About

James Bear, PhD, is a professor in the Department of Cell Biology and Physiology at the University of North Carolina at Chapel Hill. His lab studies actin cytoskeletal dynamics, cell motility, and tumor invasion and metastasis. The research employs modern molecular perturbations such as gene knockouts, over-expression, and RNAi depletion to manipulate proteins involved in cell migration. Additionally, the lab investigates how tumor cells mis-regulate their motility during invasion and metastasis. A key technique used in his research is live-cell microscopy, which tracks proteins, protein complexes, and cell migration across various length and time scales to understand the impact on tissue architecture. The lab also utilizes microfabrication and microfluidic approaches to study cell migration in response to gradients of soluble growth factors, ECM proteins, and mechanical stiffness, providing insights into chemotaxis, haptotaxis, and durotaxis.

Research topics

• Biology
• Cell biology
• Biochemistry
• Chemistry
• Computer Science
• Ecology
• Neuroscience
• Genetics
• Anatomy

Selected publications

• Coro1B and Coro1C regulate lamellipodia dynamics and cell motility by tuning branched actin turnover

  The Journal of Cell Biology · 2022 · 29 citations

  Senior authorCorresponding
  • Cell biology
  • Biology
  • Biochemistry

  Actin filament dynamics must be precisely controlled in cells to execute behaviors such as vesicular trafficking, cytokinesis, and migration. Coronins are conserved actin-binding proteins that regulate several actin-dependent subcellular processes. Here, we describe a new conditional knockout cell line for two ubiquitous coronins, Coro1B and Coro1C. These coronins, which strongly co-localize with Arp2/3-branched actin, require Arp2/3 activity for proper subcellular localization. Coronin null cells have altered lamellipodial protrusion dynamics due to increased branched actin density and reduced actin turnover within lamellipodia, leading to defective haptotaxis. Surprisingly, excessive cofilin accumulates in coronin null lamellipodia, a result that is inconsistent with the current models of coronin-cofilin functional interaction. However, consistent with coronins playing a pro-cofilin role, coronin null cells have increased F-actin levels. Lastly, we demonstrate that the loss of coronins increases accompanied by an increase in cellular contractility. Together, our observations reveal that coronins are critical for proper turnover of branched actin networks and that decreased actin turnover leads to increased cellular contractility.

  DOI

• The principles of directed cell migration

  Nature Reviews Molecular Cell Biology · 2021 · 669 citations

  Senior authorCorresponding
  • Computer Science
  • Biology
  • Neuroscience
  DOI

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

  Biophysical Journal · 2021 · 16 citations

  • Cell biology
  • Biology
  • Chemistry
  PublisherOA PDFDOI

• Arp2/3 inactivation causes intervertebral disc and cartilage degeneration with dysregulated TonEBP-mediated osmoadaptation

  JCI Insight · 2020 · 30 citations

  • Cell biology
  • Biology
  • Chemistry

  Extracellular matrix and osmolarity influence the development and homeostasis of skeletal tissues through Rho GTPase-mediated alteration of the actin cytoskeleton. This study investigated whether the actin-branching Arp2/3 complex, a downstream effector of the Rho GTPases Cdc42 and Rac1, plays a critical role in maintaining the health of matrix-rich and osmotically loaded intervertebral discs and cartilage. Mice with constitutive intervertebral disc- and cartilage-specific deletion of the critical Arp2/3 subunit Arpc2 (Col2-Cre; Arpc2fl/fl) developed chondrodysplasia and spinal defects. Since these mice did not survive to adulthood, we generated mice with inducible Arpc2 deletion in disc and cartilage (Acan-CreERT2; Arpc2fl/fl). Inactivation of Arp2/3 at skeletal maturity resulted in growth plate closure, loss of proteoglycan content in articular cartilage, and degenerative changes in the intervertebral disc at 1 year of age. Chondrocytes with Arpc2 deletion showed compromised cell spreading on both collagen and fibronectin. Pharmacological inhibition of Cdc42 and Arp2/3 prevented the osmoadaptive transcription factor TonEBP/NFAT5 from recruiting cofactors in response to a hyperosmolarity challenge. Together, these findings suggest that Arp2/3 plays a critical role in cartilaginous tissues through the regulation of cell-extracellular matrix interactions and modulation of TonEBP-mediated osmoadaptation.

  DOI

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

  PLoS Computational Biology · 2020 · 8 citations

  • Cell biology
  • Biology
  • Chemistry

  Chemotaxis of fibroblasts and other mesenchymal cells is critical for embryonic development and wound healing. Fibroblast chemotaxis directed by a gradient of platelet-derived growth factor (PDGF) requires signaling through the phospholipase C (PLC)/protein kinase C (PKC) pathway. Diacylglycerol (DAG), the lipid product of PLC that activates conventional PKCs, is focally enriched at the up-gradient leading edge of fibroblasts responding to a shallow gradient of PDGF, signifying polarization. To explain the underlying mechanisms, we formulated reaction-diffusion models including as many as three putative feedback loops based on known biochemistry. These include the previously analyzed mechanism of substrate-buffering by myristoylated alanine-rich C kinase substrate (MARCKS) and two newly considered feedback loops involving the lipid, phosphatidic acid (PA). DAG kinases and phospholipase D, the enzymes that produce PA, are identified as key regulators in the models. Paradoxically, increasing DAG kinase activity can enhance the robustness of DAG/active PKC polarization with respect to chemoattractant concentration while decreasing their whole-cell levels. Finally, in simulations of wound invasion, efficient collective migration is achieved with thresholds for chemotaxis matching those of polarization in the reaction-diffusion models. This multi-scale modeling framework offers testable predictions to guide further study of signal transduction and cell behavior that affect mesenchymal chemotaxis.

  PublisherDOI

Recent grants

• NIH Grant R01GM083035

  NIH · $1.2M · 2014

• Cancer Genetics Research Program

  NIH · $80.2M · 1997–2027

• Mechanisms of mesenchymal chemotaxis

  NIH · $1.0M · 2014–2019

• The role of the Arp2/3 complex in cellular actin dynamics

  NIH · $1.5M · 2014–2019

• Systematic Analysis of the Actin Cytoskeleton and Directed Cell Migration

  NIH · $4.8M · 2019–2029

Frequent coauthors

• Sreeja B. Asokan

  105 shared

• Frank B. Gertler

  Massachusetts Institute of Technology

  69 shared

• Norman E. Sharpless

  51 shared

• Keefe T. Chan

  47 shared

• Jason M. Haugh

  North Carolina State University

  45 shared

• Douglas A. Lauffenburger

  Massachusetts Institute of Technology

  41 shared

• Madeleine J. Oudin

  40 shared

• Jeremy D. Rotty

  Unifor

  39 shared

Labs

• James Bear LabPI

Education

• B.S.

  Davidson College

• Ph.D.

  MIT

Awards & honors

• Phi Beta Kappa, Davidson College chapter (1993)
• ASCB Predoctoral Travel Award (1997)
• Anna Fuller Molecular Oncology Fellow (1999-2000)
• NIH NRSA Award (2000)
• Leukemia and Lymphoma Society Special Fellow (2001-04)

Similar researchers at University of North Carolina at Chapel Hill

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