Works (96)

Updated: May 1st, 2024 05:06

2024 journal article

Quantifying collective motion patterns in mesenchymal cell populations using topological data analysis and agent-based modeling

MATHEMATICAL BIOSCIENCES, 370.

By: K. Nguyen n, C. Jameson*, S. Baldwin n, J. Nardini*, R. Smith n, J. Haugh n, K. Flores n

author keywords: Topological data analysis; Agent-based Modeling; Deep learning; Approximate Bayesian Computation; Cell migration
Sources: Web Of Science, NC State University Libraries
Added: April 22, 2024

2023 article

Dissection of MKK6 and p38 Signaling Using Light-Activated Protein Kinases

Rahman, S. M. T., Zhou, W., Deiters, A., & Haugh, J. M. (2023, November 7). CHEMBIOCHEM, Vol. 11.

By: S. Rahman n, W. Zhou*, A. Deiters* & J. Haugh n

author keywords: apoptosis; autophagy; cell death; growth factors; mitogen-activated protein kinases; optogenetics; signal transduction
TL;DR: Although decaging active p38α does not reduce basal ERK activity in cells, it can block growth factor‐stimulated ERK signaling in serum‐starved cells, which clarifies the roles of MKK6 and p38α in dynamic signaling programs, which act in concert to actuate apoptotic death while suppressing cell survival mechanisms. (via Semantic Scholar)
Sources: Web Of Science, NC State University Libraries
Added: December 4, 2023

2023 journal article

G-actin diffusion is insufficient to achieve F-actin assembly in fast-treadmilling protrusions

BIOPHYSICAL JOURNAL, 122(18), 3816–3829.

By: R. Appalabhotla n, M. Butler*, J. Bear* & J. Haugh n

TL;DR: An experimental system in which cells adopt an approximately constant and symmetrical shape and exhibit fast, steady treadmilling in the thin region protruding from the cell is applied, revealing that diffusion alone cannot account for the transport of G-actin to the leading edge. (via Semantic Scholar)
UN Sustainable Development Goal Categories
14. Life Below Water (OpenAlex)
Sources: Web Of Science, NC State University Libraries
Added: October 30, 2023

2023 article

Isoform-specific optical activation of kinase function reveals p38-ERK signaling crosstalk

Zhou, W., Ryan, A., Janosko, C. P., Shoger, K. E., Haugh, J. M., Gottschalk, R. A., & Deiters, A. (2023, August 25). RSC CHEMICAL BIOLOGY, Vol. 8.

By: W. Zhou, A. Ryan, C. Janosko, K. Shoger, J. Haugh, R. Gottschalk, A. Deiters

UN Sustainable Development Goal Categories
Sources: Web Of Science, NC State University Libraries
Added: October 2, 2023

2023 journal article

Isoform-specific optical activation of kinase function reveals p38-ERK signaling crosstalk

RSC CHEMICAL BIOLOGY, 4(10), 765–773.

By: W. Zhou*, A. Ryan*, C. Janosko*, K. Shoger*, J. Haugh n, R. Gottschalk*, A. Deiters*

TL;DR: Using the photoactivated p38 isoforms, a method for the selective perturbation of the individual protein isoforms of the mitogen-activated protein kinase (MAPK) p38 is described, which identifies a novel point of crosstalk between two major signaling cascades: the p38/MAPK pathway and the extracellular signal-regulated Kinase (ERK)/ MAPK pathway. (via Semantic Scholar)
Sources: Web Of Science, NC State University Libraries
Added: October 16, 2023

2023 journal article

On the inference of ERK signaling dynamics from protein biosensor measurements

MOLECULAR BIOLOGY OF THE CELL, 34(6).

By: S. Rahman n & J. Haugh n

MeSH headings : Biosensing Techniques; Extracellular Signal-Regulated MAP Kinases / metabolism; MAP Kinase Signaling System; Phosphorylation; Signal Transduction
TL;DR: Monitoring ERK signaling using four commonly used translocation- and Förster resonance energy transfer-based biosensors in a common cell stimulation context found that each biosensor responds with unique kinetics; it is clear that there is not a single dynamic signature characterizing the complexity of ERK phosphorylation, translocation, and kinase activity. (via Semantic Scholar)
UN Sustainable Development Goal Categories
Sources: Web Of Science, NC State University Libraries
Added: June 12, 2023

2023 journal article

Semi-autonomous wound invasion via matrix-deposited, haptotactic cues

JOURNAL OF THEORETICAL BIOLOGY, 568.

By: S. Baldwin n & J. Haugh n

author keywords: Cell migration; Wound healing; Gradient sensing; Tissue dynamics; Traveling wave
MeSH headings : Cues; Cell Movement / physiology; Chemotaxis / physiology; Wound Healing / physiology; Fibroblasts; Cytokines
TL;DR: In the present work, it is shown the plausibility of a hypothesis that fibroblasts themselves form and maintain haptotactic gradients in a semi-autonomous fashion, and a positive control scenario where FN is pre-deposited in the wound matrix, and fibro Blasts maintain haaptotaxis by removing FN at an appropriate rate is examined. (via Semantic Scholar)
UN Sustainable Development Goal Categories
Sources: Web Of Science, NC State University Libraries
Added: June 12, 2023

2022 journal article

A kinetic model of phospholipase C-?1 linking structure-based insights to dynamics of enzyme autoinhibition and activation

JOURNAL OF BIOLOGICAL CHEMISTRY, 298(5).

By: J. Nosbisch n, J. Bear* & J. Haugh n

MeSH headings : Animals; Carrier Proteins / metabolism; Isoenzymes / metabolism; Kinetics; Mammals / metabolism; Phospholipase C gamma / genetics; Phospholipase C gamma / metabolism; Phosphorylation; Protein-Tyrosine Kinases / metabolism; Type C Phospholipases / metabolism; src Homology Domains / genetics
TL;DR: A structure-based kinetic model of PLC-γ1 is introduced, considering interactions of its regulatory Src homology 2 (SH2) domains and perturbation of those dynamics upon phosphorylation of Tyr783, a hallmark of activation. (via Semantic Scholar)
Sources: Web Of Science, NC State University Libraries
Added: June 20, 2022

2022 journal article

Modeling cell protrusion predicts how myosin II and actin turnover affect adhesion-based signaling

BIOPHYSICAL JOURNAL, 121(1), 102–118.

By: A. Chandra n, M. Butler*, J. Bear* & J. Haugh n

MeSH headings : Actin Cytoskeleton / metabolism; Actins / metabolism; Cell Surface Extensions; Myosin Type II / metabolism; Signal Transduction
TL;DR: A positive feedback loop is presented, whereby adhesion-based signaling promotes generation of barbed ends at, and protrusion of, the cell's leading edge, which in turn promotes formation and stabilization of nascent adhesions. (via Semantic Scholar)
UN Sustainable Development Goal Categories
Sources: Web Of Science, NC State University Libraries
Added: January 18, 2022

2021 journal article

Microfluidic devices fitted with "flowver" paper pumps generate steady, tunable gradients for extended observation of chemotactic cell migration

BIOMICROFLUIDICS, 15(4).

TL;DR: This work reports on the development of a passive pumping strategy, driven by the high capillary pressure and evaporative capacity of paper, and its application to study fibroblast chemotaxis, and how the orientation of signaling through the phosphoinositide 3-kinase pathway affects the cells' sensing of and response to conducive gradients. (via Semantic Scholar)
Sources: Web Of Science, NC State University Libraries
Added: July 26, 2021

2020 journal article

Mechanistic models of PLC/PKC signaling implicate phosphatidic acid as a key amplifier of chemotactic gradient sensing

PLOS COMPUTATIONAL BIOLOGY, 16(4).

By: J. Nosbisch n, A. Rahman n, K. Mohan n, T. Elston*, J. Bear* & J. Haugh n

MeSH headings : Animals; Chemotaxis / physiology; Diglycerides / metabolism; Fibroblasts / metabolism; Humans; Intracellular Signaling Peptides and Proteins / metabolism; Membrane Proteins / metabolism; Models, Theoretical; Myristoylated Alanine-Rich C Kinase Substrate / metabolism; Phosphatidic Acids / metabolism; Phosphatidic Acids / physiology; Phospholipase D / metabolism; Phosphorylation; Platelet-Derived Growth Factor / metabolism; Protein Kinase C / metabolism; Protein Kinase C / physiology; Signal Transduction / physiology; Type C Phospholipases / metabolism; Type C Phospholipases / physiology
TL;DR: In simulations of wound invasion, efficient collective migration is achieved with thresholds for chemotaxis matching those of polarization in the reaction-diffusion models, and increasing DAG kinase activity can enhance the robustness of DAG/active PKC polarization with respect to chemoattractant concentration while decreasing their whole-cell levels. (via Semantic Scholar)
Sources: Web Of Science, NC State University Libraries
Added: May 26, 2020

2020 journal article

Optical control of MAP kinase kinase 6 (MKK6) reveals that it has divergent roles in pro-apoptotic and anti-proliferative signaling

JOURNAL OF BIOLOGICAL CHEMISTRY, 295(25), 8494–8504.

By: S. Rahman n, W. Zhou*, A. Deiters* & J. Haugh n

author keywords: optogenetics; signal transduction; cell signaling; mitogen-activated protein kinases; apoptosis; cell death; cell stress; mitogen-activated protein kinase (MAPK)
MeSH headings : Animals; Apoptosis / radiation effects; Cell Line; Cell Proliferation / radiation effects; Fibroblasts / cytology; Fibroblasts / metabolism; Humans; MAP Kinase Kinase 6 / genetics; MAP Kinase Kinase 6 / metabolism; Mice; Mitogen-Activated Protein Kinase 1 / metabolism; Mitogen-Activated Protein Kinase 3 / metabolism; Mutagenesis; Protein Isoforms / antagonists & inhibitors; Protein Isoforms / metabolism; Proto-Oncogene Proteins B-raf / genetics; Proto-Oncogene Proteins B-raf / metabolism; Signal Transduction / radiation effects; Ultraviolet Rays; p38 Mitogen-Activated Protein Kinases / antagonists & inhibitors; p38 Mitogen-Activated Protein Kinases / metabolism
TL;DR: MKK6 is position MKK6 as a new pleiotropic signal transducer that promotes both pro-apoptotic and anti-proliferative signaling, and the utility of caged, light-activated kinases for dissecting stress-activated signaling networks is highlighted. (via Semantic Scholar)
UN Sustainable Development Goal Categories
3. Good Health and Well-being (Web of Science; OpenAlex)
Sources: Web Of Science, NC State University Libraries
Added: July 27, 2020

2019 journal article

Design and evaluation of engineered protein biosensors for live-cell imaging of EGFR phosphorylation

SCIENCE SIGNALING, 12(584).

