerResearch Focus
Dynamics of living tissuesQuantitative Analysis of Development
The main focus of our laboratory is on the quantitative analysis of development. Our goal is to establish truly predictive and multiscale models that connect multiple levels of description, from gene sequence to pattern formation and morphogenesis. We emphasize close coupling between experiments, computations, and theory, and use Drosophila as an experimental system for model validation. Current projects include genome-wide experimental analysis of signal integration in the Drosophila ovary, computational prediction of sequence-specific patterns of gene regulation by multiple extracellular signals, parameter estimation for morphogen gradients, and quantitative analysis of feedback control in pattern formation.
Signaling crosstalk in the drosophila ovary
The dorsoventral patterning of the follicular epithelium in the developing Drosophila egg relies on the joint activity of evolutionarily conserved EGF and BMP signaling pathways. We have carried out a genome-wide screen for common targets of EGF and BMP pathways in the ovary, established the spatial patterns of their expression, and begun to probe the mechanisms for their transcriptional and posttranscriptional regulation. The current challenge is to go beyond simple association of extracellular signals and transcriptional targets and to understand how the spatial patterns of identified genes are established by integration of two extracellular signals.
Quantitative analysis of morphogen gradients
Pattern formation in development depends on quantitative control of the spatial ranges of secreted ligands. At this time, direct measurements of the length scales of morphogen ligands are extremely difficult. We have developed a parameter estimation approach for quantifying the spatial range of Gurken, an EGF-like ligand that acts as a morphogen in patterning of the Drosophila egg. Our approach combines transport modeling and quantitative characterization of targeted gene expression systems in oogenesis. Using this method, we have estimated the magnitude of a dimensionless parameter that controls the Gurken gradient. We are currently extending this approach to analyze the terminal patterning system in the early embryo.
Negative feedback in pattern formation systems
Negative feedbacks are abundant in patterning networks, but both the biochemical basis of feedbacks and their functional significance are poorly understood at this time. Recent experiments in the Lemmon laboratory at UPenn have provided a detailed biochemical characterization of the biochemical action of Argos, an extracellular inhibitor that provides negative feedback for EGFR signaling in Drosophila. We are using this information to understand the mechanism of Argos action in the embryonic ventral ectoderm (VE). We are interested in determining both the spatial range of Argos and its contribution to the robustness in VE patterning.
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Optogenetic Rescue of a Patterning Mutant. Curr Biol. 2020 ;30(17):3414-3424.e3. .
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Publisher Correction: Mechanics of a multilayer epithelium instruct tumour architecture and function. Nature. 2020 ;586(7827):E9. .
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Mechanics of a multilayer epithelium instruct tumour architecture and function. Nature. 2020 ;585(7825):433-439. .
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Chemical Embryology Redux: Metabolic Control of Development. Trends Genet. 2020 ;36(8):577-586. .
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Template-based mapping of dynamic motifs in tissue morphogenesis. PLoS Comput Biol. 2020 ;16(8):e1008049. .
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Excess dNTPs Trigger Oscillatory Surface Flow in the Early Drosophila Embryo. Biophys J. 2020 ;118(10):2349-2353. .
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Rapid Dynamics of Signal-Dependent Transcriptional Repression by Capicua. Dev Cell. 2020 ;52(6):794-801.e4. .
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Inference of Multisite Phosphorylation Rate Constants and Their Modulation by Pathogenic Mutations. Curr Biol. 2020 ;30(5):877-882.e6. .
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Activation-induced substrate engagement in ERK signaling. Mol Biol Cell. 2020 ;31(4):235-243. .
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The design and logic of terminal patterning in Drosophila. Curr Top Dev Biol. 2020 ;137:193-217. .
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Optimizing photoswitchable MEK. Proc Natl Acad Sci U S A. 2019 ;116(51):25756-25763. .
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Self-Similar Dynamics of Nuclear Packing in the Early Drosophila Embryo. Biophys J. 2019 ;117(4):743-750. .
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Functional divergence caused by mutations in an energetic hotspot in ERK2. Proc Natl Acad Sci U S A. 2019 ;116(31):15514-15523. .
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Energy budget of Drosophila embryogenesis. Curr Biol. 2019 ;29(12):R566-R567. .
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Nuclear (Bio)physics in the Embryo. Cell. 2019 ;177(4):799-801. .
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Entropic effects in cell lineage tree packings. Nat Phys. 2018 ;14(10):1016-1021. .
