Orion Weiner, PhD
Professor
Cardiovascular Research Inst
School of Medicine

1. How do cells control their shape and movement? 2. How lymphocytes detect rare foreign peptides in a sea of self-peptides? 3. How do cells regulate transcriptional activation?

We study a diversity of cell types and behaviors. We believe that this makes it easier to identify the general principles of cellular decision-making. We often pair biosensors to visualize a quantitative dynamic of choice inside living cells with precision tools to control the regulators of these behaviors. This approach reveals the molecular logic of these complex cell decisions. Transformative science often happens at interfaces. So we seek to borrow tools and concepts from other fields to address open questions in cell biology and frequently develop new tools when they are needed to accelerate progress. Our approach opens up opportunities for cross pollination between different projects in the lab.

• Early-life stress triggers long-lasting organismal resilience and longevity via tetraspanin.
  Science advances 2024 Jiang WI, De Belly H, Wang B, Wong A, Kim M, Oh F, DeGeorge J, Huang X, Guang S, Weiner OD, Ma DK
• Early-life stress triggers long-lasting organismal resilience and longevity via tetraspanin.
  bioRxiv : the preprint server for biology 2023 Jiang WI, De Belly H, Wang B, Wong A, Kim M, Oh F, DeGeorge J, Huang X, Guang S, Weiner OD, Ma DK
• Optogenetic control of YAP reveals a dynamic communication code for stem cell fate and proliferation.
  Nature communications 2023 Meyer K, Lammers NC, Bugaj LJ, Garcia HG, Weiner OD
• Local negative feedback of Rac activity at the leading edge underlies a pilot pseudopod-like program for amoeboid cell guidance.
  PLoS biology 2023 Town JP, Weiner OD
• Plasma membrane abundance dictates phagocytic capacity and functional crosstalk in myeloid cells.
  bioRxiv : the preprint server for biology 2023 Winer BY, Settle AH, Yakimov AM, Jeronimo C, Lazarov T, Tipping M, Saoi M, Sawh A, Sepp AL, Galiano M, Wong YY, Perry JSA, Geissmann F, Cross J, Zhou T, Kam LC, Pasoli HA, Hohl T, Cyster JG, Weiner OD…
• Molecular mechanism of GPCR spatial organization at the plasma membrane.
  Nature chemical biology 2023 Kockelkoren G, Lauritsen L, Shuttle CG, Kazepidou E, Vonkova I, Zhang Y, Breuer A, Kennard C, Brunetti RM, D'Este E, Weiner OD, Uline M, Stamou D
• Neutrophils actively swell to potentiate rapid migration.
  bioRxiv : the preprint server for biology 2023 Nagy TL, Strickland E, Weiner OD
• Self-extinguishing relay waves enable homeostatic control of human neutrophil swarming.
  bioRxiv : the preprint server for biology 2023 Strickland E, Pan D, Godfrey C, Kim JS, Hopke A, Degrange M, Villavicencio B, Mansour MK, Zerbe CS, Irimia D, Amir A, Weiner OD
• Cell protrusions and contractions generate long-range membrane tension propagation.
  Cell 2023 De Belly H, Yan S, Borja da Rocha H, Ichbiah S, Town JP, Zager PJ, Estrada DC, Meyer K, Turlier H, Bustamante C, Weiner OD
• Mechanosensitive mTORC2 independently coordinates leading and trailing edge polarity programs during neutrophil migration.
  Molecular biology of the cell 2023 Saha S, Town JP, Weiner OD
• From peptides to proteins: coiled-coil tetramers to single-chain 4-helix bundles.
  Chemical science 2022 Naudin EA, Albanese KI, Smith AJ, Mylemans B, Baker EG, Weiner OD, Andrews DM, Tigue N, Savery NJ, Woolfson DN
• Progressive enhancement of kinetic proofreading in T cell antigen discrimination from receptor activation to DAG generation.
  eLife 2022 Britain DM, Town JP, Weiner OD
• WASP integrates substrate topology and cell polarity to guide neutrophil migration.