By: K. Tiruthani n, A. Mischler n, S. Ahmed*, J. Mahinthakumar n, J. Haugh n & B. Rao n

MeSH headings : Animals; Biosensing Techniques; Cell Line; Endocytosis; ErbB Receptors / genetics; ErbB Receptors / metabolism; Mice; Microscopy, Fluorescence; Phospholipase C gamma / genetics; Phospholipase C gamma / metabolism; Phosphorylation / genetics; src Homology Domains
TL;DR: The authors used two different mutagenesis and screening approaches to engineer new biosensors, mSH2 and SPY992, that exhibited greater specificity for EGFR Tyr992 and more accurately reported EGFR signaling kinetics, and could be extended to generate phospho-specific biosensor for various targets. (via Semantic Scholar)
UN Sustainable Development Goal Categories
Sources: Web Of Science, NC State University Libraries
Added: June 24, 2019

2019 journal article

Emergent spatiotemporal dynamics of the actomyosin network in the presence of chemical gradients

INTEGRATIVE BIOLOGY, 11(6), 280–292.

By: C. Miller*, P. LaFosse*, S. Asokan*, J. Haugh n, J. Bear* & T. Elston*

MeSH headings : Actin Cytoskeleton / metabolism; Actomyosin / physiology; Animals; Cell Movement; Chemotaxis; Computer Simulation; Fibroblasts / cytology; Humans; Models, Biological; Myosin Type II / metabolism; Pattern Recognition, Automated; Platelet-Derived Growth Factor / metabolism; Signal Transduction
TL;DR: Interestingly, spatial variations in motor stiffness generated time-dependent behavior of the actomyosin network, in which actin asters continued to spontaneously form and dissociate in different regions of the gradient. (via Semantic Scholar)
UN Sustainable Development Goal Categories
Sources: Web Of Science, NC State University Libraries
Added: October 28, 2019

2019 journal article

Simulating Emergent Spatiotemporal Actomyosin Dynamics to Understand Spatial Regulation of Non-Muscle Myosin II

Biophysical Journal, 116(3), 251a.

By: C. Miller*, P. LaFosse*, S. Asokan*, J. Haugh n, J. Bear* & T. Elston*

Sources: Crossref, NC State University Libraries
Added: February 24, 2020

2018 journal article

A Computational Investigation of Asymmetric Emergent Structures in Actomyosin Dynamics During Chemotaxis

Biophysical Journal, 114(3), 381a.

By: C. Miller*, S. Asokan*, J. Haugh n, J. Bear* & T. Elston*

Sources: Crossref, NC State University Libraries
Added: February 24, 2020

2017 journal article

A Reaction-Diffusion Model Explains Amplification of the PLC/PKC Pathway in Fibroblast Chemotaxis

BIOPHYSICAL JOURNAL, 113(1), 185–194.

By: K. Mohan n, J. Nosbisch n, T. Elston*, J. Bear* & J. Haugh n

MeSH headings : Animals; Cell Membrane / metabolism; Chemotaxis / physiology; Diffusion; Feedback, Physiological / physiology; Fibroblasts / enzymology; Intracellular Signaling Peptides and Proteins / metabolism; Membrane Proteins / metabolism; Models, Biological; Myristoylated Alanine-Rich C Kinase Substrate; Phosphorylation; Platelet-Derived Growth Factor / metabolism; Protein Kinase C / metabolism; Signal Transduction / physiology; Type C Phospholipases / metabolism
TL;DR: A reaction-diffusion model of phospholipase C/protein kinase C (PKC) signaling is developed and it is shown that phosphorylation of myristoylated alanine-rich C kinase substrate by membrane-localized PKC constitutes a positive feedback that is sufficient for local pathway amplification. (via Semantic Scholar)
Sources: Web Of Science, NC State University Libraries
Added: August 6, 2018

2017 journal article

Kinetic Modeling and Analysis of the Akt/Mechanistic Target of Rapamycin Complex 1 (mTORC1) Signaling Axis Reveals Cooperative, Feedforward Regulation

JOURNAL OF BIOLOGICAL CHEMISTRY, 292(7), 2866–2872.

By: A. Rahman n & J. Haugh n

MeSH headings : Animals; Kinetics; Mechanistic Target of Rapamycin Complex 1; Mice; Models, Biological; Multiprotein Complexes / metabolism; NIH 3T3 Cells; Proto-Oncogene Proteins c-akt / metabolism; Signal Transduction; TOR Serine-Threonine Kinases / metabolism
TL;DR: A model based on a putative feedforward loop orchestrated by Akt consistently predicted how the pathway was altered by depletion of key regulatory proteins, and elucidates two dynamical motifs: neutralization of a negative regulator, which characterizes how Akt indirectly activates m TORC1, and seesaw enzyme regulation, which describes how activated and inhibited states of mTORC1 are controlled in concert to produce a nonlinear, ultrasensitive response. (via Semantic Scholar)
Sources: Web Of Science, ORCID, NC State University Libraries
Added: August 6, 2018

2016 journal article

Are Filopodia Privileged Signaling Structures in Migrating Cells?

BIOPHYSICAL JOURNAL, 111(9), 1827–1830.

By: H. Johnson n & J. Haugh n

MeSH headings : Animals; Cell Movement; Mice; NIH 3T3 Cells; Optical Imaging; Pseudopodia / metabolism; Signal Transduction
TL;DR: This work analyzed total internal reflection fluorescence images of migrating fibroblasts coexpressing either a plasma membrane marker or tagged AktPH domain, a translocation biosensor for signaling through the phosphoinositide 3-kinase pathway, along with a cytosolic volume marker to support the filopodial signaling hypothesis. (via Semantic Scholar)
Sources: Web Of Science, ORCID, NC State University Libraries
Added: August 6, 2018

2016 journal article

Lamellipodia are crucial for haptotactic sensing and response

JOURNAL OF CELL SCIENCE, 129(12), 2329–2342.

By: S. King*, S. Asokan*, E. Haynes*, S. Zimmerman*, J. Rotty*, J. Alb*, A. Tagliatela*, D. Blake* ...

author keywords: Haptotaxis; Arp2/3; Lamellipodia; Directed migration
MeSH headings : Actin-Related Protein 2-3 Complex / metabolism; Actins / metabolism; Animals; Chemotaxis / drug effects; Fibroblasts / cytology; Fibroblasts / drug effects; Fibroblasts / metabolism; Fibronectins / pharmacology; Focal Adhesion Protein-Tyrosine Kinases / metabolism; Focal Adhesions / metabolism; Guanine Nucleotide Exchange Factors / metabolism; Integrin beta1 / metabolism; Mice; Models, Biological; Pseudopodia / metabolism; Signal Transduction / drug effects; T-Lymphoma Invasion and Metastasis-inducing Protein 1; Wiskott-Aldrich Syndrome Protein / metabolism; Wiskott-Aldrich Syndrome Protein Family / metabolism; rac GTP-Binding Proteins / metabolism; src-Family Kinases / metabolism
TL;DR: Haptotaxis (directed migration) on a substrate-bound gradient is perhaps the least-well understood form of directed migration and it is shown that differential lamellipodial dynamics are crucial for this process. (via Semantic Scholar)
Sources: Web Of Science, ORCID, NC State University Libraries
Added: August 6, 2018

2016 journal article

Quantitative analysis of B-lymphocyte migration directed by CXCL13

INTEGRATIVE BIOLOGY, 8(8), 894–903.

By: X. Liu n, S. Asokan*, J. Bear* & J. Haugh n

MeSH headings : Adsorption; Animals; B-Lymphocytes / cytology; Cell Movement; Chemokine CXCL13 / metabolism; Computational Biology; Computer Simulation; Intercellular Adhesion Molecule-1 / metabolism; Mice; Mice, Inbred C57BL; Microfluidics; Microscopy, Fluorescence; Phenotype
TL;DR: TIRF microscopy was used to characterize the changes in shape (morphodynamics) of primary, murine B cells as they migrated on surfaces with adsorbed chemokine, CXCL13, and the adhesive ligand, ICAM-1, and showed that B-cell migration is more persistent when the direction of migration is better aligned with the gradient. (via Semantic Scholar)
Sources: Web Of Science, ORCID, NC State University Libraries
Added: August 6, 2018

2016 article

Systems Cell Biology: An Overview

Encyclopedia of Cell Biology, pp. 1–3.

By: D. Lauffenburger*, J. Haugh n, H. Byrne* & R. Linding*

Source: ORCID
Added: July 13, 2021

2015 journal article

Development of a tandem affinity phosphoproteomic method with motif selectivity and its application in analysis of signal transduction networks

JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL AND LIFE SCIENCES, 988, 166–174.

By: L. Herring n, K. Grant*, K. Blackburn n, J. Haugh n & M. Goshe n

author keywords: Phosphopeptide enrichment; Liquid chromatography; Mass spectrometry; Motif analysis; Pathway analysis
MeSH headings : Amino Acid Sequence; Chromatography, Liquid / methods; Molecular Sequence Data; Phosphopeptides / analysis; Phosphopeptides / chemistry; Proteomics / methods; Signal Transduction / physiology; Tandem Mass Spectrometry / methods
TL;DR: A multi-dimensional method incorporating electrostatic repulsion-hydrophilic interaction chromatography (ERLIC) with tandem IMAC/TiO2 enrichment for subsequent phosphopeptide identification by LC/MS/MS and biological functions that were over-represented at each PDGF stimulation time point illustrate the feasibility of this approach in quantitative phosphoproteomic studies. (via Semantic Scholar)
Sources: Web Of Science, ORCID, NC State University Libraries
Added: August 6, 2018

2015 journal article

F-actin bundles direct the initiation and orientation of lamellipodia through adhesion-based signaling

JOURNAL OF CELL BIOLOGY, 208(4), 443–455.

By: H. Johnson n, S. King*, S. Asokan*, J. Rotty*, J. Bear* & J. Haugh n

MeSH headings : 3T3 Cells; Actin Cytoskeleton; Actin-Related Protein 2-3 Complex / genetics; Actin-Related Protein 2-3 Complex / metabolism; Actins / physiology; Animals; Cell Adhesion / physiology; Cell Line; Cell Shape; Chemotaxis / genetics; Chemotaxis / physiology; Fibroblasts / cytology; Fibronectins / metabolism; Focal Adhesion Protein-Tyrosine Kinases / metabolism; Mice; Microfilament Proteins / biosynthesis; Microfilament Proteins / genetics; Microscopy, Fluorescence; Molecular Sequence Data; Phosphatidylinositol 3-Kinases / metabolism; Platelet-Derived Growth Factor / metabolism; Pseudopodia / physiology; RNA Interference; RNA, Small Interfering; Receptors, Odorant / biosynthesis; Receptors, Odorant / genetics
TL;DR: During cell migration, F-actin bundles/filopodia serve as templates for formation and orientation of lamellipodia and prime their stabilization by adhesion-based PI3K signaling. (via Semantic Scholar)
Sources: Web Of Science, ORCID, NC State University Libraries
Added: August 6, 2018

2015 journal article

GMF beta controls branched actin content and lamellipodial retraction in fibroblasts

JOURNAL OF CELL BIOLOGY, 209(6), 803–812.

