Martin H. Wühr Position Associate Professor of Molecular Biology and the Lewis-Sigler Institute for Integrative Genomics Website Wuhr Lab Office Phone 609-258-7653 Email [email protected] Assistant Sara Thibeault Office Icahn Laboratory, 246 Bio/Description FocusDevelop and employ quantitative proteomics methods to obtain a systems level understanding of cellular organizationResearchHow do molecules organize into living systems?We now have a near complete parts list of all the molecules constituting cells. However, we still only poorly understand how all these tiny molecules self-organize into much larger organelles, cells, and organisms. Our group aims to elucidate principles underlying this organization. Specifically, we study how the proteome partitions between nucleus and cytoplasm. We aim to decipher the underlying molecular mechanisms, and ask how different nuclear composition affects biological function. To address these questions we employ and develop mass-spectrometry based proteomics and combine this technology with computational, biochemical, and imaging approaches. Our main research models are human tissue culture cells and the eggs, cell-free extracts, and embryos of the frog Xenopus laevis. Selected Publications 1.Zeng X, Xing X, Gupta M, Keber F, Lopez J, Lee Y-C, Roichman A, Wang L, Neinast M, Donia M, Wühr M, Jang C, Rabinowitz J. Gut bacterial nutrient preferences quantified in vivo. Cell. 2022;185(18):3441–3456.e19. PMCID: PMC9450212 1.Nguyen T, Costa E, Deibert T, Reyes J, Keber F, Tomschik M, Stadlmeier M, Gupta M, Kumar C, Cruz E, Amodeo A, Gatlin J, Wühr M. Differential nuclear import sets the timing of protein access to the embryonic genome. Nat Commun. 2022;13(1):5887. PMCID: PMC9537182 1.Schröder H, Stadlmeier M, Wühr M, Link J. The Shuttling Cascade in Lasso Peptide Benenodin-1 is Controlled by Non-Covalent Interactions. Chemistry. 2022;28(5):e202103615. PMCID: PMC8792204 1.Nofal M, Wang T, Yang L, Jankowski C, Li S, Han S, Parsons L, Frese A, Gitai Z, Anthony T, Wühr M, Sabatini D, Rabinowitz J. GCN2 adapts protein synthesis to scavenging-dependent growth. Cell Syst. 2022;13(2):158–172.e9. PMCID: PMC8961722 1.Dai W, Li A, Yu N, Nguyen T, Leach R, Wühr M, Kleiner R. Activity-based RNA-modifying enzyme probing reveals DUS3L-mediated dihydrouridylation. Nat Chem Biol. 2021;17(11):1178–1187. PMCID: PMC8551019 1.Johnson A, Stadlmeier M, Wühr M. TMTpro Complementary Ion Quantification Increases Plexing and Sensitivity for Accurate Multiplexed Proteomics at the MS2 Level. J Proteome Res. 2021;20(6):3043–3052. PMCID: PMC8330405 1.Crapse J, Pappireddi N, Gupta M, Shvartsman S, Wieschaus E, Wühr M. Evaluating the Arrhenius equation for developmental processes. Mol Syst Biol. 2021;17(8):e9895. PMCID: PMC8377445 1.Yeung E, McFann S, Marsh L, Dufresne E, Filippi S, Harrington H, Shvartsman S, Wühr M. Inference of Multisite Phosphorylation Rate Constants and Their Modulation by Pathogenic Mutations. Curr Biol. 2020;30(5):877–882.e6. PMCID: PMC7085240 1.Cao W, Kabelitz S, Gupta M, Yeung E, Lin S, Rammelt C, Ihling C, Pekovic F, Low T, Siddiqui N, Cheng M, Angers S, Smibert C, Wühr M, Wahle E, Lipshitz H. Precise Temporal Regulation of Post-transcriptional Repressors Is Required for an Orderly Drosophila Maternal-to-Zygotic Transition. Cell Rep. 2020;31(12):107783. PMCID: PMC7372737 1.Stadlmeier M, Runtsch L, Streshnev F, Wühr M, Carell T. A Click-Chemistry-Based Enrichable Crosslinker for Structural and Protein Interaction Analysis by Mass Spectrometry. Chembiochem. 2020;21(1-2):103–107. PMCID: PMC6980279 View all publications 1.Li A, Mao D, Yoshimura A, Rosen P, Martin L, Gallant Étienne, Wühr M, Seyedsayamdost M. Multi-Omic Analyses Provide Links between Low-Dose Antibiotic Treatment and Induction of Secondary Metabolism in Burkholderia thailandensis. mBio. 2020;11(1). PMCID: PMC7042699 1.Hart E, Gupta M, Wühr M, Silhavy T. The gain-of-function allele bypasses the essential requirement for BamD in β-barrel outer membrane protein assembly. Proc Natl Acad Sci U S A. 2020;117(31):18737–18743. PMCID: PMC7414184 1.Peshkin L, Gupta M, Ryazanova L, Wühr M. Bayesian Confidence Intervals for Multiplexed Proteomics Integrate Ion-statistics with Peptide Quantification Concordance. Mol Cell Proteomics. 