  The Journal of cell biology 2021 Brunetti RM, Kockelkoren G, Raghavan P, Bell GRR, Britain D, Puri N, Collins SR, Leonetti MD, Stamou D, Weiner OD
• The WAVE complex associates with sites of saddle membrane curvature.
  The Journal of cell biology 2021 Pipathsouk A, Brunetti RM, Town JP, Graziano BR, Breuer A, Pellett PA, Marchuk K, Tran NT, Krummel MF, Stamou D, Weiner OD
• Optogenetic Tuning of Protein-protein Binding in Bilayers Using LOVTRAP.
  Bio-protocol 2020 Tischer D, Weiner OD
• Cell confinement reveals a branched-actin independent circuit for neutrophil polarity.
  PLoS biology 2019 Graziano BR, Town JP, Sitarska E, Nagy TL, Fošnaric M, Penic S, Iglic A, Kralj-Iglic V, Gov NS, Diz-Muñoz A, Weiner OD
• Multiple sources of signal amplification within the B-cell Ras/MAPK pathway.
  Molecular biology of the cell 2019 Mclaurin JD, Weiner OD
• A size-invariant bud-duration timer enables robustness in yeast cell size control.
  PloS one 2018 Allard CAH, Decker F, Weiner OD, Toettcher JE, Graziano BR
• Nodal signaling has dual roles in fate specification and directed migration during germ layer segregation in zebrafish.
  Development (Cambridge, England) 2018 Liu Z, Woo S, Weiner OD
• In pursuit of the mechanics that shape cell surfaces.
  Nature physics 2018 Diz-Muñoz A, Weiner OD, Fletcher DA
• Joining forces: crosstalk between biochemical signalling and physical forces orchestrates cellular polarity and dynamics.
  Philosophical transactions of the Royal Society of London. Series B, Biological sciences 2018 Saha S, Nagy TL, Weiner OD
• Chick cranial neural crest cells use progressive polarity refinement, not contact inhibition of locomotion, to guide their migration.
  Developmental biology 2018 Genuth MA, Allen CDC, Mikawa T, Weiner OD
• Clathrin Assembly Defines the Onset and Geometry of Cortical Patterning.
  Developmental cell 2017 Yang Y, Xiong D, Pipathsouk A, Weiner OD, Wu M
• A module for Rac temporal signal integration revealed with optogenetics.
  The Journal of cell biology 2017 Graziano BR, Gong D, Anderson KE, Pipathsouk A, Goldberg AR, Weiner OD
• TAEL: a zebrafish-optimized optogenetic gene expression system with fine spatial and temporal control.
  Development (Cambridge, England) 2016 Reade A, Motta-Mena LB, Gardner KH, Stainier DY, Weiner OD, Woo S
• Positioning the cleavage furrow: All you need is Rho.
  The Journal of cell biology 2016 Liu Z, Weiner OD
• Membrane Tension Acts Through PLD2 and mTORC2 to Limit Actin Network Assembly During Neutrophil Migration.
  PLoS biology 2016 Diz-Muñoz A, Thurley K, Chintamen S, Altschuler SJ, Wu LF, Fletcher DA, Weiner OD
• Gβ Regulates Coupling between Actin Oscillators for Cell Polarity and Directional Migration.
  PLoS biology 2016 Hoeller O, Toettcher JE, Cai H, Sun Y, Huang CH, Freyre M, Zhao M, Devreotes PN, Weiner OD
• Reversible Optogenetic Control of Subcellular Protein Localization in a Live Vertebrate Embryo.
  Developmental cell 2016 Buckley CE, Moore RE, Reade A, Goldberg AR, Weiner OD, Clarke JDW
• Cell Migration: Recoiling from an Embrace.
  Current biology : CB 2015 Genuth MA, Weiner OD
• A naturally monomeric infrared fluorescent protein for protein labeling in vivo.
  Nature methods 2015 Yu D, Baird MA, Allen JR, Howe ES, Klassen MP, Reade A, Makhijani K, Song Y, Liu S, Murthy Z, Zhang SQ, Weiner OD, Kornberg TB, Jan YN, Davidson MW, Shu X
• Probing Yeast Polarity with Acute, Reversible, Optogenetic Inhibition of Protein Function.