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A quantitative model of developmental RTK signaling. Dev Biol. 2018 ;442(1):80-86. .
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Outstanding questions in developmental ERK signaling. Development. 2018 ;145(14). .
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Spherical Caps in Cell Polarization. Biophys J. 2018 ;115(1):26-30. .
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Collective Growth in a Small Cell Network. Curr Biol. 2017 ;27(17):2670-2676.e4. .
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Synthesizing developmental trajectories. PLoS Comput Biol. 2017 ;13(9):e1005742. .
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Mechanisms and causality in molecular diseases. Hist Philos Life Sci. 2017 ;39(4):35. .
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Complex structures from patterned cell sheets. Philos Trans R Soc Lond B Biol Sci. 2017 ;372(1720). .
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Divergent effects of intrinsically active MEK variants on developmental Ras signaling. Nat Genet. 2017 ;49(3):465-469. .
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The Design Space of the Embryonic Cell Cycle Oscillator. Biophys J. 2017 ;113(3):743-752. .
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How activating mutations affect MEK1 regulation and function. J Biol Chem. 2017 ;292(46):18814-18820. .
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A novel function for the IκB inhibitor Cactus in promoting Dorsal nuclear localization and activity in the embryo. Development. 2017 ;144(16):2907-2913. .
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Dynamic Control of dNTP Synthesis in Early Embryos. Dev Cell. 2017 ;42(3):301-308.e3. .
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Parallel imaging of embryos for quantitative analysis of genetic perturbations of the Ras pathway. Dis Model Mech. 2017 ;10(7):923-929. .
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Gene regulation during eggshell patterning. Proc Natl Acad Sci U S A. 2017 ;114(23):5808-5813. .
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Epithelial Patterning, Morphogenesis, and Evolution: Drosophila Eggshell as a Model. Dev Cell. 2017 ;41(4):337-348. .
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Uncoupling neurogenic gene networks in the embryo. Genes Dev. 2017 ;31(7):634-638. .
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A process engineering approach to increase organoid yield. Development. 2017 ;144(6):1128-1136. .
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The Spatiotemporal Limits of Developmental Erk Signaling. Dev Cell. 2017 ;40(2):185-192. .
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In vivo severity ranking of Ras pathway mutations associated with developmental disorders. Proc Natl Acad Sci U S A. 2017 ;114(3):510-515. .
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Reconstructing ERK Signaling in the Drosophila Embryo from Fixed Images. Methods Mol Biol. 2017 ;1487:337-351. .
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Diffusive flux in a model of stochastically gated oxygen transport in insect respiration. J Chem Phys. 2016 ;144(20):204101. .
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Shape Transformations of Epithelial Shells. Biophys J. 2016 ;110(7):1670-1678. .
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Minibrain and Wings apart control organ growth and tissue patterning through down-regulation of Capicua. Proc Natl Acad Sci U S A. 2016 ;113(38):10583-8. .
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Long-term dynamics of multisite phosphorylation. Mol Biol Cell. 2016 ;27(14):2331-40. .
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Microfluidics for High-Throughput Quantitative Studies of Early Development. Annu Rev Biomed Eng. 2016 ;18:285-309. .
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Dynamics of Inductive ERK Signaling in the Drosophila Embryo. Curr Biol. 2015 ;25(13):1784-90. .
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Diversity of epithelial morphogenesis during eggshell formation in drosophilids. Development. 2015 ;142(11):1971-7. .
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Mapping the binding interface of ERK and transcriptional repressor Capicua using photocrosslinking. Proc Natl Acad Sci U S A. 2015 ;112(28):8590-5. .
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From discrete to continuum models of three-dimensional deformations in epithelial sheets. Biophys J. 2015 ;109(1):154-63. .
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A Systematic Ensemble Approach to Thermodynamic Modeling of Gene Expression from Sequence Data. Cell Syst. 2015 ;1(6):396-407. .
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Structural Basis of Neurohormone Perception by the Receptor Tyrosine Kinase Torso. Mol Cell. 2015 ;60(6):941-52. .
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A Transport Model for Estimating the Time Course of ERK Activation in the C. elegans Germline. Biophys J. 2015 ;109(11):2436-45. .
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Dynamics of gradient formation by intracellular shuttling. J Chem Phys. 2015 ;143(7):074116. .
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RASopathies: unraveling mechanisms with animal models. Dis Model Mech. 2015 ;8(8):769-82. .