2019;18(10):2108–2120. PMCID: PMC6773559 1.Hart E, Gupta M, Wühr M, Silhavy T. The Synthetic Phenotype of Δ Δ Double Mutants Results from a Lethal Jamming of the Bam Complex by the Lipoprotein RcsF. mBio. 2019;10(3). PMCID: PMC6529638 1.Pappireddi N, Martin L, Wühr M. A Review on Quantitative Multiplexed Proteomics. Chembiochem. 2019;20(10):1210–1224. PMCID: PMC6520187 1.Tye B, Commins N, Ryazanova L, Wühr M, Springer M, Pincus D, Churchman S. Proteotoxicity from aberrant ribosome biogenesis compromises cell fitness. Elife. 2019;8. PMCID: PMC6453566 1.Nguyen T, Pappireddi N, Wühr M. Proteomics of nucleocytoplasmic partitioning. Curr Opin Chem Biol. 2019;48:55–63. PMCID: PMC6382543 1.Nguyen T, Mitchison T, Wühr M. Immunofluorescence of Microtubule Assemblies in Amphibian Oocytes and Early Embryos. Methods Mol Biol. 2019;1920:17–32. PMCID: PMC6582944 1.Stadlmeier M, Bogena J, Wallner M, Wühr M, Carell T. A Sulfoxide-Based Isobaric Labelling Reagent for Accurate Quantitative Mass Spectrometry. Angew Chem Int Ed Engl. 2018;57(11):2958–2962. PMID: 29316131 1.Sonnett M, Yeung E, Wühr M. Accurate, Sensitive, and Precise Multiplexed Proteomics Using the Complement Reporter Ion Cluster. Anal Chem. 2018;90(8):5032–5039. PMCID: PMC6220677 1.Sonnett M, Gupta M, Nguyen T, Wühr M. Quantitative Proteomics for Xenopus Embryos II, Data Analysis. Methods Mol Biol. 2018;1865:195–215. PMCID: PMC6534117 1.Gupta M, Sonnett M, Ryazanova L, Presler M, Wühr M. Quantitative Proteomics of Xenopus Embryos I, Sample Preparation. Methods Mol Biol. 2018;1865:175–194. PMCID: PMC6564683 1.Remillard D, Buckley D, Paulk J, Brien G, Sonnett M, Seo H-S, Dastjerdi S, Wühr M, Dhe-Paganon S, Armstrong S, Bradner J. Degradation of the BAF Complex Factor BRD9 by Heterobifunctional Ligands. Angew Chem Int Ed Engl. 2017;56(21):5738–5743. PMCID: PMC5967236 1.Presler M, Van Itallie E, Klein A, Kunz R, Coughlin M, Peshkin L, Gygi S, Wühr M, Kirschner M. Proteomics of phosphorylation and protein dynamics during fertilization and meiotic exit in the egg. Proc Natl Acad Sci U S A. 2017;114(50):E10838-E10847. PMCID: PMC5740657 1.Hasley A, Chavez S, Danilchik M, Wühr M, Pelegri F. Vertebrate Embryonic Cleavage Pattern Determination. Adv Exp Med Biol. 2017;953:117–171. PMCID: PMC6500441 1.Tassan J-P, Wühr M, Hatte G, Kubiak J. Asymmetries in Cell Division, Cell Size, and Furrowing in the Xenopus laevis Embryo. Results Probl Cell Differ. 2017;61:243–260. PMID: 28409308 1.Pierre A, Sallé J, Wühr M, Minc N. Generic Theoretical Models to Predict Division Patterns of Cleaving Embryos. Dev Cell. 2016;39(6):667–682. PMCID: PMC5180451 1.Wühr M, Güttler T, Peshkin L, McAlister G, Sonnett M, Ishihara K, Groen A, Presler M, Erickson B, Mitchison T, Kirschner M, Gygi S. The Nuclear Proteome of a Vertebrate. Curr Biol. 2015;25(20):2663–71. PMCID: PMC4618192 1.Peshkin L, Wühr M, Pearl E, Haas W, Freeman R, Gerhart J, Klein A, Horb M, Gygi S, Kirschner M. On the Relationship of Protein and mRNA Dynamics in Vertebrate Embryonic Development. Dev Cell. 2015;35(3):383–94. PMCID: PMC4776761 1.McAlister G, Nusinow D, Jedrychowski M, Wühr M, Huttlin E, Erickson B, Rad R, Haas W, Gygi S. MultiNotch MS3 enables accurate, sensitive, and multiplexed detection of differential expression across cancer cell line proteomes. Anal Chem. 2014;86(14):7150–8. PMCID: PMC4215866 1.Wühr M, Freeman R, Presler M, Horb M, Peshkin L, Gygi S, Kirschner M. Deep proteomics of the Xenopus laevis egg using an mRNA-derived reference database. Curr Biol. 2014;24(13):1467–1475. PMCID: PMC4090281 1.Wühr M, Haas W, McAlister G, Peshkin L, Rad R, Kirschner M, Gygi S. Accurate multiplexed proteomics at the MS2 level using the complement reporter ion cluster. Anal Chem. 2012;84(21):9214–21. PMCID: PMC3771681 1.Wühr M, Tan E, Parker S, Detrich W, Mitchison T. A model for cleavage plane determination in early amphibian and fish embryos. Curr Biol. 2010;20(22):2040–5. PMCID: PMC3031131 1.Wühr M, Chen Y, Dumont S, Groen A, Needleman D, Salic A, Mitchison T. Evidence for an upper limit to mitotic spindle length. Curr Biol. 2008;18(16):1256–61. PMCID: PMC2561182 Related News Throwing light on photosynthesis Research Area Biochemistry, Biophysics & Structural Biology Quantitative & Computational Biology