  ACS synthetic biology 2015 Jost AP, Weiner OD
• Myosin light chain kinase regulates cell polarization independently of membrane tension or Rho kinase.
  The Journal of cell biology 2015 Lou SS, Diz-Muñoz A, Weiner OD, Fletcher DA, Theriot JA
• Homer3 regulates the establishment of neutrophil polarity.
  Molecular biology of the cell 2015 Wu J, Pipathsouk A, Keizer-Gunnink A, Fusetti F, Alkema W, Liu S, Altschuler S, Wu L, Kortholt A, Weiner OD
• Illuminating cell signalling with optogenetic tools.
  Nature reviews. Molecular cell biology 2014 Tischer D, Weiner OD
• Self-organization of protrusions and polarity during eukaryotic chemotaxis.
  Current opinion in cell biology 2014 Graziano BR, Weiner OD
• Response to Bell et al.
  Molecular biology of the cell 2014 Weiner O
• Synthetic control of mammalian-cell motility by engineering chemotaxis to an orthogonal bioinert chemical signal.
  Proceedings of the National Academy of Sciences of the United States of America 2014 Park JS, Rhau B, Hermann A, McNally KA, Zhou C, Gong D, Weiner OD, Conklin BR, Onuffer J, Lim WA
• How to understand and outwit adaptation.
  Developmental cell 2014 Hoeller O, Gong D, Weiner OD
• How should we be selecting our graduate students?
  Molecular biology of the cell 2014 Weiner OD
• An optogenetic gene expression system with rapid activation and deactivation kinetics.
  Nature chemical biology 2014 Motta-Mena LB, Reade A, Mallory MJ, Glantz S, Weiner OD, Lynch KW, Gardner KH
• Actin dynamics rapidly reset chemoattractant receptor sensitivity following adaptation in neutrophils.
  Philosophical transactions of the Royal Society of London. Series B, Biological sciences 2013 Dandekar SN, Park JS, Peng GE, Onuffer JJ, Lim WA, Weiner OD
• The symphony of cell movement: how cells orchestrate diverse signals and forces to control migration.
  Current opinion in cell biology 2013 Parent CA, Weiner OD
• Two distinct functions for PI3-kinases in macropinocytosis.
  Journal of cell science 2013 Hoeller O, Bolourani P, Clark J, Stephens LR, Hawkins PT, Weiner OD, Weeks G, Kay RR
• A light-inducible organelle-targeting system for dynamically activating and inactivating signaling in budding yeast.
  Molecular biology of the cell 2013 Yang X, Jost AP, Weiner OD, Tang C
• Identifying network motifs that buffer front-to-back signaling in polarized neutrophils.
  Cell reports 2013 Wang Y, Ku CJ, Zhang ER, Artyukhin AB, Weiner OD, Wu LF, Altschuler SJ
• Use the force: membrane tension as an organizer of cell shape and motility.
  Trends in cell biology 2012 Diz-Muñoz A, Fletcher DA, Weiner OD
• Nodal signaling regulates endodermal cell motility and actin dynamics via Rac1 and Prex1.
  The Journal of cell biology 2012 Woo S, Housley MP, Weiner OD, Stainier DY
• Network crosstalk dynamically changes during neutrophil polarization.
  Cell 2012 Ku CJ, Wang Y, Weiner OD, Altschuler SJ, Wu LF
• Diffusion, capture and recycling of SCAR/WAVE and Arp2/3 complexes observed in cells by single-molecule imaging.
  Journal of cell science 2012 Millius A, Watanabe N, Weiner OD
• Light-based feedback for controlling intracellular signaling dynamics.
  Nature methods 2011 Toettcher JE, Gong D, Lim WA, Weiner OD
• A pharmacological cocktail for arresting actin dynamics in living cells.
  Molecular biology of the cell 2011 Peng GE, Wilson SR, Weiner OD
• Light control of plasma membrane recruitment using the Phy-PIF system.
  Methods in enzymology 2011 Toettcher JE, Gong D, Lim WA, Weiner OD
• The promise of optogenetics in cell biology: interrogating molecular circuits in space and time.