By: E. Haynes*, S. Asokan*, S. King*, H. Johnson n, J. Haugh n & J. Bear*

MeSH headings : Actin-Related Protein 2-3 Complex / antagonists & inhibitors; Actin-Related Protein 2-3 Complex / metabolism; Actins / biosynthesis; Animals; Cell Line; Cell Movement / physiology; Enzyme Activation; Fibroblasts / physiology; Fibronectins / pharmacology; Glia Maturation Factor / physiology; Indoles / pharmacology; Mice; Protein Isoforms / biosynthesis; Pseudopodia / physiology
Sources: Web Of Science, ORCID, NC State University Libraries
Added: August 6, 2018

2015 journal article

Linking morphodynamics and directional persistence of T lymphocyte migration

JOURNAL OF THE ROYAL SOCIETY INTERFACE, 12(106).

By: X. Liu n, E. Welf n & J. Haugh n

author keywords: cell migration; chemokine; TIRF microscopy; image analysis
MeSH headings : Actins / physiology; Animals; Cell Movement / physiology; Cell Polarity / physiology; Cell Size; Cells, Cultured; Computer Simulation; Humans; Membrane Fluidity / physiology; Mice; Models, Biological; Models, Statistical; Molecular Motor Proteins / physiology; Stochastic Processes; T-Lymphocytes / cytology; T-Lymphocytes / physiology
TL;DR: This study uses total internal reflection fluorescence microscopy to monitor T lymphocytes' areas of contact with a surface presenting adhesive ICAM-1 and the chemokine, and suggests that switching of the dominant protrusion between the two sides of the migration axis is associated with persistent migration, whereas the opposite is true of cell turning. (via Semantic Scholar)
Sources: Web Of Science, NC State University Libraries
Added: August 6, 2018

2015 journal article

Profilin-1 Serves as a Gatekeeper for Actin Assembly by Arp2/3-Dependent and -Independent Pathways

DEVELOPMENTAL CELL, 32(1), 54–67.

MeSH headings : Actin Cytoskeleton / metabolism; Actin-Related Protein 2-3 Complex / metabolism; Actins / metabolism; Animals; Female; Fetal Proteins; Fibroblasts / cytology; Formins; Image Processing, Computer-Assisted; Male; Mice; Mice, Inbred C57BL; Microfilament Proteins; Microscopy, Fluorescence; Nuclear Proteins; Profilins / metabolism; Signal Transduction; Stress Fibers
TL;DR: Antagonism of the Arp2/3 complex by profilin-1 in cells appears to maintain actin homeostasis by balancing Arp1/2 complex-dependent and -independent actin assembly pathways. (via Semantic Scholar)
Sources: Web Of Science, ORCID, NC State University Libraries
Added: August 6, 2018

2014 journal article

Bi-ligand surfaces with oriented and patterned protein for real-time tracking of cell migration

COLLOIDS AND SURFACES B-BIOINTERFACES, 123, 225–235.

By: V. Vernekar*, C. Wallace*, M. Wu*, J. Chao*, . Shannon K. O'Connor, A. Raleigh*, X. Liu n, J. Haugh n, W. Reichert*

author keywords: Chemotaxis; Chemokine; Cell adhesion molecule; Surface immobilization; Surface gradients; B lymphocyte
MeSH headings : Animals; B-Lymphocytes / cytology; Cell Movement / physiology; Cells, Cultured; Chemokine CXCL12 / chemistry; Intercellular Adhesion Molecule-1 / chemistry; Mice; Mice, Transgenic; Ultraviolet Rays
TL;DR: This test platform can be especially valuable for investigators interested in studying the influence of surface-immobilized factors on cell behavior and may also be used as a cell migration enabling platform for testing the effects of various diffusible agents. (via Semantic Scholar)
Sources: Web Of Science, ORCID, NC State University Libraries
Added: August 6, 2018

2014 journal article

Data-driven modeling reconciles kinetics of ERK phosphorylation, localization, and activity states

MOLECULAR SYSTEMS BIOLOGY, 10(1).

By: S. Ahmed n, K. Grant n, L. Edwards n, A. Rahman n, M. Cirit n, M. Goshe n, J. Haugh n

author keywords: growth factor receptors; mitogen-activated protein kinases; negative feedback; nucleocytoplasmic shuttling; mathematical model
MeSH headings : Active Transport, Cell Nucleus; Animals; Extracellular Signal-Regulated MAP Kinases / chemistry; Extracellular Signal-Regulated MAP Kinases / metabolism; Feedback, Physiological; Kinetics; Mice; Models, Theoretical; NIH 3T3 Cells; Phosphorylation; Protein Transport / genetics; Receptors, Growth Factor / genetics; Signal Transduction / genetics
Sources: Web Of Science, ORCID, NC State University Libraries
Added: August 6, 2018

2014 journal article

Deactivation of a Negative Regulator: A Distinct Signal Transduction Mechanism, Pronounced in Akt Signaling

BIOPHYSICAL JOURNAL, 107(10), L29–L32.

By: A. Rahman n & J. Haugh n

MeSH headings : Kinetics; Models, Biological; Phosphorylation; Proto-Oncogene Proteins c-akt / metabolism; Signal Transduction
TL;DR: It is shown that the indirect mechanism, pervasive in Akt signaling, has properties that are distinct from direct activation, and can be integrated in network motifs to produce desired responses, as in the case of feedforward loops. (via Semantic Scholar)
Sources: Web Of Science, ORCID, NC State University Libraries
Added: August 6, 2018

2014 journal article

Directed migration of mesenchymal cells: where signaling and the cytoskeleton meet

CURRENT OPINION IN CELL BIOLOGY, 30, 74–82.

By: J. Bear* & J. Haugh n

MeSH headings : Actin Cytoskeleton / metabolism; Cell Movement / physiology; Cytoskeleton / metabolism; Fibroblasts / cytology; Fibroblasts / metabolism; Neutrophils / cytology; Neutrophils / metabolism; Signal Transduction
TL;DR: The emerging hypothesis is that the molecular underpinnings of mesenchymal taxis involve distinct signaling pathways and diverse requirements for regulation. (via Semantic Scholar)
Sources: Web Of Science, ORCID, NC State University Libraries
Added: August 6, 2018

2014 journal article

Mesenchymal Chemotaxis Requires Selective Inactivation of Myosin II at the Leading Edge via a Noncanonical PLC gamma/PKC alpha Pathway

DEVELOPMENTAL CELL, 31(6), 747–760.

By: S. Asokan*, H. Johnson n, A. Rahman n, S. King*, J. Rotty*, I. Lebedeva*, J. Haugh n, J. Bear*

MeSH headings : Animals; Cell Line; Cell Movement; Chemotaxis / physiology; Diglycerides / chemistry; Green Fluorescent Proteins / metabolism; Humans; Ligands; Mesoderm / physiology; Mice; Mice, Transgenic; Myosin Type II / metabolism; Phorbol Esters; Phospholipase C gamma / metabolism; Phosphorylation; Platelet-Derived Growth Factor / metabolism; Protein Kinase C-alpha / metabolism; Signal Transduction
TL;DR: It is demonstrated that local inactivation of Myosin IIA, through a noncanonical Ser1/2 phosphorylation of the regulatory light chain, is essential for mesenchymal chemotaxis and subsequent inhibition of MyOSin II activity at the leading edge are required. (via Semantic Scholar)
Sources: Web Of Science, ORCID, NC State University Libraries
Added: August 6, 2018

2013 journal article

Bidirectional coupling between integrin-mediated signaling and actomyosin mechanics explains matrix-dependent intermittency of leading-edge motility

MOLECULAR BIOLOGY OF THE CELL, 24(24), 3945–3955.

By: E. Welf n, H. Johnson n & J. Haugh n

MeSH headings : Actin Cytoskeleton; Actins / metabolism; Actomyosin / physiology; Animals; Cell Adhesion / physiology; Cell Adhesion Molecules / genetics; Cell Movement / physiology; Computer Simulation; Extracellular Matrix / metabolism; Focal Adhesions / physiology; Integrins / genetics; Integrins / metabolism; Integrins / physiology; Mechanotransduction, Cellular; Myosin Type II / metabolism; Pseudopodia / metabolism; Signal Transduction / genetics; rhoA GTP-Binding Protein / metabolism
TL;DR: A physicochemical model is used to describe the coupling of adhesion, cytoskeletal, and signaling dynamics during cell migration, and analysis of stochastic simulations predicts relationships between measurable quantities that reflect partitioning of stress between F-actin–bound adhesions. (via Semantic Scholar)
Sources: Web Of Science, ORCID, NC State University Libraries
Added: August 6, 2018

2013 journal article

Fibroblast Migration Is Regulated by Myristoylated Alanine-Rich C-Kinase Substrate (MARCKS) Protein

PLOS ONE, 8(6).

By: L. Ott n, E. Sung n, A. Melvin n, M. Sheats n, J. Haugh n, K. Adler n, S. Jones n

Ed(s): P. Aspenstrom

MeSH headings : 3T3 Cells; Animals; Becaplermin; Chemotaxis / drug effects; Chemotaxis / physiology; Collagen / metabolism; Fibroblasts / cytology; Fibronectins / metabolism; Intracellular Signaling Peptides and Proteins / metabolism; Intracellular Signaling Peptides and Proteins / physiology; Membrane Proteins / metabolism; Membrane Proteins / physiology; Mice; Myristoylated Alanine-Rich C Kinase Substrate; Phosphorylation; Proto-Oncogene Proteins c-akt / metabolism; Proto-Oncogene Proteins c-sis / pharmacology
TL;DR: Genetic structure-function analysis revealed that MANS peptide-mediated attenuation of NIH-3T3 cell migration does not require the presence of the myristic acid moiety on the amino-terminus, and suggests that MARCKS-mediated regulation of fibroblast migration involves the MARC KS amino- terminus. (via Semantic Scholar)
Sources: Web Of Science, ORCID, NC State University Libraries
Added: August 6, 2018

2013 article

Quantitative Analysis of Phosphoinositide 3-Kinase (PI3K) Signaling Using Live-Cell Total Internal Reflection Fluorescence (TIRF) Microscopy

Current Protocols in Cell Biology.

