Orion Weiner, PhD

Cardiovascular Research Institute
+1 415 514-4352

Our lab seeks to define the molecular logic of complex cell behaviors— how cells go from sets of interacting molecules to the emergent properties of living systems. We currently focus on three questions:
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.

Research Summary: 
Cell Polarity During Leukocyte Chemotaxis



Optogenetic control of YAP reveals a dynamic communication code for stem cell fate and proliferation.

Nature communications

Meyer K, Lammers NC, Bugaj LJ, Garcia HG, Weiner OD

Early-life stress triggers long-lasting organismal resilience and longevity via tetraspanin.

bioRxiv : the preprint server for biology

Jiang WI, Belly H, Wang B, Wong A, Kim M, Oh F, DeGeorge J, Huang X, Guang S, Weiner OD, Ma DK

Molecular mechanism of GPCR spatial organization at the plasma membrane.

Nature chemical biology

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

Nagy TL, Strickland JD, Weiner OD

Self-extinguishing relay waves enable homeostatic control of human neutrophil swarming.

bioRxiv : the preprint server for biology

Strickland J, 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.


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

From peptides to proteins: coiled-coil tetramers to single-chain 4-helix bundles.

Chemical science

Naudin EA, Albanese KI, Smith AJ, Mylemans B, Baker EG, Weiner OD, Andrews DM, Tigue N, Savery NJ, Woolfson DN

WASP integrates substrate topology and cell polarity to guide neutrophil migration.

The Journal of cell biology

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

Pipathsouk A, Brunetti RM, Town JP, Graziano BR, Breuer A, Pellett PA, Marchuk K, Tran NT, Krummel MF, Stamou D, Weiner OD

Cell confinement reveals a branched-actin independent circuit for neutrophil polarity.

PLoS biology

Graziano BR, Town JP, Sitarska E, Nagy TL, Fošnaric M, Penic S, Iglic A, Kralj-Iglic V, Gov NS, Diz-Muñoz A, Weiner OD

Live-cell imaging reveals enhancer-dependent Sox2 transcription in the absence of enhancer proximity.


Alexander JM, Guan J, Li B, Maliskova L, Song M, Shen Y, Huang B, Lomvardas S, Weiner OD

Multiple sources of signal amplification within the B-cell Ras/MAPK pathway.

Molecular biology of the cell

Mclaurin JD, Weiner OD

A size-invariant bud-duration timer enables robustness in yeast cell size control.

PloS one

Allard CAH, Decker F, Weiner OD, Toettcher JE, Graziano BR

In pursuit of the mechanics that shape cell surfaces.

Nature physics

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

Saha S, Nagy TL, Weiner OD

Clathrin Assembly Defines the Onset and Geometry of Cortical Patterning.

Developmental cell

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

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)

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

Liu Z, Weiner OD

Membrane Tension Acts Through PLD2 and mTORC2 to Limit Actin Network Assembly During Neutrophil Migration.

PLoS biology

Diz-Muñoz A, Thurley K, Chintamen S, Altschuler SJ, Wu LF, Fletcher DA, Weiner OD

Gß Regulates Coupling between Actin Oscillators for Cell Polarity and Directional Migration.

PLoS biology

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

Buckley CE, Moore RE, Reade A, Goldberg AR, Weiner OD, Clarke JDW

Cell Migration: Recoiling from an Embrace.

Current biology : CB

Genuth MA, Weiner OD

A naturally monomeric infrared fluorescent protein for protein labeling in vivo.

Nature methods

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

Myosin light chain kinase regulates cell polarization independently of membrane tension or Rho kinase.

The Journal of cell biology

Lou SS, Diz-Muñoz A, Weiner OD, Fletcher DA, Theriot JA

Homer3 regulates the establishment of neutrophil polarity.

Molecular biology of the cell

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

Tischer D, Weiner OD

Self-organization of protrusions and polarity during eukaryotic chemotaxis.

Current opinion in cell biology

Graziano BR, Weiner OD

Response to Bell et al.

Molecular biology of the cell

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

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

Hoeller O, Gong D, Weiner OD

How should we be selecting our graduate students?

Molecular biology of the cell

Weiner OD

An optogenetic gene expression system with rapid activation and deactivation kinetics.

Nature chemical biology

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

Dandekar SN, Park JS, Peng GE, Onuffer JJ, Lim WA, Weiner OD

Two distinct functions for PI3-kinases in macropinocytosis.

Journal of cell science

Hoeller O, Bolourani P, Clark J, Stephens LR, Hawkins PT, Weiner OD, Weeks G, Kay RR

Identifying network motifs that buffer front-to-back signaling in polarized neutrophils.

Cell reports

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

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

Woo S, Housley MP, Weiner OD, Stainier DY

Network crosstalk dynamically changes during neutrophil polarization.


Ku CJ, Wang Y, Weiner OD, Altschuler SJ, Wu LF

Membrane tension maintains cell polarity by confining signals to the leading edge during neutrophil migration.


Houk AR, Jilkine A, Mejean CO, Boltyanskiy R, Dufresne ER, Angenent SB, Altschuler SJ, Wu LF, Weiner OD

Light-based feedback for controlling intracellular signaling dynamics.

Nature methods

Toettcher JE, Gong D, Lim WA, Weiner OD

A pharmacological cocktail for arresting actin dynamics in living cells.

Molecular biology of the cell

Peng GE, Wilson SR, Weiner OD

Light control of plasma membrane recruitment using the Phy-PIF system.

Methods in enzymology

Toettcher JE, Gong D, Lim WA, Weiner OD

Sequence-dependent sorting of recycling proteins by actin-stabilized endosomal microdomains.


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.)

Millius A, Weiner OD

Cell stimulation with optically manipulated microsources.

Nature methods

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.


Houk AR, Millius A, Weiner OD

Neutrophils establish rapid and robust WAVE complex polarity in an actin-dependent fashion.

Current biology : CB

Millius A, Dandekar SN, Houk AR, Weiner OD

Chemotaxis in neutrophil-like HL-60 cells.

Methods in molecular biology (Clifton, N.J.)

Millius A, Weiner OD

An actin-based wave generator organizes cell motility.

PLoS biology

Weiner OD, Marganski WA, Wu LF, Altschuler SJ, Kirschner MW

Rac1 links leading edge and uropod events through Rho and myosin activation during chemotaxis.


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

Weiner OD, Rentel MC, Ott A, Brown GE, Jedrychowski M, Yaffe MB, Gygi SP, Cantley LC, Bourne HR, Kirschner MW

A chemical compass.


Bourne HR, Weiner O

A PtdInsP(3)- and Rho GTPase-mediated positive feedback loop regulates neutrophil polarity.

Nature cell biology

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

Wang F, Herzmark P, Weiner OD, Srinivasan S, Servant G, Bourne HR

Leukocytes navigate by compass: roles of PI3Kgamma and its lipid products.

Trends in cell biology

Rickert P, Weiner OD, Wang F, Bourne HR, Servant G

Polarization of chemoattractant receptor signaling during neutrophil chemotaxis.

Science (New York, N.Y.)

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

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

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

Servant G, Weiner OD, Neptune ER, Sedat JW, Bourne HR

Medium weight neurofilament mRNA in goldfish Mauthner axoplasm.

Neuroscience letters

Weiner OD, Zorn AM, Krieg PA, Bittner GD