  Nature methods 2010 Toettcher JE, Voigt CA, Weiner OD, Lim WA
• Sequence-dependent sorting of recycling proteins by actin-stabilized endosomal microdomains.
  Cell 2010 Puthenveedu MA, Lauffer B, Temkin P, Vistein R, Carlton P, Thorn K, Taunton J, Weiner OD, Parton RG, von Zastrow M
• Manipulation of neutrophil-like HL-60 cells for the study of directed cell migration.
  Methods in molecular biology (Clifton, N.J.) 2010 Millius A, Weiner OD
• Cell stimulation with optically manipulated microsources.
  Nature methods 2009 Kress H, Park JG, Mejean CO, Forster JD, Park J, Walse SS, Zhang Y, Wu D, Weiner OD, Fahmy TM, Dufresne ER
• Compete globally, bud locally.
  Cell 2009 Houk AR, Millius A, Weiner OD
• Spatiotemporal control of cell signalling using a light-switchable protein interaction.
  Nature 2009 Levskaya A, Weiner OD, Lim WA, Voigt CA
• Neutrophils establish rapid and robust WAVE complex polarity in an actin-dependent fashion.
  Current biology : CB 2009 Millius A, Dandekar SN, Houk AR, Weiner OD
• Chemotaxis in neutrophil-like HL-60 cells.
  Methods in molecular biology (Clifton, N.J.) 2009 Millius A, Weiner OD
• Rac1 links leading edge and uropod events through Rho and myosin activation during chemotaxis.
  Blood 2006 Pestonjamasp KN, Forster C, Sun C, Gardiner EM, Bohl B, Weiner O, Bokoch GM, Glogauer M
• Hem-1 complexes are essential for Rac activation, actin polymerization, and myosin regulation during neutrophil chemotaxis.
  PLoS biology 2006 Weiner OD, Rentel MC, Ott A, Brown GE, Jedrychowski M, Yaffe MB, Gygi SP, Cantley LC, Bourne HR, Kirschner MW
• A chemical compass.
  Nature 2002 Bourne HR, Weiner O
• A PtdInsP(3)- and Rho GTPase-mediated positive feedback loop regulates neutrophil polarity.
  Nature cell biology 2002 Weiner OD, Neilsen PO, Prestwich GD, Kirschner MW, Cantley LC, Bourne HR
• Lipid products of PI(3)Ks maintain persistent cell polarity and directed motility in neutrophils.
  Nature cell biology 2002 Wang F, Herzmark P, Weiner OD, Srinivasan S, Servant G, Bourne HR
• Rac activation: P-Rex1 - a convergence point for PIP(3) and Gbetagamma?
  Current biology : CB 2002 Weiner OD
• Regulation of cell polarity during eukaryotic chemotaxis: the chemotactic compass.
  Current opinion in cell biology 2002 Weiner OD
• PIP3, PIP2, and cell movement--similar messages, different meanings?
  Developmental cell 2001 Insall RH, Weiner OD
• Leukocytes navigate by compass: roles of PI3Kgamma and its lipid products.
  Trends in cell biology 2000 Rickert P, Weiner OD, Wang F, Bourne HR, Servant G
• Polarization of chemoattractant receptor signaling during neutrophil chemotaxis.
  Science (New York, N.Y.) 2000 Servant G, Weiner OD, Herzmark P, Balla T, Sedat JW, Bourne HR
• Enteropathogenic E. coli acts through WASP and Arp2/3 complex to form actin pedestals.
  Nature cell biology 1999 Kalman D, Weiner OD, Goosney DL, Sedat JW, Finlay BB, Abo A, Bishop JM
• Spatial control of actin polymerization during neutrophil chemotaxis.
  Nature cell biology 1999 Weiner OD, Servant G, Welch MD, Mitchison TJ, Sedat JW, Bourne HR
• Dynamics of a chemoattractant receptor in living neutrophils during chemotaxis.
  Molecular biology of the cell 1999 Servant G, Weiner OD, Neptune ER, Sedat JW, Bourne HR
• Medium weight neurofilament mRNA in goldfish Mauthner axoplasm.
  Neuroscience letters 1996 Weiner OD, Zorn AM, Krieg PA, Bittner GD