By: H. Johnson n & J. Haugh n

MeSH headings : Animals; Green Fluorescent Proteins / genetics; Green Fluorescent Proteins / metabolism; Image Processing, Computer-Assisted; Mice; Microscopy, Fluorescence / methods; NIH 3T3 Cells; Phosphatidylinositol 3-Kinases / metabolism; Phosphoprotein Phosphatases / genetics; Phosphoprotein Phosphatases / metabolism; Protein Binding; Protein Transport; Receptor Cross-Talk; Recombinant Fusion Proteins / genetics; Signal Transduction
TL;DR: This unit focuses on the use of total internal reflection fluorescence (TIRF) microscopy and image analysis methods to study the dynamics of signal transduction mediated by class I phosphoinositide 3‐kinases (PI3Ks) in mammalian cells. (via Semantic Scholar)
Source: ORCID
Added: July 13, 2021

2012 article

Cell regulation: A time to signal, a time to respond (Comment on DOI 10.1002/bies.201100172)

Haugh, J. M. (2012, July). BIOESSAYS, Vol. 34, pp. 528–529.

By: J. Haugh n

MeSH headings : Animals; Cell Communication; Extracellular Signal-Regulated MAP Kinases / metabolism; Gene Regulatory Networks; Humans; Models, Theoretical; Signal Transduction
TL;DR: The notion is that the complexity of the problem can be reduced by splitting it into two parts: one, the convergence of receptor-mediated pathways resulting in activation of a handful of master regulators, and two, the influences of those regulators on cell behaviour. (via Semantic Scholar)
Sources: Web Of Science, ORCID, NC State University Libraries
Added: August 6, 2018

2012 journal article

Data-driven modelling of receptor tyrosine kinase signalling networks quantifies receptor-specific potencies of PI3K-and Ras-dependent ERK activation

BIOCHEMICAL JOURNAL, 441(1), 77–85.

By: M. Cirit n & J. Haugh n

author keywords: computational biology; cross-talk; growth factor; kinetic analysis; mitogen-activated protein kinase (MAPK); receptor tyrosine kinase
MeSH headings : Animals; Becaplermin; Computer Simulation; Extracellular Signal-Regulated MAP Kinases / genetics; Extracellular Signal-Regulated MAP Kinases / metabolism; Fibroblast Growth Factor 2 / genetics; Fibroblast Growth Factor 2 / metabolism; Fibroblasts / metabolism; Gene Expression Regulation, Enzymologic; Humans; Kinetics; Mice; Models, Biological; NIH 3T3 Cells; Phosphatidylinositol 3-Kinases / genetics; Phosphatidylinositol 3-Kinases / metabolism; Proto-Oncogene Proteins c-sis / genetics; Proto-Oncogene Proteins c-sis / metabolism; Receptor Protein-Tyrosine Kinases / genetics; Receptor Protein-Tyrosine Kinases / metabolism; Receptors, Fibroblast Growth Factor / genetics; Receptors, Fibroblast Growth Factor / metabolism; Signal Transduction
TL;DR: It is shown that, whereas the FGF stimulation of PI3K signalling is relatively weak, this deficiency is compensated for by a more potent Ras-dependent activation of ERK, and the ERK pathway is activated to a greater extent in cells co-stimulated with FGF and PDGF, relative to the saturated levels achieved with either ligand alone. (via Semantic Scholar)
Sources: Web Of Science, ORCID, NC State University Libraries
Added: August 6, 2018

2012 journal article

Erratum to: Stochastic Dynamics of Membrane Protrusion Mediated by the DOCK180/Rac Pathway in Migrating Cells

Cellular and Molecular Bioengineering, 5(4), 514–516.

By: E. Welf n & J. Haugh n

Sources: Crossref, NC State University Libraries
Added: February 24, 2020

2012 journal article

Live-Cell Fluorescence Microscopy with Molecular Biosensors: What Are We Really Measuring?

BIOPHYSICAL JOURNAL, 102(9), 2003–2011.

By: J. Haugh n

MeSH headings : Animals; Humans; Microscopy, Fluorescence / methods; Molecular Imaging / methods; Molecular Probe Techniques; Molecular Probes / metabolism; Protein Interaction Mapping / methods
TL;DR: To address the pitfalls of the biosensor approach in quantitative terms, simple reaction-diffusion models were analyzed and a sobering insight emerges: the observer or saturation effect is always significant; the question is whether or not it can be tolerated or accounted for. (via Semantic Scholar)
UN Sustainable Development Goal Categories
7. Affordable and Clean Energy (OpenAlex)
Sources: Web Of Science, ORCID, NC State University Libraries
Added: August 6, 2018

2012 journal article

Migrating fibroblasts reorient directionality by a metastable, PI3K-dependent mechanism

JOURNAL OF CELL BIOLOGY, 197(1), 105–114.

By: E. Welf n, S. Ahmed n, H. Johnson n, A. Melvin n & J. Haugh n

MeSH headings : Animals; Cell Movement; Cells, Cultured; Fibroblasts / cytology; Fibroblasts / enzymology; Fibroblasts / metabolism; Mice; NIH 3T3 Cells; Phosphatidylinositol 3-Kinases / metabolism; Phosphoinositide-3 Kinase Inhibitors; Signal Transduction / drug effects
TL;DR: Migrating fibroblasts reorient directionality by PI3K-dependent branching and pivoting of protrusions, a mechanism that allows fibro Blasts to align with an external chemotactic gradient. (via Semantic Scholar)
Sources: Web Of Science, ORCID, NC State University Libraries
Added: August 6, 2018

2012 article

Stochastic Models of Cell Protrusion Arising From Spatiotemporal Signaling and Adhesion Dynamics

Computational Methods in Cell Biology, pp. 223–241.

By: E. Welf n & J. Haugh n

MeSH headings : Algorithms; Animals; CHO Cells; Cell Adhesion; Cell Movement; Cell Shape; Computer Simulation; Cricetinae; Kinetics; Models, Biological; Signal Transduction / physiology; Stochastic Processes
TL;DR: This chapter presents a modeling approach for integrating the apparent stochasticity and spatial dependence of signal transduction pathways that promote protrusion in tandem with adhesion dynamics, as well as its abstraction, parameterization, and validation against experimental data. (via Semantic Scholar)
Source: ORCID
Added: July 13, 2021

2012 article

Stochastic dynamics of membrane protrusion mediated by the DOCK180/Rac pathway in migrating cells (vol 3, pg 30, 2010)

Cellular and Molecular Bioengineering, Vol. 5, pp. 514–516.

By: E. Welf & J. Haugh

Source: NC State University Libraries
Added: August 6, 2018

2012 conference paper

Stochastic models of cell protrusion arising from spatiotemporal signaling and adhesion dynamics

Methods in cell biology, vol 110: computational methods in cell biology, 110, 223–241.

By: E. Welf & J. Haugh

Source: NC State University Libraries
Added: August 6, 2018

2012 journal article

Systemic Perturbation of the ERK Signaling Pathway by the Proteasome Inhibitor, MG132

PLOS ONE, 7(11).

By: M. Cirit n, K. Grant n & J. Haugh n

Ed(s): L. Buday

MeSH headings : Animals; Computer Simulation; Dual-Specificity Phosphatases / metabolism; Embryo, Mammalian / cytology; Enzyme Activation / drug effects; Fibroblast Growth Factors / pharmacology; Fibroblasts / cytology; Fibroblasts / drug effects; Fibroblasts / enzymology; Humans; Leupeptins / pharmacology; MAP Kinase Signaling System / drug effects; Mesoderm / cytology; Mice; Mitogen-Activated Protein Kinase Kinases / metabolism; NIH 3T3 Cells; Phosphorylation / drug effects; Platelet-Derived Growth Factor / pharmacology; Proteasome Inhibitors / pharmacology; Up-Regulation / drug effects
TL;DR: It is shown that the effects of MG132 treatment on ERK signaling are more widespread, leading to a reduction in activation of the upstream kinase MEK, suggesting that MG132 systemically perturbs the intracellular phosphoproteome, impactingERK signaling by reducing phosphorylation status at multiple levels of the kinase cascade. (via Semantic Scholar)
Sources: Web Of Science, ORCID, NC State University Libraries
Added: August 6, 2018

2011 journal article

Allosteric Modulation of Ras-GTP Is Linked to Signal Transduction through RAF Kinase

JOURNAL OF BIOLOGICAL CHEMISTRY, 286(5), 3323–3331.

By: G. Buhrman*, V. Kumar, M. Cirit n, J. Haugh n & C. Mattos*

MeSH headings : Allosteric Regulation; Allosteric Site; Animals; Guanosine Triphosphate / metabolism; Kinetics; Mice; Mutation, Missense; NIH 3T3 Cells; Protein Conformation; Protein Stability; Signal Transduction; raf Kinases / metabolism; ras Proteins / genetics; ras Proteins / metabolism
TL;DR: The allosteric switch is linked to the control of signaling in the Ras/Raf/MEK/ERK pathway, supporting a GTPase-activating protein-independent model for duration of the Ras-Raf complex. (via Semantic Scholar)
Sources: Web Of Science, ORCID, NC State University Libraries
Added: August 6, 2018

2011 journal article

Cells see the light to bring signaling under control

Nature Methods, 8(10), 808–809.

By: J. Haugh n

MeSH headings : Animals; Feedback, Physiological / radiation effects; Humans; Light; Signal Transduction / radiation effects
TL;DR: The combination of optogenetics with feedback control counteracts variability in cellular signaling responses to promote a deeper understanding of the biochemical mechanisms involved. (via Semantic Scholar)
UN Sustainable Development Goal Categories
2. Zero Hunger (Web of Science)
13. Climate Action (Web of Science)
Sources: NC State University Libraries, ORCID, NC State University Libraries
Added: August 6, 2018

2011 journal article

Guidelines for visualizing and annotating rule-based models

MOLECULAR BIOSYSTEMS, 7(10), 2779–2795.

By: L. Chylek*, B. Hu*, M. Blinov*, T. Emonet*, J. Faeder*, B. Goldstein*, R. Gutenkunst*, J. Haugh n ...

MeSH headings : Allosteric Regulation; Models, Theoretical; Signal Transduction
TL;DR: The concepts of an extended contact map and a model guide for illustrating and annotating rule-based models, which can document knowledge of a cell signaling system in a form that is visual as well as executable, are developed. (via Semantic Scholar)
Sources: Web Of Science, ORCID, NC State University Libraries
Added: August 6, 2018

2011 journal article

In Chemotaxing Fibroblasts, Both High-Fidelity and Weakly Biased Cell Movements Track the Localization of PI3K Signaling

BIOPHYSICAL JOURNAL, 100(8), 1893–1901.

By: A. Melvin n, E. Welf n, Y. Wang*, D. Irvine* & J. Haugh n

MeSH headings : Alginates / chemistry; Animals; Cell Surface Extensions / drug effects; Cell Surface Extensions / metabolism; Chemotaxis / drug effects; Dose-Response Relationship, Drug; Fibroblasts / cytology; Fibroblasts / drug effects; Fibroblasts / enzymology; Glucuronic Acid / chemistry; Hexuronic Acids / chemistry; Mice; Microspheres; NIH 3T3 Cells; Phosphatidylinositol 3-Kinases / metabolism; Platelet-Derived Growth Factor / chemistry; Platelet-Derived Growth Factor / pharmacology; Receptors, Platelet-Derived Growth Factor / metabolism; Signal Transduction / drug effects; Stochastic Processes
TL;DR: It is shown that persistent and properly aligned (i.e., high-fidelity) fibroblast migration does indeed correlate with polarized PI3K signaling; accordingly, this behavior is seen only under conditions of high gradient steepness and a certain range of PDGF concentrations. (via Semantic Scholar)
Sources: Web Of Science, ORCID, NC State University Libraries
Added: August 6, 2018

2011 article

PI3K-dependent cross-talk interactions converge with Ras as quantifiable inputs integrated by Erk (vol 5, pg 246, 2009)

Wang, C.-C., Cirit, M., & Haugh, J. M. (2011, August). MOLECULAR SYSTEMS BIOLOGY, Vol. 7.

By: C. Wang n, M. Cirit n & J. Haugh n

TL;DR: The effects of expressing wild-type and genuine G12V H-Ras in the authors' cells, using the samemethods as in the published article, are presented. (via Semantic Scholar)
UN Sustainable Development Goal Categories
Sources: ORCID, NC State University Libraries, Web Of Science
Added: August 6, 2018

2011 journal article

Poly(vinylmethylsiloxane) Elastomer Networks as Functional Materials for Cell Adhesion and Migration Studies

BIOMACROMOLECULES, 12(4), 1265–1271.

By: S. Ahmed n, H. Yang n, A. Ozcam n, K. Efimenko n, M. Weiger n, J. Genzer n, J. Haugh n

MeSH headings : Amino Acid Sequence; Animals; Cell Adhesion; Cell Movement; Mice; Microscopy, Fluorescence; Molecular Sequence Data; NIH 3T3 Cells; Oligopeptides / chemistry; Polyvinyls / chemistry; Siloxanes / chemistry
TL;DR: These experiments show that a peptide containing the synergy sequence of fibronectin (PHSRN) in addition to RGD promotes more productive cell migration without markedly enhancing cell adhesion strength. (via Semantic Scholar)
UN Sustainable Development Goal Categories
Sources: Web Of Science, ORCID, NC State University Libraries
Added: August 6, 2018

2011 journal article

Quantitative models of signal transduction networks

Communicative & Integrative Biology, 4(3), 353–356.

By: M. Cirit n & J. Haugh n

TL;DR: It is argued that the level of detail in models of signaling networks ought to be limited by the availability of quantitative data, rather than by the much greater availability of qualitative information about signaling interactions. (via Semantic Scholar)
Source: ORCID
Added: July 13, 2021

2011 journal article

Signaling pathways that control cell migration: models and analysis

WILEY INTERDISCIPLINARY REVIEWS-SYSTEMS BIOLOGY AND MEDICINE, 3(2), 231–240.

By: E. Welf n & J. Haugh n

MeSH headings : Cell Movement / physiology; Humans; Models, Biological; Signal Transduction / physiology; Systems Biology
TL;DR: Some of the more recent applications of quantitative modeling and analysis in the field of cell migration are highlighted and it is clear that the challenge ahead will be to characterize the couplings between them in an integrated framework. (via Semantic Scholar)
Sources: Web Of Science, ORCID, NC State University Libraries
Added: August 6, 2018

2010 journal article

Directional Persistence of Cell Migration Coincides with Stability of Asymmetric Intracellular Signaling

BIOPHYSICAL JOURNAL, 98(1), 67–75.

By: M. Weiger n, S. Ahmed n, E. Welf n & J. Haugh n

MeSH headings : Animals; Cell Movement / physiology; Computer Simulation; Mice; Models, Biological; NIH 3T3 Cells; Phosphatidylinositol 3-Kinases; Signal Transduction / physiology
TL;DR: Analysis of phosphoinositide 3-kinase signaling in randomly migrating fibroblasts shows that hot spots of intense signaling coincide with localized cell protrusion and endure with characteristic lifetimes that correspond to those of cell migration persistence, and shows that distant hot spots are dynamically and stochastically coupled. (via Semantic Scholar)
Sources: Web Of Science, ORCID, NC State University Libraries
Added: August 6, 2018

2010 journal article

Stochastic Dynamics of Membrane Protrusion Mediated by the DOCK180/Rac Pathway in Migrating Cells

CELLULAR AND MOLECULAR BIOENGINEERING, 3(1), 30–39.

By: E. Welf n & J. Haugh n

author keywords: Integrins; Focal adhesions; Signal transduction; Paxillin; Src-family kinases; Myosin
TL;DR: It is shown that this “buffering of inhibition” mechanism, coupled with the core protrusion cycle, is capable of tuning the frequencies of protrusion and adhesion maturation events. (via Semantic Scholar)
Sources: Web Of Science, ORCID, NC State University Libraries
Added: August 6, 2018

2010 journal article

Stochastic Model of Integrin-Mediated Signaling and Adhesion Dynamics at the Leading Edges of Migrating Cells

PLOS COMPUTATIONAL BIOLOGY, 6(2).

By: M. Cirit n, M. Krajcovic n, C. Choi*, E. Welf n, A. Horwitz* & J. Haugh n

Ed(s): A. Asthagiri

MeSH headings : Animals; CHO Cells; Cell Adhesion / physiology; Cell Movement / physiology; Cell Surface Extensions / metabolism; Computational Biology / methods; Computer Simulation; Cricetinae; Cricetulus; Extracellular Matrix / metabolism; Green Fluorescent Proteins / genetics; Green Fluorescent Proteins / metabolism; Integrins / metabolism; Models, Biological; Myosins / metabolism; Paxillin / genetics; Paxillin / metabolism; Signal Transduction / physiology; Stochastic Processes; rac GTP-Binding Proteins / metabolism
TL;DR: This work has formulated a quantitative model of leading edge dynamics combining mechanistic and phenomenological elements and studied its features through classical bifurcation analysis and stochastic simulation, showing that the qualitative behavior of the model is most sensitive to parameters characterizing the influence of stable adhesion and myosin. (via Semantic Scholar)
UN Sustainable Development Goal Categories
10. Reduced Inequalities (OpenAlex)
Sources: Web Of Science, ORCID, NC State University Libraries
Added: August 6, 2018

2010 journal article

Systematic Quantification of Negative Feedback Mechanisms in the Extracellular Signal-regulated Kinase (ERK) Signaling Network

JOURNAL OF BIOLOGICAL CHEMISTRY, 285(47), 36736–36744.

By: M. Cirit n, C. Wang n & J. Haugh n

MeSH headings : Animals; Extracellular Signal-Regulated MAP Kinases / metabolism; Feedback, Physiological; Humans; Immunoblotting; Kinetics; Mice; Mitogen-Activated Protein Kinases / metabolism; NIH 3T3 Cells; Phosphorylation; Signal Transduction; ras Proteins / metabolism
TL;DR: This work takes a systematic approach to parse the magnitudes of multiple regulatory mechanisms that attenuate ERK activation through canonical (Ras- dependent) and non-canonical (PI3K-dependent) pathways and demonstrates that kinetic models of signaling networks, trained on a sufficient diversity of quantitative data, can be reasonably comprehensive, accurate, and predictive in the dynamical sense. (via Semantic Scholar)
Sources: Web Of Science, ORCID, NC State University Libraries
Added: August 6, 2018

2009 journal article

A Bipolar Clamp Mechanism for Activation of Jak-Family Protein Tyrosine Kinases

PLOS COMPUTATIONAL BIOLOGY, 5(4).

By: D. Barua n, J. Faeder* & J. Haugh n

Ed(s): N. Kannan

MeSH headings : Adaptor Proteins, Signal Transducing / chemistry; Adaptor Proteins, Signal Transducing / metabolism; Binding Sites; Computer Simulation; Enzyme Activation; Janus Kinases / chemistry; Janus Kinases / metabolism; Models, Biological; Models, Chemical; Phosphorylation; Protein Binding; Signal Transduction / physiology
TL;DR: Analysis of the results revealed a unique mechanism whereby SH2-B and receptor dimers constitute a bipolar ‘clamp’ that stabilizes the active configuration of two Jak2 molecules in the same macro-complex. (via Semantic Scholar)
Sources: Web Of Science, ORCID, NC State University Libraries
Added: August 6, 2018

2009 journal article

Analysis of Reaction-Diffusion Systems with Anomalous Subdiffusion

BIOPHYSICAL JOURNAL, 97(2), 435–442.

By: J. Haugh n

MeSH headings : Cell Membrane / metabolism; Diffusion; Fluorescence Recovery After Photobleaching; Models, Biological; Time Factors
TL;DR: Two simple, conceptually extreme models of anomalous subdiffusion are used in the framework of Green's functions to demonstrate the solution of four reaction-diffusion problems that are well known in the biophysical context of signal transduction: fluorescence recovery after photobleaching, the Smolochowski limit for diffusion- controlled reactions in solution, the spatial range of a diffusing molecule with finite lifetime, and the collision coupling mechanism of diffusion-controlled reactions in two dimensions. (via Semantic Scholar)
Sources: Web Of Science, ORCID, NC State University Libraries
Added: August 6, 2018

2009 journal article

PI3K‐dependent cross‐talk interactions converge with Ras as quantifiable inputs integrated by Erk

Molecular Systems Biology, 5(1), 246.

By: C. Wang n, M. Cirit n & J. Haugh n

author keywords: kinetic model; mitogen-activated protein kinase; phosphatidylinositol 3-kinase; receptor tyrosine kinase; signal transduction
MeSH headings : Computational Biology; Extracellular Signal-Regulated MAP Kinases / metabolism; Humans; Phosphatidylinositol 3-Kinases / metabolism; Platelet-Derived Growth Factor / metabolism; Receptor Cross-Talk; Signal Transduction; ras Proteins / metabolism
TL;DR: Cross‐talk mechanisms in the platelet‐derived growth factor (PDGF) receptor signaling network, in which phosphoinositide 3‐kinase (PI3K) and Ras/extracellular signal‐regulated kinase (Erk) pathways are prominently activated, are elucidated. (via Semantic Scholar)
UN Sustainable Development Goal Categories
Sources: Crossref, ORCID, NC State University Libraries
Added: August 28, 2020

2009 journal article

Spontaneous phosphoinositide 3-kinase signaling dynamics drive spreading and random migration of fibroblasts

JOURNAL OF CELL SCIENCE, 122(3), 313–323.

By: M. Weiger n, C. Wang n, M. Krajcovic n, A. Melvin n, J. Rhoden n & J. Haugh n

author keywords: Cell migration; Phosphoinositide 3-kinase; Integrin; Fibronectin; Adhesion
MeSH headings : Actins / antagonists & inhibitors; Actins / metabolism; Animals; Chemotaxis / physiology; Cytochalasin D / pharmacology; Cytoskeleton / metabolism; Fibroblasts / cytology; Fibroblasts / metabolism; Fibroblasts / physiology; Focal Adhesion Protein-Tyrosine Kinases / metabolism; Mice; Phosphatidylinositol 3-Kinases / metabolism; Platelet-Derived Growth Factor / metabolism; Pseudopodia / metabolism; Receptors, Platelet-Derived Growth Factor / metabolism; Signal Transduction / physiology
TL;DR: Live-cell imaging using total internal reflection fluorescence (TIRF) microscopy revealed that, in the absence of soluble cues, 3′-phosphoinositides are enriched in a localized and dynamic fashion during active spreading and random migration of mouse fibroblasts on adhesive surfaces. (via Semantic Scholar)
Sources: Web Of Science, ORCID, NC State University Libraries
Added: August 6, 2018

2008 article

Biophysics - Cells get in shape for a crawl

Haugh, J. M. (2008, May 22). NATURE, Vol. 453, pp. 461–462.

By: J. Haugh*

MeSH headings : Actin Cytoskeleton / chemistry; Actin Cytoskeleton / metabolism; Animals; Cell Movement / physiology; Cell Shape / physiology; Epithelial Cells / cytology; Fishes; Models, Biological
TL;DR: A cell's shape changes as it moves along a surface, and the forward-thinking cytoskeletal elements are all for progress, but the conservative cell membrane keeps them under control by physically opposing their movement. (via Semantic Scholar)
UN Sustainable Development Goal Categories
14. Life Below Water (OpenAlex)
Sources: Web Of Science, ORCID, NC State University Libraries
Added: August 6, 2018

2008 journal article

Cell population-based model of dermal wound invasion with heterogeneous intracellular signaling properties

Cell Adhesion & Migration, 2(2), 137–145.

By: M. Monine* & J. Haugh n

author keywords: wound healing; chemotaxis; gradient sensing; mathematical model; stochastic; signal transduction; phosphoinositide 3-kinase; PDGF
MeSH headings : Cell Survival; Chemotaxis; Fibroblasts; Models, Biological; Phosphatidylinositol 3-Kinases / metabolism; Receptors, Platelet-Derived Growth Factor / metabolism; Signal Transduction; Skin / injuries; Skin / metabolism; Skin / pathology; Substrate Specificity
TL;DR: Analysis of the model suggests that the wound environment fosters the advancement of cells within the population that are better fit to migrate and/or proliferate in response to PDGF stimulation, and cell-to-cell variability results in a significantly higher rate of wound invasion. (via Semantic Scholar)
Source: ORCID
Added: July 13, 2021

2008 journal article

Combinatorial Signal Transduction Responses Mediated by Interleukin-2 and-4 Receptors in a Helper T-H2 Cell Line

CELLULAR AND MOLECULAR BIOENGINEERING, 1(2-3), 163–172.

By: K. Comfort n & J. Haugh n

author keywords: Cytokine receptor; Lymphocyte; Clonal expansion; Kinetic analysis; STAT; Phosphatidylinositol 3-kinase
TL;DR: It is found that IL-4 partially inhibits IL-2 receptor-mediated pathways (PI3K/Akt, Ras/Erk, and STAT5a/b) and does not prolong their transient kinetics, but this mode of antagonism, but not the effects on cell proliferation, is overcome at higher concentrations ofIL-2 that are sufficient to saturate the signaling responses. (via Semantic Scholar)
Sources: Web Of Science, ORCID, NC State University Libraries
Added: August 6, 2018

2008 journal article

Computational models of tandem Src homology 2 domain interactions and application to phosphoinositide 3-kinase

JOURNAL OF BIOLOGICAL CHEMISTRY, 283(12), 7338–7345.

By: D. Barua n, J. Faeder* & J. Haugh n

MeSH headings : Animals; Humans; Kinetics; Models, Biological; Phosphatidylinositol 3-Kinases / chemistry; Phosphatidylinositol 3-Kinases / metabolism; Receptor, Platelet-Derived Growth Factor beta / chemistry; Receptor, Platelet-Derived Growth Factor beta / metabolism; Surface Plasmon Resonance / methods; src Homology Domains / physiology
TL;DR: To analyze the interactions between tandem SH2 domains and bisphosphorylated peptides, detailed kinetic models were formulated and applied to the phosphoinositide 3-kinase p85 regulatory subunit/platelet- derived growth factor β-receptor system and found homodimerization of full-length p85 was found to be an alternative mechanism for high avidity binding to phosphorylated platelet-derived growth factor receptors. (via Semantic Scholar)
Sources: Web Of Science, ORCID, NC State University Libraries
Added: August 6, 2018

2008 journal article

First International Conference on Biomolecular Engineering (ICBE)

Biotechnology Progress, 24(1), 1–1.

By: M. DeLisa & J. Haugh

Source: NC State University Libraries
Added: August 6, 2018

2008 article

Mathematical Modelling of Biological Signaling Networks

Haugh, J. M. (2008, May). Wiley Encyclopedia of Chemical Biology.

By: J. Haugh n

TL;DR: The biological, chemical, and physical underpinnings of quantitative modeling has moved into the mainstream as a powerful tool for the analysis of cell signaling and its current applications and future challenges are presented. (via Semantic Scholar)
Source: ORCID
Added: July 13, 2021

2008 journal article

Signal transduction at point-blank range: Analysis of a spatial coupling mechanism for pathway crosstalk

BIOPHYSICAL JOURNAL, 95(5), 2172–2182.

By: M. Monine n & J. Haugh n

MeSH headings : Algorithms; Cell Membrane / metabolism; Computer Simulation; Models, Biological; Phosphatidylinositol 3-Kinases / metabolism; Receptor Cross-Talk; Signal Transduction; ras Guanine Nucleotide Exchange Factors / metabolism; ras Proteins / metabolism
TL;DR: The concept of spatial coupling is introduced, wherein simultaneous recruitment of different enzymes to the same receptor scaffold facilitates crosstalk between different signaling pathways through the local release and capture of activated signaling molecules. (via Semantic Scholar)
Sources: Web Of Science, ORCID, NC State University Libraries
Added: August 6, 2018

2007 personal communication

Membrane-binding/modification model of signaling protein activation and analysis of its control by cell morphology

Haugh, J. M. (2007, June 1).

By: J. Haugh*

MeSH headings : Cell Membrane / physiology; Eukaryotic Cells / cytology; Eukaryotic Cells / physiology; Intercellular Signaling Peptides and Proteins / metabolism; Intracellular Signaling Peptides and Proteins / metabolism; Signal Transduction / physiology
TL;DR: An important modification of this analysis is offered, recognizing that signaling proteins are not only activated at the plasma membrane but must first form complexes with signaling molecules that reside there, such as receptors and lipids. (via Semantic Scholar)
Sources: Web Of Science, ORCID, NC State University Libraries
Added: August 6, 2018

2007 journal article

Structure-based kinetic models of modular signaling protein function: Focus on Shp2

BIOPHYSICAL JOURNAL, 92(7), 2290–2300.

By: D. Barua n, J. Faeder* & J. Haugh n

MeSH headings : Computer Simulation; Enzyme Activation; Intracellular Signaling Peptides and Proteins / chemistry; Intracellular Signaling Peptides and Proteins / metabolism; Kinetics; Models, Biological; Models, Chemical; Models, Molecular; Phosphorylation; Protein Conformation; Protein Structure, Tertiary; Protein Tyrosine Phosphatase, Non-Receptor Type 11; Protein Tyrosine Phosphatases / chemistry; Protein Tyrosine Phosphatases / metabolism; Protein Tyrosine Phosphatases / ultrastructure; SH2 Domain-Containing Protein Tyrosine Phosphatases; Structure-Activity Relationship
TL;DR: To the knowledge, this is the first kinetic model to fully consider the modular, multifunctional structure of a signaling protein, and the computational approach should be generally applicable to other complex intermolecular interactions. (via Semantic Scholar)
Sources: Web Of Science, ORCID, NC State University Libraries
Added: August 6, 2018

2006 journal article

Deterministic model of dermal wound invasion incorporating receptor-mediated signal transduction and spatial gradient sensing

BIOPHYSICAL JOURNAL, 90(7), 2297–2308.

By: J. Haugh n

MeSH headings : Animals; Biophysics / methods; Cell Membrane / metabolism; Cell Movement; Cell Physiological Phenomena; Cell Proliferation; Chemotaxis; Diffusion; Endocytosis; Fibroblasts / metabolism; Kinetics; Mice; Models, Biological; Models, Statistical; Models, Theoretical; Phosphatidylinositol 3-Kinases / metabolism; Platelet-Derived Growth Factor / metabolism; Platelet-Derived Growth Factor / physiology; Receptors, Platelet-Derived Growth Factor / metabolism; Reproducibility of Results; Sensitivity and Specificity; Signal Transduction; Wound Healing
TL;DR: Analysis of the model suggests that PDGF receptor-mediated endocytosis and degradation of PDGF allows a constant PDGF concentration profile to be maintained at the leading front of the fibroblast density profile as it propagates, at a constant rate, into the clot. (via Semantic Scholar)
Sources: Web Of Science, ORCID, NC State University Libraries
Added: August 6, 2018

2006 journal article

Effectiveness factor for spatial gradient sensing in living cells

CHEMICAL ENGINEERING SCIENCE, 61(17), 5603–5611.

By: J. Haugh n & I. Schneider n

author keywords: cellular biology and engineering; kinetics; diffusion; mathematical modeling; chemotaxis; cell migration
TL;DR: It is concluded that the cell morphology and orientation with respect to the gradient can dictate whether messenger diffusion obliterates gradient sensing or has very little effect, and the effect of intracellular messenger diffusion on spatial gradient sensing to be quantified for individual cells. (via Semantic Scholar)
Sources: Web Of Science, ORCID, NC State University Libraries
Added: August 6, 2018

2006 journal article

Fast imaging of partially conductive linear cracks using impedance data

INVERSE PROBLEMS, 22(4), 1337–1358.

By: K. Bryan*, J. Haugh n & D. McCune*

UN Sustainable Development Goal Categories
Sources: Web Of Science, NC State University Libraries
Added: August 6, 2018

2006 journal article

Mechanisms of gradient sensing and chemotaxis - Conserved pathways, diverse regulation

CELL CYCLE, 5(11), 1130–1134.

By: I. Schneider n & J. Haugh*

author keywords: signal transduction; cell migration; phosphoinositide 3-kinase; Rho-family GTPases; mathematical modeling; diffusion; wound healing
MeSH headings : Animals; Chemotactic Factors / physiology; Chemotaxis / physiology; Fibroblasts / cytology; Humans; Wound Healing
TL;DR: This work quantitatively characterized a different gradient sensing system, that of platelet-derived growth factor-stimulated fibroblasts, an important component of dermal wound healing and led us to speculate on the diversity of gradient sensing mechanisms and their biological implications. (via Semantic Scholar)
Sources: Web Of Science, ORCID, NC State University Libraries
Added: August 6, 2018

2006 journal article

Quantitative model of Ras-phosphoinositide 3-kinase signalling cross-talk based on co-operative molecular assembly

BIOCHEMICAL JOURNAL, 393(1), 235–243.

By: H. Kaur n, C. Park n, J. Lewis n & J. Haugh n

author keywords: mathematical modelling; phosphoinositide 3-kinase (PI3K); platelet-derived growth factor (PDGF); Ras; receptor tyrosine kinase; signal transduction
MeSH headings : Animals; Mice; Models, Biological; NIH 3T3 Cells; Phosphatidylinositol 3-Kinases / metabolism; Proto-Oncogene Proteins c-akt / metabolism; Receptors, Platelet-Derived Growth Factor / metabolism; Signal Transduction; ras GTPase-Activating Proteins / metabolism
TL;DR: Experiments with platelet-derived growth factor-stimulated fibroblasts revealed that Ras apparently enhances the affinity of PI3K for receptors, which suggests that a ternary complex does indeed form, with the second step greatly enhanced through membrane localization and possibly allosteric effects. (via Semantic Scholar)
Sources: Web Of Science, ORCID, NC State University Libraries
Added: August 6, 2018

2005 journal article

Quantitative elucidation of a distinct spatial gradient-sensing mechanism in fibroblasts

JOURNAL OF CELL BIOLOGY, 171(5), 883–892.

By: I. Schneider n & J. Haugh n

MeSH headings : 3T3 Cells; Algorithms; Animals; Chemotaxis / physiology; Dictyostelium / cytology; Dictyostelium / physiology; Fibroblasts / physiology; Mice; Models, Biological; Neutrophils / physiology; Phosphatidylinositol 3-Kinases / metabolism; Platelet-Derived Growth Factor / metabolism; Signal Transduction
TL;DR: It is demonstrated that PDGF detection is governed by mechanisms that are fundamentally different from those in D. discoideum and neutrophils, which is consistent with a simpler system lacking the feedback loops that yield signal amplification and adaptation in amoeboid cells. (via Semantic Scholar)
Sources: Web Of Science, ORCID, NC State University Libraries
Added: August 6, 2018

2005 journal article

Reactions on cell membranes: Comparison of continuum theory and Brownian dynamics simulations

JOURNAL OF CHEMICAL PHYSICS, 123(7).

By: M. Monine n & J. Haugh n

MeSH headings : Algorithms; Biophysics / methods; Catalysis; Cell Membrane / metabolism; Chemistry, Physical / methods; Computer Simulation; Diffusion; Enzymes / chemistry; Models, Statistical; Models, Theoretical; Molecular Conformation; Signal Transduction; Static Electricity; Substrate Specificity
TL;DR: An efficient Brownian dynamics algorithm is developed that is especially suited for biochemical transduction of signals received by living cells and compared the simulation results with various continuum theories through prediction of effective enzymatic rate constant values. (via Semantic Scholar)
Sources: Web Of Science, ORCID, NC State University Libraries
Added: August 6, 2018

2005 journal article

Spatial analysis of 3 ' phosphoinositide signaling in living fibroblasts, III: Influence of cell morphology and morphological polarity

BIOPHYSICAL JOURNAL, 89(2), 1420–1430.

By: I. Schneider n, E. Parrish n & J. Haugh n

MeSH headings : Animals; Cell Polarity / physiology; Cell Size; Kinetics; Metabolic Clearance Rate; Mice; NIH 3T3 Cells; Phosphatidylinositol 3-Kinases / metabolism; Phosphatidylinositols / metabolism; Signal Transduction / physiology
TL;DR: It is found that although the 3' PI pattern is affected by irregular contact area shape, cell morphology alone cannot explain the presence of hot or cold spots, and the morphological polarity of the cell may bias 3'PI signaling to promote persistent migration in fibroblasts. (via Semantic Scholar)
Sources: Web Of Science, ORCID, NC State University Libraries
Added: August 6, 2018

2004 journal article

Mathematical model of human growth hormone (hGH)-stimulated cell proliferation explains the efficacy of hGH variants as receptor agonists or antagonists

BIOTECHNOLOGY PROGRESS, 20(5), 1337–1344.

By: J. Haugh n

MeSH headings : Cell Proliferation / drug effects; Computer Simulation; Dimerization; Dose-Response Relationship, Drug; Human Growth Hormone / genetics; Human Growth Hormone / pharmacology; Kinetics; Membrane Proteins / metabolism; Models, Biological; Protein Binding; Protein Transport / drug effects; Protein Transport / physiology; Signal Transduction / drug effects; Signal Transduction / physiology
TL;DR: A mathematical model of hGH‐stimulated cell signaling is posed, accounting not only for binding interactions at the cell surface but induction of receptor endocytosis and downregulation as well, and challenges the interpretations that have not considered receptor trafficking as a central regulatory mechanism in hGH signaling. (via Semantic Scholar)
UN Sustainable Development Goal Categories
Sources: Web Of Science, ORCID, NC State University Libraries
Added: August 6, 2018

2004 journal article

On the cross-regulation of protein tyrosine phosphatases and receptor tyrosine kinases in intracellular signaling

JOURNAL OF THEORETICAL BIOLOGY, 230(1), 119–132.

By: J. Haugh n, I. Schneider n & J. Lewis n

author keywords: signal transduction; receptor; phosphatase; kinase; phosphorylation
MeSH headings : Animals; Cell Membrane / metabolism; Models, Biological; Phosphorylation; Protein Tyrosine Phosphatases / metabolism; Signal Transduction / physiology; src-Family Kinases / metabolism
TL;DR: Receptor-PTP binding, in turn, is expected to influence the phosphorylation pattern of those receptors and proteins they associate with, and it is shown how PTPs might serve to co- or counter-regulate parallel pathways in a signaling network. (via Semantic Scholar)
UN Sustainable Development Goal Categories
Sources: Web Of Science, ORCID, NC State University Libraries
Added: August 6, 2018

2004 journal article

Spatial analysis of 3 ' phosphoinositide signaling in living fibroblasts: I. Uniform stimulation model and bounds on dimensionless groups

BIOPHYSICAL JOURNAL, 86(1), 589–598.

By: J. Haugh n & I. Schneider*

MeSH headings : Animals; Cells, Cultured; Computer Simulation; Diffusion; Fibroblasts / drug effects; Fibroblasts / metabolism; Humans; Microscopy, Fluorescence / methods; Models, Biological; Phosphatidylinositols / metabolism; Platelet-Derived Growth Factor / pharmacology; Reproducibility of Results; Sensitivity and Specificity; Signal Transduction / physiology; Tissue Distribution
TL;DR: A comprehensive model describing the dynamics of 3' phosphoinositides, lipid second messengers produced in the plasma membrane in response to stimulation of the PI 3-kinase signaling pathway is presented, as monitored in the cell-substratum contact area using total internal reflection fluorescence microscopy. (via Semantic Scholar)
Sources: Web Of Science, ORCID, NC State University Libraries
Added: August 6, 2018

2004 journal article

Spatial analysis of 3 ' phosphoinositide signaling in living fibroblasts: II. Parameter estimates for individual cells from experiments

BIOPHYSICAL JOURNAL, 86(1), 599–608.

By: I. Schneider n & J. Haugh*

MeSH headings : Cells, Cultured; Computer Simulation; Diffusion; Fibroblasts / drug effects; Fibroblasts / metabolism; Humans; Microscopy, Fluorescence / methods; Models, Biological; Phosphatidylinositols / metabolism; Platelet-Derived Growth Factor / pharmacology; Reproducibility of Results; Sensitivity and Specificity; Signal Transduction / physiology; Tissue Distribution
TL;DR: 3' PI turnover is not affected by PDGF receptor signaling in the authors' cells, allowing us to focus their attention on the regulation of 3' PI production as this system is studied further. (via Semantic Scholar)
Sources: Web Of Science, ORCID, NC State University Libraries
Added: August 6, 2018

2003 journal article

Kinetic analysis of platelet-derived growth factor receptor/phosphoinositide 3-kinase/Akt signaling in fibroblasts

JOURNAL OF BIOLOGICAL CHEMISTRY, 278(39), 37064–37072.

By: C. Park n, I. Schneider* & J. Haugh n

MeSH headings : 3T3 Cells; Animals; Fibroblasts / physiology; Kinetics; Mathematics; Mice; Models, Biological; Phosphatidylinositol 3-Kinases / physiology; Phosphorylation; Protein Serine-Threonine Kinases; Proto-Oncogene Proteins / physiology; Proto-Oncogene Proteins c-akt; Receptors, Platelet-Derived Growth Factor / physiology; Signal Transduction / physiology
TL;DR: It is found that PDGF receptor phosphorylation exhibits positive cooperativity with respect to PDGF concentration, and its kinetics are quantitatively consistent with a mechanism in which receptor dimerization is initially mediated by the association of two 1:1 PDGF/PDGF receptor complexes. (via Semantic Scholar)
Sources: Web Of Science, ORCID, NC State University Libraries
Added: August 6, 2018

2002 journal article

A unified model for signal transduction reactions in cellular membranes

BIOPHYSICAL JOURNAL, 82(2), 591–604.

By: J. Haugh n

MeSH headings : Animals; Biophysical Phenomena; Biophysics; Cell Membrane / metabolism; Guanosine Triphosphate / metabolism; Kinetics; Lipid Metabolism; Models, Biological; Models, Chemical; Models, Theoretical; Monomeric GTP-Binding Proteins / metabolism; Monte Carlo Method; Protein Binding; Signal Transduction; Substrate Specificity; Type C Phospholipases / metabolism
TL;DR: The generalized modeling framework is the first to combine reaction and diffusion limitations in enzyme action, the finite mean lifetime of receptor-enzyme complexes, reactions in the bulk membrane, and constitutive and receptor-mediated substrate insertion and is used to model two different signaling pathway types. (via Semantic Scholar)
Sources: Web Of Science, ORCID, NC State University Libraries
Added: August 6, 2018

2002 journal article

Active EGF receptors have limited access to PtdIns(4,5)P2 in endosomes: implications for phospholipase C and PI 3-kinase signaling

Journal of Cell Science.

Jason Haugh

Source: ORCID
Added: July 13, 2021

2002 journal article

Active EGF receptors have limited access to Ptdlns(4,5)P-2 in endosomes: implications for phospholipase C and PI 3-kinase signaling

Journal of Cell Science, 115(2), 303–310.

By: J. Haugh & T. Meyer

Source: NC State University Libraries
Added: August 6, 2018

2002 journal article

Localization of Receptor-Mediated Signal Transduction Pathways: The Inside Story

Molecular Interventions, 2(5), 292–307.

By: J. Haugh n

MeSH headings : Animals; Cell Membrane / metabolism; Enzyme Activation; ErbB Receptors / metabolism; Humans; Isoenzymes / metabolism; Membrane Microdomains; Phosphatidylinositol 3-Kinases / metabolism; Phosphatidylinositol 4,5-Diphosphate / metabolism; Phospholipase C gamma / metabolism; Receptor Protein-Tyrosine Kinases / metabolism; Signal Transduction / physiology; ras Proteins / metabolism
TL;DR: An exciting revelation is that internalized receptors extend some signaling activities but not others, suggesting that certain responses, such as cell motility, must be mediated at the cell surface. (via Semantic Scholar)
Source: ORCID
Added: July 13, 2021

2000 journal article

Mathematical modeling of epidermal growth factor receptor signaling through the phospholipase C pathway: Mechanistic insights and predictions for molecular interventions

BIOTECHNOLOGY AND BIOENGINEERING, 70(2), 225–238.

By: J. Haugh*, A. Wells* & D. Lauffenburger*

author keywords: signaling networks; mathematical model; intracellular processes; complexity
TL;DR: A simple mathematical model is formulated of a key signaling pathway required for regulated migration of fibroblasts and other cell types: activation of the intracellular enzyme phospholipase C mediated by epidermal growth factor receptor (EGFR) and a multitude of other transmembrane receptors. (via Semantic Scholar)
Sources: Web Of Science, NC State University Libraries
Added: August 6, 2018

2000 journal article

Mathematical modeling of epidermal growth factor receptor signaling through the phospholipase C pathway: Mechanistic insights and predictions for molecular interventions

Biotechnology and Bioengineering, 70(2), 225–238.

By: J. Haugh*, A. Wells* & D. Lauffenburger*

UN Sustainable Development Goal Categories
2. Zero Hunger (OpenAlex)
Source: ORCID
Added: July 13, 2021

2000 journal article

Spatial sensing in fibroblasts mediated by 3 ' phosphoinositides

JOURNAL OF CELL BIOLOGY, 151(6), 1269–1279.

By: J. Haugh*, F. Codazzi*, M. Teruel* & T. Meyer*

author keywords: chemotaxis; signal transduction; phosphatidylinositol 3-kinase; receptor protein-tyrosine kinases; platelet-derived growth factor
MeSH headings : 3T3 Cells; Animals; Cell Adhesion; Chemotaxis / physiology; Fibroblasts / physiology; Green Fluorescent Proteins; Luminescent Proteins; Mice; Microscopy, Confocal; Microscopy, Fluorescence; Models, Theoretical; Phosphatidylinositol 3-Kinases / metabolism; Phosphatidylinositols / metabolism; Platelet-Derived Growth Factor / metabolism; Protein Transport; Receptor Protein-Tyrosine Kinases / metabolism; Recombinant Fusion Proteins; Second Messenger Systems; Wound Healing / physiology
TL;DR: This study suggests that the tyrosine kinase-coupled directional movement of fibroblasts and their radial membrane activity are controlled by local generation and rapid degradation of 3′ PI second messengers. (via Semantic Scholar)
Sources: Web Of Science, ORCID, NC State University Libraries
Added: August 6, 2018

1999 journal article

Effect of Epidermal Growth Factor Receptor Internalization on Regulation of the Phospholipase C- 1 Signaling Pathway

Journal of Biological Chemistry, 274(13), 8958–8965.

By: J. Haugh*, K. Schooler*, A. Wells*, H. Wiley* & D. Lauffenburger*

MeSH headings : Animals; Cell Line; Endocytosis; Epidermal Growth Factor / pharmacology; ErbB Receptors / metabolism; Gene Expression Regulation, Enzymologic / genetics; Isoenzymes / metabolism; Lysosomes / metabolism; Mice; Phosphatidylinositol 4,5-Diphosphate / metabolism; Phospholipase C gamma; Phosphorylation; Phosphotyrosine / metabolism; Signal Transduction / genetics; Transforming Growth Factor alpha / pharmacology; Type C Phospholipases / metabolism
TL;DR: It is concluded that EGFR signaling through the PLC pathway is spatially restricted at a point between PLC-γ1 phosphorylation and PIP2 hydrolysis, perhaps because of limited access of EGFR-bound PLC -γ1 to its substrate in endocytic trafficking organelles. (via Semantic Scholar)
Source: ORCID
Added: July 13, 2021

1999 journal article

Internalized Epidermal Growth Factor Receptors Participate in the Activation of p21ras in Fibroblasts

Journal of Biological Chemistry, 274(48), 34350–34360.

By: J. Haugh*, A. Huang, H. Wiley*, A. Wells* & D. Lauffenburger*

MeSH headings : Adaptor Proteins, Signal Transducing; Adaptor Proteins, Vesicular Transport; Animals; Cell Compartmentation; Cells, Cultured; Endocytosis; ErbB Receptors / genetics; ErbB Receptors / metabolism; Fibroblasts / cytology; Fibroblasts / drug effects; Fibroblasts / metabolism; Flavonoids / pharmacology; Guanosine Diphosphate / metabolism; Guanosine Triphosphate / metabolism; Humans; MAP Kinase Kinase Kinase 1; MAP Kinase Kinase Kinases / antagonists & inhibitors; Models, Biological; Phosphorylation; Protein Binding; Protein Serine-Threonine Kinases; Proteins / metabolism; Proto-Oncogene Proteins p21(ras) / drug effects; Proto-Oncogene Proteins p21(ras) / metabolism; Recombinant Fusion Proteins / genetics; Recombinant Fusion Proteins / metabolism; Shc Signaling Adaptor Proteins; Src Homology 2 Domain-Containing, Transforming Protein 1; Tyrosine / metabolism; ras Guanine Nucleotide Exchange Factors / drug effects; ras Guanine Nucleotide Exchange Factors / metabolism
TL;DR: This work found that activated EGFR located at the cell surface and in internal compartments contribute equally to the membrane recruitment and tyrosine phosphorylation of Shc in NR6 fibroblasts expressing wild-type EGFR, which suggests a selective continuation of specific signaling activities and cessation of others upon receptor endocytosis. (via Semantic Scholar)
Source: ORCID
Added: July 13, 2021

1998 journal article

Analysis of Receptor Internalization as a Mechanism for Modulating Signal Transduction

Journal of Theoretical Biology, 195(2), 187–218.

By: J. Haugh* & D. Lauffenburger*

TL;DR: A generalized mathematical model describing the relationships among receptor, substrate, and target molecules is developed with the aim of gaining fundamental insights into one suggested control mechanism: endocytic trafficking-the rapid and induced internalization of ligated receptors and subsequent relocation to intracellular trafficking organelles. (via Semantic Scholar)
Source: ORCID
Added: July 13, 2021

1998 journal article

Scratching the (cell) surface: cytokine engineering for improved ligand/receptor trafficking dynamics

Chemistry & Biology, 5(10), R257–R263.

By: D. Lauffenburger*, E. Fallon & J. Haugh*

MeSH headings : Cytokines / genetics; Cytokines / metabolism; Epidermal Growth Factor / metabolism; Humans; Interleukin-2 / metabolism; Ligands; Protein Binding; Protein Engineering; Receptors, Cell Surface / metabolism
TL;DR: By combining protein-engineering techniques with studies of receptor trafficking and signaling, it might be possible to identify the ligand receptor-binding properties that should be sought. (via Semantic Scholar)
Source: ORCID
Added: July 13, 2021

1997 journal article

Physical modulation of intracellular signaling processes by locational regulation

Biophysical Journal, 72(5), 2014–2031.

By: J. Haugh* & D. Lauffenburger*

MeSH headings : Biophysical Phenomena; Biophysics; Cell Membrane / chemistry; Cell Membrane / metabolism; Cytosol / chemistry; Cytosol / metabolism; Models, Biological; Receptor Protein-Tyrosine Kinases / chemistry; Receptor Protein-Tyrosine Kinases / metabolism; Receptors, Cell Surface / chemistry; Receptors, Cell Surface / metabolism; Signal Transduction; Up-Regulation
TL;DR: This work analyzes the effect of relocation on the rate of association with a membrane-associated target and quantifies this effect as an enhancement factor E in terms of measurable parameters such as the number of available targets, molecular diffusivities, and intrinsic reaction rate constants. (via Semantic Scholar)
Source: ORCID
Added: July 13, 2021

article

Modeling Intracellular Signal Transduction Processes

Haugh, J. M., & Weiger, M. C. Chemical Biology, pp. 1061–1081.

By: J. Haugh n & M. Weiger*

Source: ORCID
Added: July 13, 2021

dataset

PI3K's Pivotal Role in Cell Migration

Welf, E., Ahmed, S., Johnson, H. E., Melvin, A. T., & Haugh, J. M. SciVee.

By: E. Welf, S. Ahmed, H. Johnson, A. Melvin & J. Haugh*

UN Sustainable Development Goal Categories
10. Reduced Inequalities (OpenAlex)
Source: ORCID
Added: July 13, 2021

Employment

Updated: February 14th, 2017 17:13

2000 - present

North Carolina State University Raleigh, NC, US
Professor Chemical & Biomolecular Engineering

Education

Updated: February 14th, 2017 17:11

1995 - 1999

Massachusetts Institute of Technology Cambridge, MA, US
PhD Chemical Engineering

1990 - 1994

North Carolina State University Raleigh, NC, US
BS Chemical Engineering

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